abstracts

The Biology of Aging: 

Mechanisms and Intervention 

8 - 10 April 2010 

abstracts

Organization 

2 

German Society for Biochemistry and Molecular Biology 

Mörfelder Landstraße 125 

60598 Frankfurt am Main 

Germany 

Steering Commitee: 

Nikolaus Pfanner, Freiburg (President) 

Irmgard Sinning, Heidelberg (1st Vice-President) 

Alfred Wittinghofer, Dortmund (2nd Vice-President) 

Ulrich Brandt, Frankfurt am Main (Secretary-General) 

Wolfgang Trommer, Kaiserslautern (Treasurer) 

Head Office: 

Gabriele Holz (Finance) 

Tino Apel (IT and Support) 

Manfred Braun (Managing Director) 

www.gbm-online.de 

Technical Organization: 

GBM Head Office, Frankfurt am Main 

Christopher Schippers, CECAD Cologne 

Jens Brüning 

Thomas Langer 

Aleksandra Trifunovic 

University of Cologne 

CECAD Cologne 

at Institute for Genetics 

organization 

scientific committee 

CECAD is the Cluster of Excellence “Cellular Stress Responses 

in Aging-Associated Diseases” funded within the Excellence 

Initiative by German Federeal and State Governments

Content 

content page 

Organization 

Content/DOI 

Authors & Lecturers (in alphabetical order) 

Posternumbers 

Abstracts - Lectures (in chronological order) 

Abstracts - Poster 

Aging-Associated Diseases 

Caloric Restriction (Mechanisms and Mimetics) 

DNA Damage and Stem Cells 

Longevity and Insulin/IGF-1-Signaling 

Mitochondrial Control of Aging 

Other free Topics 

List of Participants 

Citation of abstracts / Digital Object Identifier (DOI) 

All meeting abstracts are indexed using the Digital Object Identifier (DOI). 

The Digital Object Identifier is an internationally accepted system for identifying and exchanging intellectual property 

in the digital environment and the standard reference system for electronic journals – for more information please 

see www.doi.org. 

You can use the DOI as reference for your abstracts as you did in the past years with the Volume and page number 

of a printed abstract magazine supplement. People can find the abstract e.g. searching the crossref.org database 

which links to the full abstract. 

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2 

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39 

41 

42 

45 

48 

57

Authors (in alphabetical order) 

author/lecturer info - poster number/lecture time - title 

Ackermann, Bianca info: 

A 6: HSF1-controlled and age-associated chaperone capacity in neurons and muscle cells of 

C. elegans 

Addicks, K info: Institut für Anatomie I, Universität zu Köln, Germany 

O 23: Novel role of the centrosomal protein TACC3 in nuclear pore complex assembly 

Agafonov, Dmitry info: Max Planck Institute for Biophysical Chemistry, Goettingen, Germany 

O 29: Functional Analysis of Silent Information Regulator-2 (SIR-2) Proteins in Caenorhabditis 

elegans 

Ahmadian, M. Reza info: Institut für Biochemie und Molekularbiologie II, Düsseldorf, Germany 

O 17: Mitotic spindle stress as a major trigger of premature senescence 

Alijotas-Reig, Jaume info: 

O 18: DNA damage signaling and ROS production in IL-1beta induced senescence in HUVEC 

Antebi, Adam info: Max-Planck-Institute for Biology of Ageing 

C 1: Hormonal Regulation of the Dietary Restriction Response in C. elegans 

Thu., 8 April, 15.00: Steroid hormone control of the reproductive longevity pathw ay 

Apkhazava, David info: 

C 6: Effect of caloric restriction on the catechin mediated life span extention in several C. 

elangans mutants 

Arndt, Verena info: 

A 1: Chaperone-assisted selective autophagy is essential for muscle proteostasis 

Asim, Mohammad info: Institute of Human Genetics and Anthropology, Jena University Hospital 

A 19: Inhibition of telomerase expression by androgens: A novel role of androgen receptor 

mutants for prostate cancer development 

Assfalg, Robin info: 

A 21: Cockayne syndrome mutations in TFIIH impair RNA polymerase I transcription 

Astridines, Aris info: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 

Philadelphia, USA 


Baird, Nathan info: 

Thu., 8 April, 9.20: Finding Specificity in the Genetics of Aging 

Baniahmad, Aria info: Institute of Human Genetics and Anthropology, Jena University Hospital 

A 14: Histone deacetylase inhibitors class I, II or III induce cellular senescence in 

neuroblastoma and prostate cancer 



Baniahmad, Aria info: 

A 13: Thyroid hormone induces cellular senescence in neuroblastoma cells 

Barikbin, Roja info: 

L 4: Ubiquitin Chain Editing Modulates Protein Homeostasis and Aging. 

Baris, Olivier info: 

M 10: Accumulation of mtDNA deletions during aging 

Bartelt, Alexander info: IBMII: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 

52, 20246 Hamburg, Germany 

A 8: BROWN ADIPOSE TISSUE IS A MAJOR DETERMINANT OF PLASMA CLEARANCE AND 

ORGAN UPTAKE OF TRIGLYCERIDE-RICH LIPOPROTEINS 

A 11: Characterization of PML Nuclear Bodies in Human Adipocytes 

Bartke, Andrzej info: Departments of Internal Medicine & Physiology, Southern Illinois University School of 

Medicine, Springfield, Illinois USA 

Thu., 8 April, 8.40: Grow th Hormone, Insuline and Aging 

Baumgart, Mario info: 

O 11: Identification and Quantification of microRNA Expression by High-Throughput- 

Sequencing in the short-lived Fish Nothobranchius furzeri 

Becker, Cord-Michael info: Institut für Biochemie, Friedrich-Alexander Universität Erlangen-Nürnberg 

A 9: Protein nitration and protein S-nitrosylation in retinal neurodegeneration 

4

author/lecturer 


info - poster number/lecture time - title 

Behl, Christian info: Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg 

University, Duesbergweg 6, 55099 Mainz, Germany 

A 6: HSF1-controlled and age-associated chaperone capacity in neurons and muscle cells of 

C. elegans 

A 10: Phenothiazines influence the dopaminergic cell death in Caenorhabditis elegans models 

of Parkinson’s disease 

A 15: Decline of cellular calcium efflux in in vitro models of Parkinson’s disease 

Belgardt, Bengt info: 

A 23: Hypothalamic and Pituitary JNK1 Signaling Coordinately Regulates Glucose Metabolism 

L 8: CERAMIDES IN THE DEVELOPMENT OF OBESITY-ASSOCIATED INSULIN- 

RESISTANCE 

C 7: Insulin signaling in SF1 neurons promotes diet-induced synaptic input reorganization of 

POMC-neurons and obesity development 

Benesova, Tereza info: 

M 6: Infrared-A radiation influences the skin fibroblast transcriptom: mechanisms and 

consequences for skin aging 

Beyreuther, Konrad info: 

A 2: Structure of the signaling domain of Alzheimer disease amyloid precursor protein in 

complex with Fe65-PTB2 

Bidlingmaier, Martin info: 

L 2: AGE-DEPENDENT LIVER REPOPULATION BY TRANSPLANTED HEPATOCYTES 

Bielohuby, Max info: 


Blaas, Leander info: 

O 21: Disruption of the GH-STAT5-IGF-1 axis causes hepatic fibrosis in the mdr2-/- mouse 

model of cholestasic liver disease 

Bloch, Wilhelm info: Department of Molecular and Cellular Sports Medicine, German Sports University, 50927 

Cologne 

M 9: Prooxidant Changes to the Matrix Drive Aging 

Blüher, Matthias info: Department of Medicine, University of Leipzig, D-04103 Leipzig, Germany 

A 24: Myeloid Cell-restricted Insulin Receptor Deficiency Protects Against Obesity-induced 

Inflammation and Systemic Insulin Resistance 

Böckers, Tobias info: 

C 2: Consequences of constitutive FoxO3 expression in neurons for neuronal development 

and adult neurogenesis 

Böhm, Michael info: Universitätsklinikum des Saarlandes, Innere Medizin III 

O 1: Long-term endurance exercise reduces senescence markers and telomere attrition in 

circulating leukocytes in professional athletes 

Bossinger, Olaf info: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, D-52074 Aachen, 

Germany 

O 10: Nanoparticles Induce Reproductive Senescence In Caenorhabditis elegans 

Bossinger, Olaf info: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, D-52074 Aachen, 

Germany 

L 9: Life span modulation in C. elegans: Analysis of epithelial genes 

Böttcher, Romy info: 

O 27: Genetic and biochemical evidence that excess levels of BCAA shorten Drosophila life 

span 

Braatz, Frank info: 

O 2: Correlation of human mesenchymal stem cell characteristics with donor age 

Brancati, Francesco info: IRCCS-CSS, San Giovanni Rotondo and CSS-Mendel Institute, 00198 Rome, Italy 

O 19: Mutations in PYCR1 Cause Cutis Laxa with Progeroid Features due to Reduced 

Mitochondrial Stress Resistance 

Brandt, Ulrich info: Molekulare Bioenergetik, Universitätsklinikum Frankfurt 

M 2: The role of the ubiquinone pool in modulating the superoxide production by the 

mitochondrial cytochrome bc1 complex 

Brendel, Alexander info: Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg 



5




Brenden, Heidi info: 

O 13: Neuraminidase 3 (Neu3) is critically involved in the initiation of the UVA stress response 

Breunig, Karin D. info: Universitaet Halle-Wittenberg, Institut fuer Biologie, 06099 Halle 

L 6: Comparison of the telomerase deletion response betw een tw o budding yeasts 

Brodesser, Susanne info: 

A 7: Role of Longevity Assurance (Lass) Genes in Membrane Senescence: Tissue-specific 

changes of ceramide species composition in aged mice 


Brodesser, Susanne info: 


RESISTANCE 

Broenneke, Hella S. info: 

M 8: Prohibitins control mitochondrial integrity and protect against neurodegeneration 

Brönneke, Hella S. info: 


Brüning, Jens info: Department of Mouse Genetics and Metabolism, Institute for Genetics, University of 

Cologne, D-50674 Cologne, Germany 





A 17: High fat diet and IL-6 cooperatively inhibit GSK-3β activity to provoke hepatocellular 

carcinoma development 

L 7: Repression of Foxo1 mediated signals rescues premature mortality in a mouse model of 

Alzheimer’s disease. 




Bruns, Oliver T. info: 

A 8: BROWN ADIPOSE TISSUE IS A MAJOR DETERMINANT OF PLASMA CLEARANCE 

AND ORGAN UPTAKE OF TRIGLYCERIDE-RICH LIPOPROTEINS 

Büchter, Christian info: Institute of Toxicology, Heinrich-Heine-University Düsseldorf, D-40225 Düsseldorf, 

Germany 


Bürkle, Alexander info: Molecular Toxikology Group, University of Konstanz 

A 5: Inflammatory and Age-related Pathologies in Mice w ith Ectopic Expression of Human 

PARP-1 

Bystrykh, Leonid info: 

Sat., 10 April, 12.25: Aging of hematopoietic stem cells: a program or noise? 

Calles, Christian info: 



Campisi, Judith info: 

Sat., 10 April, 11.15: DNA damage links inflammation, cancer and aging 

Canlon, Barbara info: Department of Physiology and Pharmacology, Karolinska Institutet 

Fri., 9 April, 16.35: The aging auditory system 

Carlile, Mark info: New castle University 

O 16: Gene regulation by natural antisense transcripts during sperm development and ageing: 

An example of antagonistic pleiotrophy? 

Casanova, Emilio info: Ludw ig-Boltzmann-Institut for Cancer Research, Vienna, Austria 



Cellerino, Alessandro info: 

M 7: Mitochondrial DNA copy number decreases upon ageing in the short-lived fish 

Nothobranchius furzeri 

O 11: Identification and Quantification of microRNA Expression by High-Throughput- 

Sequencing in the short-lived Fish Nothobranchius furzeri 

Chan, Danny info: Department of Biochemistry, the University of Hong Kong, Hong Kong, China 

A 22: Loss of ATP6V0A2 impairs intracellular trafficking and results in apoptotic cell death 

D 4: DNA damage-induced-replicative senescence in gerodermia osteodysplastica 

6




Chan, Hardy Wing Lee info: Department of Biochemistry, the University of Hong Kong, Hong Kong, China; Max-Planck- 

Institut für Molekulare Genetik, Research Group Mundlos, Berlin, Germany 



Charitidi, Konstantina info: Department of Physiology and Pharmacology, Karolinska Institutet 


Chaurasia, Bhagirath info: Department of Mouse Genetics and Metabolism, Institute for Genetics, University of 




Cheah, Kathy info: Department of Biochemistry, the University of Hong Kong, Hong Kong, China 


Chen, Min info: 

A 12: Protein homeostasis in intrinsic versus nanoparticle- induced senescence 

Christ, Bruno info: 


Cirstea, Ion C. info: Institut für Biochemie und Molekularbiologie II, Düsseldorf, Germany 


Clement, Albrecht M. info: 

A 6: HSF1-controlled and age-associated chaperone capacity in neurons and muscle cells of C. 

elegans 

Corrano, Andrea info: 


D. Sugawa, Michiru info: Physical Biochemistry, Department of Chemistry, Technische Universität Darmstadt, D- 

64287 Darmstadt, Germany; Clinical Neurobiology, Department of Psychiatry, CCM, Charité – 

Universitätsmedizin Berlin, D-10117 Berlin, Germany 

M 4: Supramolecular organisation of OxPhos complexes changes during ageing in various brain 

regions to a different extent 

Dallpiccola, Bruno info: IRCCS-CSS, San Giovanni Rotondo and CSS-Mendel Institute, 00198 Rome, Italy 



Dani, Diksha info: Physical Biochemistry, Department of Chemistry, Technische Universitaet Darmstadt, 

Petersenstrasse 22, D-64287 Darmstadt, Germany 

O 3: Anti-ageing mechanism of calorie restriction: Modulation of the mitoproteome and of ROS 

generation 

Daniel, Hannelore info: 

L 1: Altered signalling from germline to intestine pushes daf-2;pept-1 C. elegans into extreme 

longevity 

L 5: Hydroxyl group-rich flavonoids and aging processes in Caenorhabditis elegans. 

Daria, Deidre info: Department of Dermatology and Allergic Disease, Aging Research KFO 142, University of 

Ulm, Ulm, Germany, 

O 6: AGING ASSOCIATED HEMATOPOIETIC STEM CELL DEPOLARIZATION DEPENDS 

ON THE RHO FAMILY GTPASE CDC42 

Dawson, Ted M. info: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Departments of 

Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 

USA. 

Sat., 10 April, 9.35: Molecular Insights into Mitochondrial Dysfunction and Neurodegeneration in 

Parkinson’s Disease 

de Haan, Gerald info: 


Dencher, Norbert A. info: Physical Biochemistry, Department of Chemistry, Technische Universität Darmstadt, 

Petersenstraße 22, 64287 Darmstadt, Germany 


generation 

M 3: Age-dependend kynurenylation of a specific tryptophan residue in the ATP synthase alpha 

subunit of Podospora anserina 



C 3: Ageing and calorie restriction effect the mitochondrial proteome of rat heart 

Depping, Reinhard info: Department of Physiology, University of Lübeck, Germany 

O 5: The Role of oxygen signaling in oncogene-induced senescence 

7




Dexheimer, Verena info: 

O 2: Correlation of human mesenchymal stem cell characteristics w ith donor age 

Dhillon, Harveen info: 



Dick, Nikolaus info: 


Dillin, Andrew info: 


Dimopoulou, Aikaterini info: Institute of Medical Genetics, Charité Universitaetsmedizin Berlin, Germany 

O 19: Mutations in PYCR1 Cause Cutis Laxa w ith Progeroid Features due to Reduced 



Dong, Jijun info: 

O 24: Cellular organization of amyloids and oxidatively damaged proteins in yeast 

Dreiseidler, Michael info: 


Driscoll, Monica info: Primary Investigator 

O 14: MicroRNA modulators of C. elegans aging and healthspan 

Dröse, Stefan info: Molekulare Bioenergetik, Universitätsklinikum Frankfurt 

M 2: The role of the ubiquinone pool in modulating the superoxide production by the 

mitochondrial cytochrome bc1 complex 

Duerk, Heike info: 


elegans 

Dykstra, Brad info: 


E. Bäumer, Bastian info: Abteilung für Systembiochemie, Medizinische Fakultät der Ruhr-Universität Bochum, D- 

44780 Bochum, Germany 

O 4: The RING-finger peroxins Pex2p and Pex12p function as Ubiquitin-Ligases of the 

peroxisomal ubiquitination machinery 

Ebensing, Sabine info: 


Eferl, Robert info: 



Egerer, Johannes info: Max-Planck-Institut für Molekulare Genetik, Berlin, Germany 


Egerer, Johannes info: Charité Universitätsmedizin Berlin, Institute für Medizinische Genetik, Berlin, Germany; 

Max-Planck-Institut für Molekulare Genetik, Research Group Mundlos, Berlin, Germany 


Egger, Gerda info: 



Eissing, Leah info: IBMII: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 

Martinistraße 52, 20246 Hamburg, Germany 


El Magraoui, Fouzi info: Abteilung für Systembiochemie, Medizinische Fakultät der Ruhr-Universität Bochum, D- 




Elmquist, Joel info: 



Englert, Christoph info: 



Epstein, Sharon info: Department of Biochemistry, University of Geneva, Sw itzerland 

O 28: Short lifetime w ithout Ceramide synthase 3 

8




Erdmann, Ralf info: Abteilung für Systembiochemie, Medizinische Fakultät der Ruhr-Universität Bochum, D- 




Ernst, Marianne info: 



Ernst, Marianne B. info: 


Escande-Beillard, Nathalie info: Institute of Medical Biology, A*STAR, Singapore, Singapore 



Esslinger, Stephanie info: 


span 

Essmann, Frank info: Interfakultäres Institut für Biochemie (IFIB), Tübingen, Germany 


Esterbauer, Harald info: Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, 

Austria 



Fabrizio, Paola info: 

O 26: Genome-w ide screen in Saccharomyces cerevisiae identifies autophagy, biosynthetic, 

and tRNA methylation genes involved in life span extension 

Farinelli, Laurent info: Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute Göttingen, 

University of Göttingen, Max Planck Society, Grisebach Str 5, 37077 Goettingen, Germany. 

O 30: AN ALTERED HIPPOCAMPAL HISTONECODEIS ASSOCIATED WITH AGE- 

DEPENDENT MEMORY IMPAIRMENT 

Farsetti, Antonella info: Regina Elena Cancer Institute, Department of Experimental Oncology 



Felsner, Ingo info: 


Ferchiu, Florentina info: 

O 12: Redox Signalling Changes during Senescence in Human Dermal Fibroblasts 

Filippi, Marie-Dominique info: Division of Experimental Hematology, Department of Pediatrics, Cincinnati Children’s 

Hospital Medical Center, Cincinnati, OH 



Fischbach, Arthur info: Molecular Toxikology Group, University of Konstanz 

A 5: Inflammatory and Age-related Pathologies in Mice w ith Ectopic Expression of Human 

PARP-1 

Fischer, Andre info: Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute Göttingen, 


O 30: AN ALTERED HIPPOCAMPAL HISTONECODEIS ASSOCIATED WITH AGE- 


Fischer, Björn info: Institute of Medical Genetics, Charité Universitaetsmedizin Berlin, Germany 





Fischle, Wolfgang info: Max Planck Institute for Biophysical Chemistry, Goettingen, Germany 


elegans 

Florea, Ana-Maria info: 

O 15: Proteome analysis of senescence-associated protein changes in cultured human 

fibroblasts using a label-free mass spectrometry approach 

Florian, Maria Carolina info: Department of Dermatology and Allergic Disease, Aging Research KFO 142, University of 


O 6: AGING ASSOCIATED HEMATOPOIETIC STEM CELL DEPOLARIZATION DEPENDS ON THE 

RHO FAMILY GTPASE CDC42 

9




Förstemann, Klaus info: 


span 

Fraenzel, Benjamin info: 

C 5: The molecular mechanism of Sirtuin activation by resveratrol 

Frangakis, Achilleas info: 


Frenzel, Monika info: Physical Biochemistry, Department of Chemistry, Technische Universität Darmstadt, D- 

64287 Darmstadt, Germany; E-mail address: monika.frenzel@physbiochem.tu-darmstadt.de 



Füllekrug, Joachim info: University Hospital Heidelberg, Heidelberg, Germany 


Fürster, Tobias info: Universitätsklinikum des Saarlandes, Innere Medizin III 



Galbani, Abdulaye info: 

O 26: Genome-wide screen in Saccharomyces cerevisiae identifies autophagy, biosynthetic, 


Garadi Suresh, Harsha info: 


Geiger, Hartmut info: Department of Dermatology and Allergic Disease, Aging Research KFO 142, University of 




Gerisch, Birgit info: 

Thu., 8 April, 15.00: Steroid hormone control of the reproductive longevity pathway 

Gerlach, Claudia info: 


Gerrits, Alice info: 


Gertz, Melanie info: 


Gey, Claudia info: Center for Structural and Cell Biology in Medicine, University of Lübeck, Germany 


Giaever, Guri info: 



Girzalsky, Wolfgang info: Abteilung für Systembiochemie, Medizinische Fakultät der Ruhr-Universität Bochum, D- 




Göbel, Corinna info: Institut für Biochemie und Molekularbiologie II, Heinrich-Heine-Universität, Düsseldorf, 

Germany 


Gomez-Baldo, Laia info: Translational Research Laboratory, Bellvitge Institute for Biomedical Research, Barcelona 

08907, Spain 


Gorgas, Karin info: Medical Cell Biology, Institute for Anatomy, University of Heidelberg, Germany 

O 28: Short lifetime without Ceramide synthase 3 

Gorzelniak, Kerstin info: Institute of Laboratory Medicine and Pathobiochemistry, Charité Berlin, Germany 

D 1: Gene Expression Variations in Stress-Inducible Senescence and Replicative Senescence 

in Hutchinson-Gilford Progeria 

Goto, Sataro info: Juntendo University, Inbamura, Inbagun, Chiba, 270-1695 Japan 


Gracia Aranda, Natalia info: 


10




Graf, Michael info: 



Grasselli, Annalisa info: Regina Elena Cancer Institute, Department of Experimental Oncology 



Grether-Beck, Susanne info: IUF, Düsseldorf, Germany 


Grimm, Stefanie info: 

A 20: Lipofuscin-bound iron is a major intracellular source of oxidants: role in senescent cells 

Gröne, Hermann-Josef info: Cellular & Molecular Pathology, DKFZ, Heidelberg, Germany 


Groth, Marco info: 

O 11: Identification and Quantification of microRNA Expression by High-Throughput-Sequencing 

in the short-lived Fish Nothobranchius furzeri 

Gruber, Sabine info: 



Grünz, Gregor info: 


Grune, Tilman info: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstrasse 28, 

70593 Stuttgart, Germany 


O 25: Treatment of human dermal fibroblasts by water-filtered infrared A irradiation 

Guarente, Leonard P. info: 

Fri., 9 April, 11.15: SIRT1 controls neuro-endocrine signalling 

Gülow, Karsten info: 

A 4 : Oxidative Signaling in Aged T Lymphocytes 

Gumbold, Judith info: 



Hajieva, Parvana info: Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg 


A 10: Phenothiazines influence the dopaminergic cell death in Caenorhabditis elegans models 

of Parkinson’s disease 


Hampel, Brigitte info: Department of Mouse Genetics and Metabolism, Institute for Genetics, University of 







Hanenberg, Helmut info: Klinik für Kinder-Onkologie, -Hämatologie und -Klinische Immunologie, Düsseldorf, 

Germany 


Hanf, Benjamin info: Molecular Toxikology Group, University of Konstanz 

A 5: Inflammatory and Age-related Pathologies in Mice with Ectopic Expression of Human 

PARP-1 

Hartmann, Nils info: Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Beutenbergstr. 11, 07745 

Jena, Germany 



Hasson, Dan info: Department of Physiology and Pharmacology, Karolinska Institutet 


Heeren, Joerg info: 



Heeren, Jörg info: IBMII: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 

52, 20246 Hamburg, Germany 


11




Heestand, Bree info: Huffington Center on Aging, Baylor College of Medicine 

C 1: Hormonal Regulation of the Dietary Restriction Response in C. elegans 

Helenius, Ari info: ETH Zürich, Institute of Biochemistry, 8093 Zürich, Switzerland 

Fri., 9 April, 14.30: Otto Warburg Lecture: How animal viruses enter their host cells 

Hemmerich, Peter info: Department of Molecular Biology, Leibniz-Institute for Age-Research (FLI), Beutenbergstr. 

11, 07745 Jena, Germany 

D 2: Accumulation at the nuclear envelope identifies Annexin V as a potential biomarker of 

cellular senescence 

D 3: Senescing human cells accumulate PML at persisting DNA damage foci 

Hempel, Madlen info: 


Herrmann, Johannes info: 

A 18: Functions of mitochondrial Sod1 

O 20: Mitochondrial redox regulation 

Hess, Simon info: 




Hessenkemper, Wiebke info: 


A 14: Histone deacetylase inhibitors class I, II or III induce cellular senescence in 

neuroblastoma and prostate cancer 

Heumann, Rolf info: Ruhr-University Bochum, Faculty of Chemistry and Biochemistry, Department of Molecular 

Neurobiochemistry, Universitaetsstrasse 150, 44780 Bochum, Germany 

A 16: Involvement of voltage-dependent anion channel 1 (VDAC-1) in H-Ras-mediated 

neuroprotection? 

Higami, Yoshikazu info: Nagasaki University 


generation 

Hilf, Ricarda info: 

Thu., 8 April, 16.10: BayerSchering Pharma Thesis Prize: A Prokaryotic Perspective on 

Pentameric Ligand-Gated Ion Channels 

Hoeijmakers, Jan H.J. info: 

Sat., 10 April, 10.10: Quality control of DNA and the connection with aging 

Hoffmann, Christian info: Institut für Anatomie I, Universität zu Köln, Germany 


Hoffmann, Julia info: 

C 4: Starvation persistently changes expression profiles in fat storage organs of the fruit fly 

Drosophila 

Höhfeld, Jörg info: 


Höhn, Annika info: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstrasse 28, 




Holloszy, John info: 

Thu., 8 April, 11.35: Long-Term Calorie Restriction in Humans 

Honnen, Sebastian info: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, D-52074 Aachen, 

Germany 


Hoon, Shawn info: 



Hoppe, Thorsten info: 


Horvath, Tamas info: 



Horzowski, Eva info: 


12




Hu, Hao info: 


longevity 

Huber, R. info: 


Husch, Andreas info: 



Ibanez-Ventoso, Carolina info: Post-doc 


Iben, S. info: 


Iben, Sebastian info: 


Ibrahim, Saleh info: 

O 9: Outcome of the mitochondrial Atp8 mutation on betacell function and diabetessusceptibility 

Irlenbusch, Sigrid info: 


RESISTANCE 

Jähnicke, Reiner U. info: Klinik für Strahlentherapie und Radioonkologie, Düsseldorf, Germany 


Jang, Youngmok info: 

Fri., 9 April, 10.10: Mitochondrial dysfunction, oxidative stress and age-related skeletal muscle 

atrophy 

Janiesch, Christoph info: 


Jedrusik-Bode, Monika info: Max Planck Institute for Biophysical Chemistry, Goettingen, Germany 


elegans 

Jennemann, Richard info: Cellular & Molecular Pathology, DKFZ, Heidelberg, Germany 


Jochum, Marianne info: Division of Clinical Chemistry and Clinical Biochemistry in the Department of Surgery – 

City, Ludwig-Maximilians-University, Munich, Germany 

O 22: Cathepsin X-deficient fibroblasts undergo accelerated cellular senescence 

Johansson, Peter info: Department of Physiology and Pharmacology, Karolinska Institutet 


Jung, Tobias info: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstrasse 28, 




Kadowaki, Takashi info: 

Fri., 9 April, 16.00: Potential Role of Adiponectin and Adiponectin Receptors in Metabolic Fitness 

and Logevity 

Kaeberlein, Matt info: 

Thu., 8 April, 9.20: Molecular mechanisms linking diet, disease, and aging. 

Kahn, C. Ronald info: Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston 



Kampkötter, Andreas info: Bayer Animal Health GmbH, Research and Development, D-40789 Leverkusen, Germany 


Kandhaya -Pillai, Renuka info: 


Kashkar, Hamid info: 



Kayserili, Hülya info: Medical Genetics Department, Istanbul Medical Faculty, University of Istanbul, Turkey 



13




Kenner, Lukas info: Clinical Institute of Pathology, Medical University of Vienna, Austria 

O 21: Disruption of the GH-STAT5-IGF-1 axis causes hepatic fibrosis in the mdr2-/- mouse model 

of cholestasic liver disease 

Kenyon, Cynthia info: 

Thu., 8 April, 19.00: Feodor Lynen Lecture: From w orms to mammals: genes that can increase 

lifespan 

Kern, Andreas info: Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg 

University, Duesbergw eg 6, 55099 Mainz, Germany 


elegans 

A 10: Phenothiazines influence the dopaminergic cell death in Caenorhabditis elegans models of 

Parkinson’s disease 

Kevei, Eva info: 


Klement, Karolin info: Leibniz Institute for Age Research, Fritz Lipmann Institute, Beutenbergstraße 11, 07745 Jena 

D 2: Accumulation at the nuclear envelope identifies Annexin V as a potential biomarker of cellular 

senescence 

Kletke, Anja info: Institut für Biochemie und Molekularbiologie II, Düsseldorf, Germany 


Kloeckener, Tim info: 



Klöppel, Tina info: 


Kloppenburg, Peter info: 


C 7: Insulin signaling in SF1 neurons promotes diet-induced synaptic input reorganization of POMCneurons 

and obesity development 

Koch, Christiane info: 


Kochanek, Stefan info: 


Kohn, Matthias info: Department of Dermatology and Allergic Diseases, University of Ulm, 89081 Ulm 


Kohne, Zippora info: 


Köhrer, Karl info: Biomedizinisches Forschungs-zentrum (BMFZ), Düsseldorf, Germany 


Kojer, Kerstin info: 


Kolanczyk, Mateusz info: 1Max Planck Institute for Molecular Genetics, Development & Disease Group/2Institute for 

Medical Genetics, Charitè, Universitätsmedizin Berlin, Email: kolanshy@molgen.mpg.de 

O 31: Targeted inactivation of the mouse NOA1 gene 

Komatsu, Toshimitsu info: Nagasaki University 


generation 

Kornak, Uw e info: Charité Universitätsmedizin Berlin, Institute für Medizinische Genetik, Berlin, Germany; Max- 

Planck-Institut für Molekulare Genetik, Research Group Mundlos, Berlin, Germany 





Kornfeld, Jan-Wilhelm info: Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, 

Germany 



Korte, Birgit info: 

O 15: Proteome analysis of senescence-associated protein changes in cultured human fibroblasts 

using a label-free mass spectrometry approach 

Korw itz, Anne info: 


14




Krammer, Peter H. info: 


Kraus, Steffen info: Division of Clinical Chemistry and Clinical Biochemistry in the Department of Surgery – City, 

Ludwig-Maximilians-University, Munich, Germany 


Krause, Frank info: Physical Biochemistry, Department of Chemistry, Technische Universitaet Darmstadt, 



generation 

Krone, Wilhelm info: 



Krönke, Martin info: 



Krutmann, Jean info: 




Kuck, Fabian info: Institut für Biochemie und Molekularbiologie II, Düsseldorf, Germany 


Kuhlbrodt, Kirsten info: 


Kuhlmann, Katja info: 

A 3: Identification of APP/FE65/TIP60-complex dependent pathways by using a comprehensive 

proteomic approach 

Kurzchalia, Teimo info: mpi-cbg, Dresden, Germany 


Kuteykin-Teplyakov, Konstantin info: present address: Ludwig-Maximilians-University, Center for Neuropathology, Feodor-Lynen- 

Strasse 23, 81377 Muenchen, Germany 



Kyrylenko, Sergiy info: 


A 14: Histone deacetylase inhibitors class I, II or III induce cellular senescence in neuroblastoma 

and prostate cancer 

Lakshminarasimhan, Mahadevan info: 


Langer, Thomas info: Institute for Genetics, Centre for Molecular Medicine (CMMC) and Cologne Excellence 

Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of 

Cologne, 50674 Cologne, Germany; Max-Planck-Institute for the Biology of Agin 


Lars, Paeger info: 



Larsson, Nils-Göran info: 

Fri., 9 April, 09.00: Regulation of mtDNA expression 

Lasch, Katrin info: 


longevity 

Laufs, Ulrich info: Universitätsklinikum des Saarlandes, Innere Medizin III 



Lebedev, Anton info: 


Lee, Hane info: Department of Human Genetics, David Geffen School of Medicine, University of California, 

Los Angeles, Los Angeles, USA 



15




Li, Yun info: Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany 



Lindecke, Antje info: Biomedizinisches Forschungs-zentrum (BMFZ), Düsseldorf, Germany 


Lindquist, Susan info: 


Link, Sebastian info: 



Liu, Yuhong info: 


atrophy 

Longo, Valter info: 

O 26: Genome-w ide screen in Saccharomyces cerevisiae identifies autophagy, biosynthetic, and 

tRNA methylation genes involved in life span extension 

Longo, Valter D. info: 

Thu., 8 April, 15.35: Grow th signaling pathw ays and aging: from yeast to humans 

Looße, Christina info: 

A 3: Identification of APP/FE65/TIP60-complex dependent pathw ays by using a comprehensive 


Lorenz, Viola info: 


Lorenz, Viola info: 



Low ell, Bradford info: 

C 7: Insulin signaling in SF1 neurons promotes diet-induced synaptic input reorganization of POMCneurons 

and obesity development 

Ludolph, Albert C. info: Department of Neurology, University of Ulm, 89081 Ulm 


Lück, Claudia info: 



Macaluso, Filippina info: 



Machlitt, Caroline info: 

L 6: Comparison of the telomerase deletion response betw een tw o budding yeasts 

Maier, Harald info: 

C 2: Consequences of constitutive FoxO3 expression in neurons for neuronal development and 

adult neurogenesis 

Mair, Markus info: 



Mair, William info: 


Maity, P. info: 


Maity, Pallab info: Department of Dermatology and Allergic Diseases, University of Ulm, 89081 Ulm, Germany 


Majora, Marc info: 


Mangerich, Asw in info: Molecular Toxikology Group, University of Konstanz 

A 5: Inflammatory and Age-related Pathologies in Mice w ith Ectopic Expression of Human PARP-1 

Mann, Carl inf o: IBITEC-S, CEA, France 


Marcus, Katrin info: 



16




Martinelli, Paola info: 


Mauer, Jan info: 


Mauer, Jan info: Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, 

D-50674 Cologne, Germany 



Mayer, Doris info: 

L 3: Mechanism of the mitogenic effect of the insulin analogue glargine 

Mayer, Sabine info: 

O 8: Signal transduction of pregnenolone sulfate in insulinoma cells: Activation of Egr-1 

expression involving voltage-gated Ca2+ channels, ERK and ternary complex factors 

McCaffery, J. Michael info: 


Melle, Christian info: Core Unit Chipapplikationen (CUCA), Institut für Humangenetik und Anthropologie, 

Universitätsklinikum Jena, 07745 Jena 


senescence 

Meltser, Inna info: Department of Physiology and Pharmacology, Karolinska Institutet 


Merkel, Martin info: 



Merkwirth, Carsten info: Institute for Genetics, Centre for Molecular Medicine (CMMC) and Cologne Excellence 

Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of 

Cologne, 50674 Cologne, Germany. 


Meyer, Helmut info: 



Meyer, Helmut E. info: 



Michels, Christine info: 


Mikulits, Wolfgang info: Department of Medicine I, Institute of Cancer Research, Medical University of Vienna (MUW), 

Austria 



Miller, Richard info: Dept. of Pathology and Geriatrics Center, University of Michigan 

Thu., 8 April, 11.00: Multiple Approaches to Lifespan Extension in Mice 

Miro-Mur, Francesc info: 


Mocko, Justyna B. info: Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg 




Modlich, Olga info: Institut für Biochemie und Molekularbiologie II, Düsseldorf, Germany 


Moehren, Udo info: Institute of Human Genetics and Anthropology, Jena University Hospital 



Moll, Lorna info: 



17




Moosmann, Bernd info: Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg 


M 5: Longevity, Aerobicity and the Differential Loss of Cysteine in Respiratory Chain Complexes 



Moraes, Carlos info: 

M 1: Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease 

during aging 

Moriggl, Richard info: 



Moser, Natascha info: 


Müller, Isabelle info: 

O 7: Regulation of AP-1 activity in glucose-stimulated insulinoma cells 



Müller, Sebastian info: 


Müller, Thorsten info: 



Münch, Sandra info: Department of Molecular Biology, Leibniz-Institute for Age-Research (FLI), Beutenbergstr. 11, 

07745 Jena, Germany 


Mundlos, Stefan info: Charité Universitätsmedizin Berlin, Institute für Medizinische Genetik, Berlin, Germany; Max- 

Planck-Institut für Molekulare Genetik, Research Group Mundlos, Berlin, Germany 





Musteanu, Monica info: 



Nägler, Dorit info: Division of Clinical Chemistry and Clinical Biochemistry in the Department of Surgery – City, 

Ludwig-Maximilians-University, Munich, Germany 


Nanni, Simona info: Regina Elena Cancer Institute, Department of Experimental Oncology 



Neuhaus, Johannes info: 


Neumann, Sebastian info: Ruhr-University Bochum, Faculty of Chemistry and Biochemistry, Department of Molecular 

Neurobiochemistry, Universitaetsstrasse 150, 44780 Bochum, Germany 



Nickel, Walter info: BZH, University of Heidelberg, Germany 


Nislow, Corey info: 

O 26: Genome-wide screen in Saccharomyces cerevisiae identifies autophagy, biosynthetic, and 


Niu, Xianzhi info: Department of Physiology and Pharmacology, Karolinska Institutet 


Norgauer, Johannes info: Universitätsklinikum Jena Klinik f. Hautkrankheiten, Erfurter Straße 35, 07743 Jena 


senescence 

Nozadze, Maia info: 

C 6: Effect of caloric restriction on the catechin mediated life span extention in several C. 

elangans mutants 

18




Nürnberg, Bernd info: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Tübingen, Germany, 

Tübingen, Germany 


Nürnberg, Peter info: Cologne Center for Genomics (CCG), Universität zu Köln, Germany 



Nüsseler, Elke info: 


Nystrom, Thomas info: 

Fri., 9 April, 11.50: Unequal inheritance and retrograde transport of protein aggregates - a means 

to rejuvenation in yeast 

Olthof, Sandra info: 


Osiewacz, Heinz D. info: 



Pal, Martin info: 


Panowski, Siler info: 


Papaioannou, Maria info: Institute of Human Genetics and Anthropology, Jena University Hospital 



Peleg, Shahaf info: Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute Göttingen, 


O 30: AN ALTERED HIPPOCAMPAL HISTONE CODE IS ASSOCIATED WITH AGE- 


Penninger, Josef info: Institute of Molecular Biology of the Austrian Academy of Sciences (IMBA), Vienna, Austria 



Penninger, Josef M. info: 

Fri., 9 April, 17.10: From a little mutant mouse to human medicine for bone loss 

Piazena, Helmut info: Klinik für Psychiatrie und Psychotherapie, AG Medizinische Photobiologie, Charité- 

Universitätsmedizin Berlin, Charité-Platz 1, 10117 Berlin, Germany 


Piechura, Heike info: 



Piekorz, Roland info: Institut für Biochemie und Molekularbiologie II, Heinrich-Heine-Universität, Düsseldorf, 

Germany 


Piekorz, Roland P. info: Institut für Biochemie und Molekularbiologie II, Düsseldorf, Germany 


Platta, Harald W. info: Abteilung für Systembiochemie, Medizinische Fakultät der Ruhr-Universität Bochum, 44780 

Bochum, Germany 



Platzer, Matthias info: 



O 11: Identification and Quantification of microRNA Expression by High-Throughput-Sequencing in 

the short-lived Fish Nothobranchius furzeri 

Plum, Leona info: Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, 

D-50674 Cologne, Germany 



Pluskota, Adam info: 


19




Poetsch, Ansgar info: 



Pongratz, Carola info: 



Popp, Oliver info: Molecular Toxikology Group, University of Konstanz 

A 5: Inflammatory and Age-related Pathologies in Mice with Ectopic Expression of Human PARP-1 

Prade, Ina info: Institute of Human Genetics and Anthropology, Jena University Hospital 



Pujana, Miguel info: Translational Research Laboratory, Bellvitge Institute for Biomedical Research, Barcelona 

08907, Spain 


Rabionet, Mariona info: Cellular & Molecular Pathology, DKFZ, Heidelberg, Germany 


Radzimanowski, Jens info: 

A 2: Structure of the signaling domain of Alzheimer disease amyloid precursor protein in complex 

with Fe65-PTB2 

Reeb, Christina A. info: Institute of Human Genetics and Anthropology, Jena University Hospital 



Reichwald, Kathrin info: 



Reifenberger, Guido info: 



Reinheckel, Thomas info: Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University, Freiburg, 

Germany 


Reunert, Janine info: Department of Pediatrics, University Münster, Germany 

D 1: Gene Expression Variations in Stress-Inducible Senescence and Replicative Senescence in 

Hutchinson-Gilford Progeria 

Reversade, Bruno info: Institute of Medical Biology, A*STAR, Singapore, Singapore 



Rexroth, Sascha info: 



Richter, Wiltrud info: 


Riemer, Jan info: jan.riemer@biologie.uni-kl.de 



Riezman, Howard info: Department of Biochemistry, University of Geneva, Switzerland 


Ritsema, Martha info: 


Robertson, Stephen info: Department of Paediatrics and Child Health, University of Otago, Dunedin, New Zealand 



Rödiger, Julia info: 



Roeder, Thomas info: 


Drosophila 

Roell, Daniela info: Institute of Human Genetics and Anthropology, Jena University Hospital 



20




Roepstorff, P. info: 


Rogowska-Wrezescinska, Adelina info: 


Rojewski, Mark info: Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, University of Ulm, 

Germany 

O 6: AGING ASSOCIATED HEMATOPOIETIC STEM CELL DEPOLARIZATION DEPENDS ON 

THE RHO FAMILY GTPASE CDC42 

Romey, Renja info: 


Drosophila 

Rommelspacher, Hans info: Clinical Neurobiology, Department of Psychiatry, CCM, Charité – Universitätsmedizin Berlin, 

10117 Berlin, Germany 



Rossi, Susana info: 


during aging 

Rotundo, Richard info: 


during aging 

Rubio-Aliaga, Isabel info: 


longevity 

Rudolph, K. Lenhard info: Max-Planck-Research-Department for Stem Cell Aging and Institute of Molecular Medicine, 

Ulm University, Germany. Email: Lenhard Rudolph@uni-ulm.de 

Sat., 10 April, 11.50: Telomere Dysfunction, DNA Damage, and Stem Cell Aging 



Rugarli, Elena I. info: Division of Biochemistry and Genetics, Istituto Neurologico C, Besta, Milan, Italy. 


Saibil, Helen info: 


Samatov, Timur info: Max Planck Institute for Biophysical Chemistry, Goettingen, Germany 


elegans 

Sananbenesi, Farahnaz info: Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute Göttingen, 




Sandhoff, Roger info: Cellular & Molecular Pathology, DKFZ, Heidelberg, Germany 


Sante, Lea info: 


Sass, Sabine info: 


Sattler, Michael info: 



Schäfer, Eva R. info: 



Scharffetter-Kochanek, Karin info: Department of Dermatology and Allergic Disease, Aging Research KFO 142, University of 

Ulm, Ulm, Germany 






Schauss, Astrid C. info: 


21




Scheel, Martin info: Institute of Laboratory Medicine, University Münster, Germany 

D 1: Gene Expression Variations in Stress-Inducible Senescence and Replicative Senescence in 

Hutchinson-Gilford Progeria 

Schelling, Adrian info: 


Schilbach, Katharina info: 



Schindeldecker, Mario info: 

M 5: Longevity, Aerobicity and the Differential Loss of Cysteine in Respiratory Chain Complexes 

Schips, Tobias info: 



Schirmacher, Peter info: 



Schlee, Daniel info: Abteilung für Systembiochemie, Medizinische Fakultät der Ruhr-Universität Bochum, 44780 

Bochum, Germany 



Schlicker, Christine info: 


Schmidt, Stephan info: Institut für Biochemie und Molekularbiologie II, Heinrich-Heine-Universität, Düsseldorf, 

Germany 



Schmidt-Straßburger, Uta info: 



Schmidt-von Kegler, Mareen info: Max Planck Institute for Molecular Genetics, Berlin, Germany 



Schnabel, Anke info: 



Schneider, Leonid info: Institut für Biochemie und Molekularbiologie II, Düsseldorf, Germany 


Schneider, Maren info: 



Schneller, Doris info: 



Schnoelzer, Martina info: Functional Proteome Analysis, German Cancer Research Center (DKFZ) 


generation 

Schokraie, Elham info: Functional Proteome Analysis, German Cancer Research Center (DKFZ) 


generation 

Schramek, Daniel info: 



Schramm, Hans J. info: MPI Biochemie, Martinsried 

A 25: “Dimerization inhibitors” of HIV-1 protease: from interface targeting peptides to triterpenes 

Schramm, Wolfgang info: LMU Munich 

A 25: “Dimerization inhibitors” of HIV-1 protease: from interface targeting peptides to triterpenes 

Schreuder, Jaring info: 


22




Schrezenmeier, Hubert info: Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, University of Ulm, 

Germany 



Schröder, Hannsjörg info: 


Schröder, Verena info: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, D-52074 Aachen, 

Germany 


Schroeder, Peter info: 



Schrötter, Andreas info: 



Schubert, Markus info: 



Schülke, Markus info: Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité 

Universitaetsmedizin Berlin, Germany 



Schulze-Osthoff, Klaus info: Interfakultäres Institut für Biochemie (IFIB), Tübingen, Germany 


Schumbrutzki, Cornelia info: 



Schwalb, Björn info: 

O 27: Genetic and biochemical evidence that excess levels of BCAA shorten Drosophila life span 

Schwartz Jr, Simo info: 


Seeger, Jens info: 



Seemann, Petra info: Berlin-Brandenburg Center for Regenerative Therapies, Charité Universitaetsmedizin Berlin, 

Germany 



Segref, Alexandra info: 


Shah, Mitalie info: Research Associate 


Shamalnasab, Mehrnaz info: 

O 26: Genome-wide screen in Saccharomyces cerevisiae identifies autophagy, biosynthetic, and 


Shimokawa, Isao info: Nagasaki University 


generation 

Shukla, Ashish info: 

L 3: Mechanism of the mitogenic effect of the insulin analogue glargine 

Simon, Bernd info: 



Sindrilaru, Anca info: 


Singer, Anja Lena info: 


Sinning, Irmgard info: 



23




Sirma, Hüseyin info: Department for General Virology, Heinrich-Pette-Institute for Experimental Virology and 

Immunology, Martinistraße 52, 20246 Hamburg, Germany 


Sitek, Barbara info: 



Spanier, Britta info: 


longevity 


Spiegelman, Bruce info: 


during aging 

Spohn, Gabriele info: 


Steegborn, Clemens info: 


Stilling, Roman info: Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute Göttingen, 




Stock, Peggy info: 


Stühler, Kai info: 



Sugawa, Michiru info: Physical Biochemistry, Department of Chemistry, Technische Universitaet Darmstadt, 



generation 

Sugawa, Michiru info: Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany 


Swan, Dan info: Newcastle University 

O 16: Gene regulation by natural antisense transcripts during sperm development and ageing: 

An example of antagonistic pleiotrophy? 

Tanzi, Rudolph info: 

Sat., 10 April, 9.00: Clues to the causes of Alzheimer's Disease from genetics 

Tawo, Riga info: 


Terzibasi, Eva info: 



Thiel, Gerald info: 

O 7: Regulation of AP-1 activity in glucose-stimulated insulinoma cells 



Thilmany, Sandra info: Physical Biochemistry, Department of Chemistry, Technische Universität Darmstadt, 

Petersenstraße 22, 64287 Darmstadt, Germany 


Tiedge, Markus info: 


Tomaschewski, Jana info: 


Toth, Marton info: Post Doc 


Toussaint, O. info: 


Trauner, Michael info: Clinical Institute of Pathology, Medical University of Vienna, Austria 



24




Treiber, N. info: 


Treiber, Nicolai info: Department of Dermatology and Allergic Diseases, University of Ulm, 89081 Ulm 


Tresch, Achim info: 

O 27: Genetic and biochemical evidence that excess levels of BCAA shorten Drosophila life span 

Trifunovic, Aleksandra info: 

Thu., 8 April, 12.10: How much mtDNA mutations contribute to ageing: lessons from mtDNA 

mutator mice 

Tyedmers, Jens info: 


Ushmorova, Nina info: 



Van Maldergem, Lionel info: Germany. 31 Centre de génétique humaine, CHU du Sart-Tilman, Université de Liège, 

B-4000 Liège 



Van Remmen, Holly info: 


atrophy 

van Zijl, Franziska info: 

O 21: Disruption of the GH-STAT5-IGF-1 axis causes hepatic fibrosis in the mdr2-/mouse 


von Mikecz, Anna info: 



Vora, Mehul info: Graduate Student 


Voss, Reinhard info: Institute of Laboratory Medicine, University Münster, Germany 

D 1: Gene Expression Variations in Stress-Inducible Senescence and Replicative 

Senescence in Hutchinson-Gilford Progeria 

Waldera, Daniel info: 



Walli, Rehab info: 


Walter, Michael info: Institute of Laboratory Medicine and Pathobiochemistry, Charité Berlin, Germany 

D 1: Gene Expression Variations in Stress-Inducible Senescence and Replicative 

Senescence in Hutchinson-Gilford Progeria 

Warnken, Uw e info: Functional Proteome Analysis, German Cancer Research Center (DKFZ) 

O 3: Anti-ageing mechanism of calorie restriction: Modulation of the mitoproteome and of 

ROS generation 

Warscheid, Bettina info: 



Wei, Min info: 

O 26: Genome-w ide screen in Saccharomyces cerevisiae identifies autophagy, 

biosynthetic, and tRNA methylation genes involved in life span extension 

Weidtkamp-Peters, Stefanie info: Institute for physical chemistry II, Heinrich-Heine-Universität Düsseldorf, Universitätsstr.1, 

40225 Düsseldorf, Germany 


Weiss, Heike info: 


Wenz, Tina info: University of Cologne, Institute for Genetics, Zülpicher Str. 47A, 50674 Köln, Germany 


during aging 

Wenzel, Dirk info: Max Planck Institute for Biophysical Chemistry, Goettingen, Germany 


elegans 

25




Werner, Alexandra info: 

M 3: Age-dependend kynurenylation of a specific tryptophan residue in the ATP synthase 

alpha subunit of Podospora anserina 

Werner, Andreas info: Newcastle University 

O 16: Gene regulation by natural antisense transcripts during sperm development and 

ageing: An example of antagonistic pleiotrophy? 

Werner, Christian info: Universitätsklinikum des Saarlandes, Innere Medizin III 



Wester-Rosenloef, Lena info: 


Wiesner, Rudolf info: 


Wild, Klemens info: 

A 2: Structure of the signaling domain of Alzheimer disease amyloid precursor protein in 

complex with Fe65-PTB2 

Willmes, Diana Maria info: 


RESISTANCE 

Wirth, Martina info: Max Planck Institute for Biophysical Chemistry, Goettingen, Germany/GGNB doctoral 

program “Molecular Biology” - International Max Planck Research School 


elegans 

Wirth, Thomas info: 



Wlaschek, M. info: 


Wlaschek, Meinhard info: Department of Dermatology and Allergic Diseases, University of Ulm, 89081 Ulm, Germany 


Wollam, Joshua info: 

Thu., 8 April, 15.00: Steroid hormone control of the reproductive longevity pathway 

Wollnik, Bernd info: Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany 



Wolters, Dirk info: 


Wunderlich, F. Thomas info: 






Xiang, Wei info: Institut für Biochemie, Friedrich-Alexander Universität Erlangen-Nürnberg 

A 9: Protein nitration and protein S-nitrosylation in retinal neurodegeneration 

Xu, Jian info: Research Associate 


Zheng, Yi info: Division of Experimental Hematology, Department of Pediatrics, Cincinnati Children’s 

Hospital Medical Center, Cincinnati, OH 



Zimmer, Julia info: 


Zollner, Gernot info: 



Zovoilis, Athanasios info: Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute Göttingen, 


O 30: AN ALTERED HIPPOCAMPAL HISTONE CODE IS ASSOCIATED WITH 

AGE- DEPENDENT MEMORY IMPAIRMENT 

26

Abstracts - Invited Speaker (in chronological order) 

_________________________________________________________ 

Thu., 8 April, 8.40 - DOI: 10.3288/contoo.paper.694 

Growth Hormone, Insuline and Aging 

Elucidation of the role of insulin/insulin-like growth factor signaling (IIS) 

in the control of aging in widely diverse organisms stands out as one of 

the most exciting developments in experimental gerontology in the last 

20 years. In mammals, IIS is difficult, if not impossible, to separate from 

growth hormone (GH) because IGF-1 mediates many GH actions and 

GH has important anti-insulinemic effects. Mutations leading to GH 

deficiency or resistance in laboratory mice produce a robust extension 

of longevity in both sexes along with numerous indications of delayed 

aging and longer “healthspan.” It remains to be demonstrated whether 

equally pronounced alterations in aging can be produced by altering IIS 

in mammals. 

The search for mechanisms responsible for effects of reduced GH 

signaling on aging produced results implicating involvement of 

alterations in stress resistance, target of rapamycin (TOR) axis, 

mitochondrial functions, genome maintenance, apoptosis, insulin 

sensitivity, adipokine levels, etc. echoing some of the findings in animals 

subjected to calorie restriction. Studies in Ghr-/- and Prop1df mice in 

our laboratory focus attention on enhanced insulin sensitivity combined 

with reduced insulin levels, and on reduced circulating IGF-1 co-existing 

with preservation of some of the local IGF-1 actions. 

In contrast to the remarkable extension of longevity in GH deficient and 

GH resistant mice, the relationship of GH to normal aging and the 

potential utility of modifying GH signaling in anti-aging and geriatric 

medicine are poorly understood and highly controversial. The inverse 

relationship of growth (as assessed by adult body size) and life 

expectancy clearly applies to species other than mice but existence of a 

similar relationship in the human continues to be debated. While 

reduced somatotropic signaling in women has been associated with 

reduced old age mortality and attainment of exceptional longevity, 

somatopause is often viewed as an important etiological factor in agerelated 

functional decline. In contrast to early claims, 

evidence for broad anti-aging effects of GH therapy is generally 

considered as less than convincing, but potential utility of GH and GHreleasers 

for the prevention and/or treatment of sarcopenia and frailty 

certainly merits careful evaluation. 

Supported by NIA, Ellison Medical Foundation and Glenn Foundation 

for Medical Research. 

Authors: Andrzej Bartke 

_________________________________________________________ 


Finding specificity in the genetics of aging 

Genetic studies in organisms ranging from yeast to mammals have 

revealed several independent pathways capable of regulating lifespan 

and youthfulness. In the nematode Caenorhabditis elegans, 

perturbations in at least three distinct processes -- insulin signaling, 

mitochondrial respiration, and caloric intake -- create long-lived, stressresistant, 

thermotolerant animals (Dillin et al., 2002b; Kenyon et al., 

1993; Lakowski and Hekimi, 1998; Lee et al., 2003b). Single gene 

mutations affecting these pathways not only significantly extend 

lifespan, but also impair larger signaling networks responsible for 

regulating multiple functions. Manipulations of these core pathway 

components result in a wide range of metabolic and physiological 

consequences. Because signaling cascades often appear to converge 

upon a single transcription factor, additional temporal, spatial, and 

physical modification of the pathway is necessary to ensure specificity. 

To fully understand the specific molecular mechanisms of aging, it is 

imperative to understand how each pathway differentially regulates its 

secondary processes. Recently, our lab discovered a highly conserved 

transcription factor (PHA-4) and co-regulator (SMK-1) required for 

Dietary Restriction (DR) (Panowski et al., 2007). Furthermore, we have 

extended the discovery of this pathway to now include an E2 and E3 

ubiquitin ligase complex. IN this presentation we will provide new 

information that reveals the core nodes in which the ligase complex and 

its downstream transcription factor complex regulates in response to 

nutrient limitation that results in increased longevity. 

Authors: William Mair, Nathan Baird, Siler Panowski, Andrea Corrano, 

Andrew Dillin 

27 

_________________________________________________________ 


Molecular mechanisms linking diet, disease, and aging. 

Aging is controlled by a complex interaction between environmental and 

genetic factors. The best-characterized environmental determinant of 

longevity is dietary restriction, defined as a reduction in nutrient 

availability in the absence of malnutrition. The Target of Rapamycin 

(TOR) kinase has emerged as a key mediator of longevity and 

healthspan in response to dietary restriction, and interventions that 

reduce TOR signaling are now known to slow aging in organisms from 

yeast to mice. More recently, we have found that the response to 

reduced oxygen availability, referred to as the hypoxic response, also 

promotes longevity and healthspan in C. elegans. The results of our 

studies to define the molecular mechanisms by which dietary restriction 

and the hypoxic response modulate aging will be discussed. 

Authors: Matt Kaeberlein 

_________________________________________________________ 


Multiple Approaches to Lifespan Extension in Mice 

Like blind men patting down various sections of a patient elephant, 

biogerontologists are gradually assembling a mental image of how 

aging works by seeking overlaps (and discrepancies) among a growing 

set of anti-aging interventions. This talk presents a potpourri of data 

from four such systems. (1) Diets low in methionine extended mouse 

lifespan even when initiated as late as 12 months of age. Biochemical 

signatures of caloric restriction (activation of hepatic ERK and p38, 

depression of TOR, multiple changes in mRNA levels) were not seen in 

these Meth-R mice, suggesting that the two dietary interventions work 

by non-identical pathways. (2) A mere 3 weeks of early-life food 

restriction, imposed by increasing the number of pups per litter from 

birth to weaning, was sufficient to lead to an 18% increase in median 

longevity, with a significant increase in survival to the 90th percentile 

age. These data suggest that mice may be especially sensitive to the 

effects of food restriction when they are very young. (3) Genetic ablation 

of a pro-inflammatory cytokine, MIF, led to a 16% increase in lifespan, 

but did not impair the ability of caloric restriction to extend lifespan still 

further. Because MIF is a secreted protein, drugs that block MIF action 

may deserve evaluation for anti-aging effects. (4) Three agents, NDGA, 

aspirin, and rapamycin, have been shown to produce significant 

extensions of lifespan in genetically heterogeneous mice. The 

rapamycin effect was the strongest, was seen in both males and 

females, and was seen in mice exposed to rapamycin either at 9 or at 

20 months of age. Other agents, including resveratrol at 400 and 1200 

ppm of diet, had no significant effects on longevity when tested in 

parallel with rapamycin. Evaluation of the biochemical pathways by 

which these manipulations extend lifespan may help to define the 

cellular and molecular factors that control rate of aging, and could 

potentially lead to the development of effective anti-aging medicines. 

Key collaborators: James Harper, David Harrison, Nancy Nadon, Amir 

Sadighi Akha, Randy Strong, Liou Sun. 

Authors: Richard Miller


_________________________________________________________ 


Long-Term Calorie Restriction in Humans 

Numerous studies on yeast, worms, flies, mice and rats have shown 

that calorie restriction (CR) slows aging and protects against cancer. 

There is relatively little known regarding the effects of calorie restriction 

in humans. To obtain information in humans on CR, we are studying 

members of the Calorie Restriction Society, who have been practicing 

severe CR (we estimate a 25 to 30% reduction in calories) for many 

years. These individuals are powerfully protected against 

atherosclerosis and type 2 diabetes as evidenced by low LDL 

cholesterol and triglyceride levels, high LDL cholesterol, plaque free 

arteries, and very low blood pressure. They also have some of the 

same adaptations as CR rodents, including very low levels of 

inflammation markers including hsCRP, IL6 and TNF α, 

and of a number 

of hormones, including triiodothyronine, testosterone and leptin. On the 

other hand, adiponectin and cortisol levels are high. One of the factors 

thought to slow aging in CR rodents is a low level of IGF-1, with 

reduced signaling via the PI-3K/Akt/mTOR enzymatic pathway. In 

contrast to rodents, CR per se does not lower IGF-1 in humans. A 

reduction in protein intake is also needed. Because of this finding, most 

of the CR Society members, who had a relatively high protein intake 

(1.73 ± 0.4 g/kg body weight), have reduced this protein intake. Longterm 

CR provides a number of major health benefits and is of 

considerable research interest. However, it has a number of unpleasant 

effects that make it impossible for the great majority of people to 

practice. 

Authors: John Holloszy 

_________________________________________________________ 


How much mtDNA mutations contribute to ageing: lessons from 

mtDNA mutator mice 

Although mitochondria have long been anticipated as a perpetrator of 

aging, there was little experimental evidence to link these changes 

directly with the cellular pathology of aging. MtDNA mutator mouse was 

the first model showing that collective amount of somatic mtDNA 

mutation could cause ageing in experimental animals. Before this 

mtDNA mutations and especially random mtDNA point mutations were 

seen more as a consequence than the driving force of ageing. The 

mtDNA mutator mice have high levels of point mutations and linear 

deletions of mtDNA causing a progressive respiratory chain dysfunction 

and a premature ageing phenotype. We have now performed molecular 

analyses to determine the mechanism whereby these mtDNA mutations 

impair respiratory chain function. We report that the steady-state levels 

of tRNAs and other mitochondrial transcripts are normal and that 

mitochondrial translation is unimpaired in mtDNA mutator mice. These 

findings refute recent claims that circular mtDNA molecules with large 

deletions are driving the premature ageing phenotype. We further show 

that the assembly of several respiratory chain complexes is severely 

impaired despite normal levels of protein subunits. These results 

strongly argue that the observed phenotypes in mtDNA mutator mice 

are a direct consequence of the accumulation of mtDNA point mutations 

in protein-coding genes, leading to a decreased assembly of the 

respiratory chain complexes, respiratory chain dysfunction and thus to 

premature ageing. 

Authors: Aleksandra Trifunovic 

28 

_________________________________________________________ 


Steroid hormone control of the reproductive longevity pathway 

In many species, decreased reproduction often correlates with 

increased longevity, but the molecular basis of this relationship is 

obscure. Elegant studies in C. elegans reveal that regulatory signaling 

from gonad to soma may underlie the relationship of extended survival 

and reproduction (1). At hatch, the gonadal primordium consists of two 

germline precursor cells (Z2, Z3), and two somatic gonadal precursors 

(Z1, Z4). When germline precursors are removed by laser microsurgery, 

animals become sterile adults that live 50% longer than mock-treated 

animals. Interestingly, when somatic gonadal precursors are further 

removed, animals have normal life spans. Thus the energetic costs of 

germline production cannot wholly account for increased longevity. 

Consistent with intercellular signaling, germline ablation triggers nuclear 

localization of DAF-16/FOXO in intestinal cells (2). FOXO translocation 

is visibly dependent on the steroid hormone receptor DAF-12 and its 

ligand, dafachronic acid (1,2,3). Moreover, germline longevity requires 

FOXO, as well as steroid hormone receptor signaling (1,3). Here we 

describe further components of the steroid hormone pathway, which 

influence reproductive longevity. These molecular events reveal that 

tissue communication and hormonal regulation underlie reproductive 

longevity, and that diversion of resources to the germline may not 

adequately describe why reproductively active animals are relatively 

shorter lived. 

1. Hsin, H. & Kenyon, C. (1999) Nature 399, 362-366. 

2. Berman, J. R. & Kenyon, C. (2006) Cell 124, 1055-1068. 

3. Gerisch, B., et al. (2007) PNAS 104, 5014-5019. 

Authors: Joshua Wollam, Birgit Gerisch, Adam Antebi 

_________________________________________________________ 

Thu., 8 April, 15.35 

Growth signaling pathways and aging: from yeast to humans 

no abstract submitted 

Author: Valter D. Longo 

_________________________________________________________ 

Thu., 8 April, 16.10 

BayerSchering Pharma Thesis Prize: A Prokaryotic Perspective on 

Pentameric Ligand-Gated Ion Channels 

The pentameric ligand gated ion channels (pLGIC) constitute a family of 

selective ion channels that are key players in the control of electric 

signaling at chemical synapses. The family codes for a structurally 

conserved scaffold of channel proteins that open in response to the 

binding of neurotransmitter molecules. We have determined the X-ray 

structures of two prokaryotic family members from the bacterium Erwinia 

chrysanthemi (ELIC) at 3.3 Å resolution [1] and from the bacterium 

Gloeobacter violaceus (GLIC) at 3.1Ǻ resolution [2]. Both proteins form 

cation selective channels and bear most of the structural hallmarks of the 

family including the N-terminal extracellular ligand binding domain and the 

four helices of the pore domain. Despite the overall similarity, both 

structures adopt distinct conformations of the ion conduction pathway: 

The structure of ELIC shows a nonconductive state with rings of 

hydrophobic residues at the extracellular side of the pore preventing ion 

permeation. This hydrophobic barrier has opened in the structure of GLIC 

to a funnel shaped pore, where a ring of glutamate residues at the 

intracellular constriction of the pore creates an ion coordination site. GLIC 

is thus believed to represent a conducting conformation of the channel. 

In combination, both structures suggest a novel gating mechanism for 

pentameric ligand-gated ion channels where channel opening proceeds 

by a change in the tilt of the pore-forming helices. Our study thus provides 

a first structural view at high resolution into how a pLGIC may open and 

selectively conduct ions. 

Authors: Ricarda Hilf


_________________________________________________________ 

Thu., 8 April, 19.00 

Feodor Lynen Lecture: From worms to mammals: genes that can 

increase lifespan 


Author: Cynthia Kenyon 

_________________________________________________________ 

Fri., 9 April, 09.00 

Regulation of mtDNA expression 


Author: Nils-Göran Larsson 

_________________________________________________________ 

Fri., 9 April, 09.35 - DOI: 10.3288/contoo.paper.695 

The bioenergetic and epigenomic interaction in health and disease 

Until now, the prevailing paradigms in Western medicine have been the 

anatomical paradigm of disease which posits that tissue-specific 

symptoms are due to tissue-specific structural defects and the 

Mendelian paradigm of genetics which posits that if a disease is 

inherited according to the Laws of Mendel it is genetic and if not it is 

environmental. The epigenome is invoked to explain the environmental 

modulation of the nuclear gene expression. However, life requires both 

structure and energy and the over 1500 mitochondrial energy genes are 

dispersed across the chromosomes plus the maternally inherited 

mitochondrial DNA. The cells and tissues most affected by aging are 

those most reliant on mitochondrial energy and the mitochondria lie at 

the interface between calories and physiology. The epigenome and the 

signal transduction pathways are regulated by protein phosphorylation 

by ATP, acetylation via acetyl-CoA, and methylation by Sadenosylmethionine, 

all driven by mitochondrial high energy substrates 

modulated by available calories. Furthermore, mitochondrial redox 

chemistry regulates reactive oxygen production and thiol/disulfide 

chemistry and these also regulate cellular signaling and function. 

Therefore, bioenergetics and mitochondrial genetics are the missing 

factors which have inhibited our capacity to address the biology and 

genetics of the age-related metabolic and degenerative diseases. 

Kokoszka JE, Coskun P, Esposito L, Wallace DC. 2001. Increased 

mitochondrial oxidative stress in the Sod2 (+/−) mouse results in the 

age-related decline of mitochondrial function culminating in increased 

apoptosis. Proc. Natl. Acad. Sci. USA 98:2278–83. 

Melov S, Hinerfeld D, Esposito L, Wallace DC. 1997. Multi-organ 

characterization of mitochondrial genomic rearrangements in ad libitum 

and caloric restricted mice show striking somatic mitochondrial DNA 

rearrangements with age. Nucleic Acids Res. 25:974–82. 

Melov S, Schneider JA, Coskun PE, Bennett DA, Wallace DC. 1999. 

Mitochondrial DNA rearrangements in aging human brain and in situ 

PCR of mtDNA. Neurobiol. Aging 20:565–71. 

Murdock DG, Christacos NC, Wallace DC. 2000. The age-related 

accumulation of a mitochondrial DNA control region mutation in muscle, 

but not brain, detected by a sensitive PNA-directed PCR clamping 

based method. Nucleic Acids Res. 28:4350–55. 

Wallace DC. 1999. Mitochondrial diseases in man and mouse. Science 

283:1482–88. 

Wallace DC, Brown MD, Lott MT. 1999. Mitochondrial DNA variation in 

human evolution and disease. Gene 238:211–30. 

Authors: Douglas C. Wallace 

29 

_________________________________________________________ 


Mitochondrial dysfunction, oxidative stress and age-related 

skeletal muscle atrophy 

The mitochondrial theory of aging predicts that aging is associated with an 

increase in mitochondrial oxidative stress and decreased mitochondrial 

function. Mitochondrial dysfunction in skeletal muscle has been implicated in 

the etiology of age-related muscle loss (sarcopenia). To study the role of 

chronic oxidative stress and mitochondrial dysfunction in vivo, we used a 

mouse model that lacks the antioxidant enzyme CuZnSOD (Sod1). Sod1-/mice 

are characterized by high levels of oxidative stress/damage and an 

acceleration of sarcopenia. Muscle atrophy in Sod1-/- mice is accompanied 

by a progressive decline in mitochondrial bioenergetic function and an 

elevation of mitochondrial generation of reactive oxygen species. 

Mitochondria isolated from muscle of Sod1-/- mice are also more sensitive to 

induction of mitochondrial-mediated apoptosis, resulting in greater release of 

pro-apoptotic proteins and loss of myonuclei in muscle fibers. Furthermore, 

aged Sod1-/- mice show a striking increase in mitochondrial content near the 

neuromuscular junctions (NMJs) that is associated with disruption of 

postsynaptic endplates and a significant loss of contractile force in muscle 

from Sod1-/- mice. Caloric restriction in Sod1-/- mice is associated with lower 

mitochondrial ROS generation, decreased oxidative damage and reduction 

in age-related loss of muscle mass. The age associated disruption in NMJs 

is also partially protected in Sod1-/- CR mice (63% of the neuromuscular 

junction (NMJ) are denervated in Sod1-/- but only 38% are denervated in 

Sod1-/- CR). Overall, these data suggest that mitochondrial function and 

dysregulation of oxidative stress can alter skeletal muscle mass though 

disruption of the neuromuscular junction. 

Authors: Youngmok Jang, Yuhong Liu, Holly Van Remmen 

_________________________________________________________ 

Fri., 9 April, 11.15 

SIRT1 controls neuro-endocrine signalling 


Author: Leonard P. Guarente 

_________________________________________________________ 


Unequal inheritance and retrograde transport of protein 

aggregates - a means to rejuvenation in yeast 

Asymmetry in unicellular systems might develop into aging and it has been 

suggested that damage segregation and sibling-specific deterioration may 

confer a selective advantage in such organisms1. In budding yeast, the 

paradigm sirtuin, Sir2p, is required for establishing cellular age asymmetry, 

which includes the retention of damaged and aggregated proteins in mother 

cells2, 3, 4. By establishing the global genetic interaction network of SIR2 we 

identified the polarisome as the machinery required for segregating protein 

aggregates recognized by the remodeling factor Hsp1045 . Apart from being 

essential in inhibiting transmission of damage into daughter cells, this 

machinery is demonstrated to allow the emerging daughter to translocate 

aggregates back into its progenitor. This may be the first documentation of a 

polarized flow of material from the daughter to the mother cell. The role of 

Sir2p in cytoskeletal functions and polarity is linked to the CCT chaperonin of 

sir2 cells being slower than wild type CCT in folding actin. The data will be 

discussed in relation to recent models hypothesizing that polarity may have 

evolved to avoid clonal senescence by establishing an aging (soma-like) and 

rejuvenated (germ-like) lineage. 

1. Erjavec N. Cvijovic M. Klipp E. and Nyström T. (2008) Selective benefits of 

damage partitioning in unicellular systems and its effects on aging. Proc. 

Natl. Acad. Sci. USA 

2. Aguilaniu, H., Gustafsson, L., Rigoulet, M., and Nyström, T. (2003) 

Asymmetric inheritance of oxidatively damaged proteins during cytokinesis. 

Science 299:1751-1753. 

3. Erjavek, N., Larsson, L., Grantham, J. and Nyström T. (2007) Accelerated 

aging and failure to segregate damaged proteins in SIR2 mutants can be 

suppressed by overproducing the protein aggregation-remodeling factor 

Hsp104p. Genes Develop. 21:2410-2421. 

4. Erjavek, N., and Nyström T. (2007) Sir2p-dependent cytoskeleton 

formation and mitotic segregation of damaged proteins – a process 

regulating the antioxidant capacity of yeast daughter cells. Proc. Natl. Acad. 

Sci. USA 26:10877-8. 

5. Liu, B. Larsson, K. Caballero, A. Hao, X. Öling, D. Grantham, J. and 

Nyström, T. (2009) The Polarisome is Required for segregation and 

Retrograde Transport of Protein Aggregates. Cell In print 

Authors: Thomas Nystrom


_________________________________________________________ 


Otto Warburg Lecture: How animal viruses enter their host cells 

Current work in our group focuses on the interactions that occur 

between animal viruses and their host cells. Using cellular, molecular, 

and systems biology approaches in combination with live cell imaging 

and electron microscopy, our goal is to elucidate how virus particles 

bind to cells, how they are internalized by endocytosis, and how they 

are delivered to various organelles such as endosomes and the 

endoplasmic reticulum. We also analyse the subsequent steps to find 

out how the viral genome and accessory proteins escape into the 

cytosol or the nucleus. 

A variety of perturbation techniques and high and medium through put 

siRNA screens have allowed identification of viral infectomes, i.e. the 

collection of cellular proteins and pathways involved in assisting entry of 

different viruses. Currently, the group is particularly interested in the 

signaling pathways that vaccinia virus use to trigger cell surface 

blebbing and macropinocytic internalization. To induce uptake, the 

mature particles (MVs) of vaccinia mimic apoptotic bodies. We are also 

following the lipid raft-dependent uptake pathway of simian virus 40 

(SV40), which uses a ganglioside, GM1, as its cell surface receptor to 

move from the plasma membrane via endosomes to the ER and the 

nucleus. The dynamics of lateral movement of the virus, as well as the 

deformation of the plasma membrane leading to the formation of a tigtfitting 

endocytic vesicle, can be analyzed by powerful, new light 

microscopy techniques. 

Authors: Ari Helenius 

_________________________________________________________ 


Potential Role of Adiponectin and Adiponectin Receptors in 

Metabolic Fitness and Logevity 

Adiponectin is an anti-diabetic adipokine, which facilitates glucose and 

lipid metabolism to increase insulin sensitivity. Decreased plasma 

adiponectin in obesity is causally involved in insulin resistance and 

metabolic syndrome. Adiponectin receptors, AdipoR1, AdipoR2, 

possess seven-transmembrane topology with the amino terminus 

located intracellularly, which is opposite to G-protein coupled receptors. 

In liver, activation of AdipoR1 by adiponectin stimulates AMP kinase 

(AMPK) pathway and that of AdipoR2 stimulates PPARa pathway, 

thereby decreasing gluconeogenesis and lipogenesis, increasing fatty 

acid oxidation, simultaneuosly causing suppression of inflammation and 

oxidative stress. In muscle, adiponectin stimulates AMPK activity via 

AdipoR1, thereby activating of Sirt1 and PGC1-a, leading to 

increased mitochondrial biogenesis and metabolic fitness. AdipoR1 in 

macrophage and AdipoR2 in endothelial cells are involved in 

suppression of inflammation–related neointimal hyperplasia . AdipoR1 

and AdipoR2 are down-regulated in obesity, which is also casually 

involved in insulin resistance linked to obesity. Thus, adiponectin and 

adiponectin receptors stimulates longevity genes such as AMPK and 

Sirt1 and adiponectin transgenic mice indeed showed increased 

lifespan. Adiponectin and adiponectin receptors are also crucially 

involved in insulin resistance, metabolic syndrome, diabetes, and 

vascular inflammation and thus may serve as molecular targets of 

treatment strategy of these diseases. 

1) Nature Medicine 7:941-946, 2001, 2) Nature Medicine 8: 1288-1295, 

2003, 3) Nature 423: 762-769, 2003, 4) J. Biol. Chem. 279: 30817- 

30822, 2004, 5) Endocrine Reviews 26: 439-451, 2005, 6 ) J.Biol.Chem. 

281: 8748-8755, 2006, 7) J.Clin.Invest. 116: 1784-1792, 2006, 8) 

Nature Medicine 13: 332-339, 2007, 9) Cell Metabolism 6:55-68, 2007, 

10) FEBS Letters, 582: 74-80, 2008 

Authors: Takashi Kadowaki 

30 

_________________________________________________________ 


The aging auditory system 

The most common manifestation of age-induced hearing loss, 

presbycusis, is the loss of sensitivity for high frequency sounds resulting 

in difficulties in speech perception, hearing in noisy backgrounds, and 

distorted loudness perception. These abnormalities typically involve 

progressive damage to the inner ear and spiral ganglion neurons 

leading to a diminished input into the central auditory nervous system. 

The central components of the auditory system can also undergo direct 

morphological and physiological changes induced by the biological 

effects of aging. A combination of direct and secondary changes is most 

likely to contribute to the manifestations of the aging auditory system. 

This presentation will describe the molecular and physiological changes 

that occur during aging in experimental animals and human subjects. 

Authors: Barbara Canlon, 

Konstantina Charitidi, Xianzhi Niu, Inna 

Meltser, Peter Johansson, Dan Hasson 

_________________________________________________________ 

Fri., 9 April, 17.10 

From a little mutant mouse to human medicine for bone loss 


Author: Josef M. Penninger 

_________________________________________________________ 

Sat., 10 April, 9.00 

Clues to the causes of Alzheimer's Disease from genetics 


Author: Rudolph Tanzi 

_________________________________________________________ 

Sat., 10 April, 9.35 - DOI: 10.3288/contoo.paper.681 

Molecular insights into mitochondrial dysfunction and 

neurodegeneration in Parkinson's Disease 

Parkinson's disease (PD) is a prevalent neurodegenerative disorder. It 

is characterized by bradykinesia, rigidity, rest tremor and postural 

instability. In addition, patients experience cognitive dysfunction and 

neuropsychiatric problems including anxiety and depression. Many 

patients also develop autonomic dysfunction. Pathologically PD is 

characterized by the progressive degeneration of dopamine (DA) 

neurons and the accumulation and aggregation of alpha-synuclein, 

which is the major structural component of Lewy bodies and neurites. 

Besides degeneration of DA neurons, other neuronal populations 

degenerate as well, which account for the non-motor manifestations of 

PD. The cause of PD remains poorly characterized, but the discovery of 

both autosomal dominant and recessive genes that are mutated in 

familial PD has provided tremendous new insight into the pathogenesis 

of PD. Mutations in alpha-synuclein and LRRK2 cause autosomal 

dominant PD and mutations in parkin, PINK-1 and DJ-1 cause 

autosomal recessive PD. Mutations in these genes cause PD through 

complex and perhaps related mechanisms. Although the discovery and 

characterization of these genes has led to tremendous new insights into 

the pathogenesis of hereditary PD, the majority of PD is sporadic. 

Consistent observations in sporadic PD indicates that mitochondrial 

dysfunction and oxidative stress play prominent roles in the 

pathogenesis of PD. The underlying basis for mitochondrial dysfunction 

is not known. Understanding the molecular mechanisms of hereditary 

forms of PD is leading to new insights into the mechanisms of 

mitochondrial dysfunction in sporadic PD. These new insights are 

leading to innovative targets for the treatment of this disorder. 

Authors: Ted M. Dawson


_________________________________________________________ 

Sat., 10 April, 10.10 

Quality control of DNA and the connection with aging 


Author: Jan. H.J. Hoeijmakers 

_________________________________________________________ 

Sat., 10 April, 11.15 

DNA damage links inflammation, cancer and aging 


Author: Judith Campisi 

_________________________________________________________ 


Telomere Dysfunction, DNA Damage, and Stem Cell Aging 

Telomeres shorten in almost all human tissues during aging. In addition, 

accelerated telomere shortening occurs in organs affected by chronic 

disease, for example in liver in response to chronic hepatitis. There is 

an association with an increasing expression of biomarkers of telomere 

dysfunction and DNA damage with the evolution of age-associated 

disease. I will summarize recent work from our laboratory indicating that 

telomerase mutations associated with progressive organ failure in 

patients with chronic liver disease and that lifestyle factors influence on 

the accumulation of DNA damage and telomere dysfunction during 

aging. 

There is emerging evidence that the functional capacity of stem cells 

declines during organismal aging. In previous studies we have shown 

that telomere dysfunction induces cell intrinsic checkpoint and 

environmental alteration that limit the function of adult tissue stem cells. 

During the meeting I will present current work from our laboratory 

showing that alterations in the systemic environment are the main 

cause of impaired B- and T-lymphopoiesis in aging mice with 

dysfunctional telomeres. Moreover, I will present data indicating that 

p53 exerts a tissue-protective function in telomere driven aging by 

depleting chromosomal instable stem cells. 

Authors: K. Lenhard Rudolph 

31 

_________________________________________________________ 


Aging of hematopoietic stem cells: a program or noise? 

Hematopoietic stem cells are capable to sustain the production of 

multiple distinct blood cells throughout the lifetime of an organism. At 

the same time, their self-renewal potential allows maintenance of stem 

cell numbers.. Yet, numerous studies have indicated that changes in 

both stem cell pool size and functional activity are evident during normal 

aging. Our previous studies have indicated that these age-dependent 

phenotypes are mouse-strain dependent, and suggest the presence of 

a genetic component to stem cell aging. 

Efforts to identify a “HSC aging signature” by comparing gene 

expression profiles of HSCs purified from pooled groups of young and 

old mice have resulted in surprisingly little overlap. While this may be in 

part due to technical variables, it is also possible that a unique aged 

stem cell profile does not exist. Rather, age-related changes may arise 

as a result of stochastic changes, in combination with cellular 

(darwinian) selection of stem cell clones over time. One approach to 

resolve this issue is to determine whether HSC aging occurs similarly 

from mouse to mouse, and from strain to strain. Therefore, we 

measured a variety of physiological and HSC-specific parameters in 20 

individual young and 40 individual old C57Bl/6 or DBA/2 mice. “LT- 

HSCs” (defined as CD34-Lin-Sca+cKit+ CD48- CD150+EPCR+) and 

“progenitors” (defined as CD34+Lin-Sca+cKit+CD48+CD150-) were 

purified from each mouse As expected, there was little variation in the 

frequency of phenotypically defined LT-HSCs in young mice. In contrast, 

marked variation was observed in individual old mice, ranging from no 

change to a 20-fold increase. To measure functional frequency, we 

performed multiple in vitro and in vivo stem cell assays. “Progenitors” 

purified from old or young mice had a similar functional frequency, while 

“LT-HSCs” from old mice had a consistently lower functional frequency 

than “LT-HSCs” from young mice. Combining the phenotypic and 

functional measurements from each mouse revealed that the frequency 

of functionally defined HSCs increased with age an average of 3-fold. 

However, this coincided with an extensive mouse-to-mouse variability, 

ranging from a 2-fold decrease to a 10-fold increase. Global gene 

expression analysis was performed on LT-HSCs and progenitors from 

the individual C57Bl/6 mice, and analysis of this data is ongoing. We 

expect this to reveal genes that correlate with the functional parameters 

tested. Most importantly, our data should allow to determine whether a 

specific stem cell-aging signature actually exist, or whether 

transcriptional infidelity (generating random noise), is a hallmark of stem 

cell aging and could contribute to demise of stem cell function. 

Authors: Brad Dykstra, Sandra Olthof, Martha Ritsema, Jaring 

Schreuder, Alice Gerrits, Leonid Bystrykh, Gerald de Haan

Poster Abstracts - A - Aging-Associated Diseases 

_________________________________________________________ 

A1- 

DOI: 10.3288/contoo.paper.667 

Chaperone-assisted selective autophagy is essential for muscle 

proteostasis 

The impairment of proteostasis significantly contributes to aging at the 

cellular level. Here we identify a chaperone-assisted degradation 

pathway that is important for proteostasis in muscles. The pathway 

mediates the continuous disposal of actin-anchoring proteins that are 

damaged during contraction through selective autophagy. Impairment of 

this process leads to a disintegration of actin-anchoring Z-disks and 

causes a progressively developing muscle weakness in flies, mice and 

men. Our data identify muscles as tissues that are highly sensitive to 

proteostasis alterations and shed light on the molecular mechanisms 

underlying diverse myopathies and age-dependent muscle weakness. 

Authors: Nikolaus Dick, Riga Tawo, Michael Dreiseidler, Verena Arndt, 

Jörg Höhfeld 

_________________________________________________________ 

A2- 


Structure of the signaling domain of Alzheimer disease amyloid 

precursor protein in complex with Fe65-PTB2 

Amyloidogenic processing of the amyloid precursor protein (APP) is a 

key event in Alzheimer disease pathogenesis. It creates the amyloid- β 

peptide (A β) 

which aggregates and forms the disease characteristic 

plaques and liberates the C-terminal APP intracellular domain (AICD) 

into the cytosol. Physiologically, the APP C-terminus is involved in APP 

internalization, transport and signal transduction by interacting with a 

variety of adaptor and signaling proteins. The interaction with the brainenriched 

adaptor protein Fe65 is important for many of these 

processes. However, it plays as well a significant role for pathogenic 

APP processing and Ab generation. 

Here we present the crystal structure of the AICD of human APP695 in 

complex with the C-terminal phosphotyrosine binding domain of Fe65 

(Fe65-PTB2)(1). In contrast to classical PTB domain/peptide 

interactions centering on the NPX(p)Y consensus motif of the peptide, 

the AICD/Fe65-PTB2 complex involves two surrounding α-helices 

resulting in a three times enlarged and unique interface. The N-terminal 

helix of the AICD is capped by threonine 668, which upon 

phosphorylation regulates complex dissociation and its increased 

phosphorylation is an important pathologic trait of Alzheimer disease. 

The structure of the AICD/Fe65-PTB2 complex gives a detailed view on 

a central protein complex involved in APP physiology and Alzheimer 

disease pathology. A large number of cell biological, molecular 

biological, and biochemical data can now be integrated in a solid 

mechanistic model for complex regulation by the Alzheimer disease 

relevant phosphorylation of threonine 668 within the AICD. 

(1) Radzimanowski J, Simon B, Sattler M, Beyreuther K, Sinning I and 

Wild K (2008) Embo Rep 9, 1134-1140. 

Authors: Jens Radzimanowski, Bernd Simon, Michael Sattler, Konrad 

Beyreuther, Irmgard Sinning, Klemens Wild 

32 

_________________________________________________________ 

A3- 


Identification of APP/FE65/TIP60-complex dependent pathways by 

using a comprehensive proteomic approach 

The short cytoplasmatic tail of the amyloid precursor protein (APP) is 

known as the APP intracellular domain (AICD) and its role in 

Alzheimer`s disease (AD) is yet poorly understood. AICD is belived to 

participate in transcriptional processes by forming an active complex 

with the multidomain adaptor protein FE65 and the histone 

acetyltransferase TIP60. This complex is referred to as the AFTcomplex 

(AICD/FE65/TIP60-complex) and might play an essential role 

in the pathogenesis of AD. Moreover, the role of the APP/FE65 family 

members (APLP1, APLP2, FE65L1, FE65L2) is yet unknown in the 

generation of the AFT-complex. Within our work we established a 

method in order to knockdown the components of the AFT-complex 

using a shRNA (short hairpin RNA) vector-based approach. In parallel, 

we used shRNA vectors for gene silencing of the family members of 

APP and FE65. Using those constructs we were able to induce an 

significant and efficient knockdown of the AFT-complex in human cell 

culture. Basing on these initial results we analyzed the AFT-complexdependent 

differentially expressed proteins using a comprehensive 

proteomic approach with state-of-the-art 2D-DIGE (Two Dimensional 

Difference In Gel Electrophoresis). Putatively AFT-dependent regulated 

target proteins were identified by mass spectrometric techniques and 

validated by a targeted MS based method (MRM, Multiple Reaction 

Monitoring). 

[1] Müller, T., Meyer, H. E., Egensperger, R., and Marcus, K. (2008) The 

amyloid precursor protein intracellular domain (AICD) as modulator of 

gene expression, apoptosis, and cytoskeletal dynamics-Relevance for 

Alzheimer's disease. Prog. Neurobiol. 85, 393-406. 

[2] Müller, T., Concannon, C. G., Ward, M. W., Walsh, C. M., Tirniceriu, 

A. L., Tribl, F., Kogel, D., Prehn, J. H., and Egensperger, R. (2007) 

Modulation of Gene Expression and Cytoskeletal Dynamics by the 

Amyloid Precursor Protein Intracellular Domain (AICD). Mol. Biol. Cell 

18, 201-210. 

[3] Müller, T., Jung, K., Ullrich, A., Schrötter, A., Meyer, H. E., Stephan, 

C., Egensperger, R., and Marcus, K. (2008) Disease state, age, sex, 

and post-mortem time-dependent expression of proteins in AD vs. 

control frontal cortex brain samples. Curr. Alzheimer Res. 5, 562-571. 

[4] Müller, T., Schrötter, A., Marcus, K. (2009) AICD – Wegbereiter des 

Morbus Alzheimer? Biospektrum 04.09, 374-376. 

Authors: Andreas Schrötter, Cornelia Schumbrutzki, Anke Schnabel, 

Christina Looße, Heike Piechura, Katja Kuhlmann, Bettina Warscheid, 

Helmut E. Meyer, Thorsten Müller, Katrin Marcus 

_________________________________________________________ 

A4- 


Oxidative Signaling in Aged T Lymphocytes 

Multicellular organisms undergo diverse qualitative changes during their 

life time. These changes are associated with a progressive decline in 

biological functions, an increased frequency of infections, autoimmunity, 

and cancer leading to increased mortality and morbidity. Recently, we 

have shown that in T lymphocytes a simultaneous calcium (Ca2+) influx 

into the cytosol together with the production of ROS (i.e. H2O2) is 

needed for induction of apoptosis in activated T lymphocytes (Activation 

Induced Cell Death/AICD). As AICD is important for the termination of 

an immune response and the maintenance of T cell homeostasis we 

were interested in ROS-related signaling pathways that may be 

changed in aged T cells. By means of whole genome gene expression 

analysis we identified several proteins that are involved in activationinduced 

signaling. We could show that one particular protein, named 

here aging factor 1 (AF-1), which is a critical negative regulator of the 

antioxidative defense system in the cell was dramatically upregulated in 

primary T cells from aged (>55 years) donors compared to T cells that 

were isolated from young donors (20-25 years).We assume that 

alterations in ROS generation and therefore destabilization of the redox 

equilibrium contribute to age-related immune dysfunction and 

inflammatory processes. Thus we suggest that AF-1 plays a decisive 

role in the aging immune system by deregulating ROS-induced gene 

expression. 

Authors: Sabine Sass, Peter H. Krammer, Karsten Gülow


_________________________________________________________ 

A5- 


Inflammatory and Age-related Pathologies in Mice with Ectopic 

Expression of Human PARP-1 

Poly(ADP-ribose) polymerase-1 (PARP-1) is a molecular sensor for 

DNA strand breaks and some unusual DNA structures and catalyzes 

poly(ADP-ribosyl)ation of nuclear proteins with NAD+ serving as 

substrate. PARP-1 is involved in the regulation of genomic integrity, 

transcription, inflammation, and cell death. Due to its versatile role, 

PARP-1 is discussed both as a longevity factor and an aging-promoting 

factor [1]. Recently, we generated a novel mouse model with ectopic 

expression of human PARP-1 (hPARP-1) [2]. Here we show that 

hPARP-1 mice exhibit impaired survival, accompanied by signs of 

premature aging such as sporadic kyphosis and reduced hair growth. 

Moreover, aging hPARP-1 mice show a shift in their tumor spectrum 

with increased incidences of carcinomas, in particular metastatic 

hepatocellular carcinomas. Some of the mutant mice developed several 

inflammation and age-associated pathologies prematurely, such as 

adiposity, nephropathy, dermatitis, crystal pneumonitis, hepatitis, 

hypertrophy of the islets of Langerhans and normocytic normochromic 

anemia. Furthermore, gene expression of proinflammatory cytokines 

TNF- α, 

IL-1, and IL-6 was dysregulated, suggesting that the above 

phenotype could be due to a continuous, low-level increase in proinflammatory 

stimuli, which would be consistent with the 'inflammaging' 

paradigm proposed in the literature [Mangerich et al., in Revision]. 

[1] Beneke and Bürkle, Nucleic Acids Res 2007;35(22):7456-65 

[2] Mangerich et al., Transgenic Res., 2009;18(2):261-79 

Authors: Aswin Mangerich, Benjamin Hanf, Oliver Popp, Arthur 

Fischbach, Alexander Bürkle 

_________________________________________________________ 

A6- 


HSF1-controlled and age-associated chaperone capacity in 

neurons and muscle cells of C. elegans 

Protein stability under changing conditions is of vital importance for the 

cell and under the control of a fine-tuned network of molecular 

chaperones. Aging and age-related neurodegenerative diseases are 

directly associated with enhanced protein instability. Employing C. 

elegans expressing GFP-tagged luciferase as a reporter for evaluation 

of protein stability we show that the chaperoning strategy of body wall 

muscle cells and neurons is significantly different and that both are 

differently affected by aging. Muscle cells of young worms are largely 

resistant to heat stress, which is directly mediated by the stress 

response controlled through Heat Shock Transcription Factor 1. During 

recovery following heat stress the ability to refold misfolded proteins is 

missing. Young neurons are highly susceptible to chronic heat stress, 

but show a high potency to refold or disaggregate proteins during 

subsequent recovery. The particular proteome instability in neurons 

results from a delayed induction of the heat shock response. In aged 

neurons protein stability is increased during heat stress, whereas 

muscle cells show enhanced protein instability due to a deteriorated 

heat shock response. An efficient refolding activity is absent in both 

aged tissues. These results provide molecular insights into the 

differential protein stabilization capacity in different tissues and during 

aging. In future studies, the influence of aging on the tissue-specific 

capacity of the chaperone network will be analyzed in more detail, 

employing dietary restriction as well as long- and short-lived C. elegans 

strains. 

Authors: Andreas Kern, Bianca Ackermann, Albrecht M. Clement, Heike 

Duerk, Christian Behl 

33 

_________________________________________________________ 

A7- 


Role of Longevity Assurance (Lass) Genes in Membrane 

Senescence: Tissue-specific changes of ceramide species 

composition in aged mice 

Cell membranes are complex and dynamic systems consisting of numerous 

types of lipids and integral membrane proteins. Many membrane-associated 

cellular processes such as cell surface receptor signaling or the uptake of 

pathogens occur at ceramide-enriched membrane platforms and are 

regulated by the abundance of ceramide and higher sphingolipids within 

these membrane domains. Since alterations in ceramide production seem to 

follow a development-aging continuum, we hypothesize that the impairment 

of membrane functionality in the elderly is due to age-related changes of the 

sphingolipid composition of membranes. 

The last step of the ceramide biosynthesis is catalyzed by enzymes 

belonging to the Lass (Longevity assurance) protein family, which includes 

six mammalian members (Lass 1-Lass 6). Strikingly, the first protein of the 

Lass family was identified in a screen for longevity-regulating genes in yeast. 

The Lass family members are expressed in a tissue-specific manner and 

show preferences for fatty acyl-CoAs of distinct chain lengths. Thus, the 

regulation of Lass genes represents an important mode of regulating 

membrane physiology through controlling the fatty acid composition of 

ceramides and ceramide-derived sphingolipids. 

In order to obtain insights into general changes of sphingolipid expression 

over age, we analyzed the ceramide species composition in different tissues 

of aged mice using a LC-MS/MS method which allows the simultaneous 

quantification of ceramide, glucosylceramide, and sphingomyelin species. 

Compared to six weeks old mice, aged mice showed tissue-specific 

alterations of ceramides species composition indicating differential 

expression of Lass 1-6 proteins, which may impact on the functionality of 

aged membranes. 

Authors: Susanne Brodesser, Carola Pongratz, Jens Brüning, Martin 

Krönke 

_________________________________________________________ 

A8- 


BROWN ADIPOSE TISSUE IS A MAJOR DETERMINANT OF 

PLASMA CLEARANCE AND ORGAN UPTAKE OF TRIGLYCERIDE- 

RICH LIPOPROTEINS 

Objective 

Elevated serum triglycerides represent an independent risk factor for 

developing cardiovascular disease. Chylomicrons and VLDL as 

triglyceride-rich lipoproteins (TRL) transport triglycerides to peripheral 

tissue for storage and energy supply. Recently it has been shown that 

adults have substantial amounts of functional brown adipose tissue 

(BAT). Murine as well as human BAT has a high energy demand 

especially when it is activated upon cold exposure. Here we investigate 

the role of TRL metabolism for energy supply of BAT upon cold 

exposure in mice. 

Methods 

C57BL/6J mice were kept for 24 hours in a cold room (10°C) or at room 

temperature. Plasma clearance and organ uptake of radiolabelled TRL 

were determined in control and cold-adapted mice in fasting and fed 

condition. 

Results 

After an oral fat gavage the postprandial serum triglyceride peak is 

diminished in cold-exposed mice. Accordingly we observe a massive 

acceleration of TRL turnover and a concomitant 20-fold increase in 

organ uptake of TRL components into BAT of cold-exposed mice. Taken 

together, we observe an accelerated TRL plasma clearance with an 

enormous shift in TRL uptake from liver to BAT in cold-exposed mice. 

Conclusion 

BAT is a novel determinant of plasma clearance and organ uptake of 

TRL especially upon cold exposure. Therefore, BAT activation by coldexposure 

or other means may be an interesting target in diseases 

associated with elevated serum triglycerides and elevated risk for 

cardiovascular diseases. 

Authors: Alexander Bartelt, Oliver T. Bruns, Martin Merkel, Joerg Heeren


_________________________________________________________ 

A9- 


Protein nitration and protein S-nitrosylation in retina 

neurodegeneration 

Nitric oxide (NO), a signaling molecule, controls a wide range of 

biological processes. NO and NO-related reactive nitrogen species 

have long been associated with neurodegenerative disorders and some 

aging-related diseases. One consequence of excessive nitrosative 

stress is the induction of tyrosine nitration in proteins. In addition, NO 

regulates the modification of critical cysteine residues in proteins. Both 

nitration and S-nitrosylation are posttranslational modifications (PTMs) 

of protein and can cause changes in protein structure, activity, 

interaction and subcellular localization. In this work, we studied the 

nitration and S-nitrosylation of retinal proteins exposed to oxidative 

stress or from a mouse model of retinal neurodegeneration (DBA/2J). 

Retinal proteins which were exposed to nitrosative stress or derived 

from DBA/2J mice showed increased nitration level, indicating a general 

induction of nitration both in the cell-free system and mouse model of 

oxidative stress. The regulation of S-nitrosylation is more complex. 

Incubation of retinal protein lysate with excess of NO donor induced 

increased S-nitrosylation. However, retinal proteins isolated from 

DBA/2J mice showed a significant decrease of nitrosylation. In 

particular, we observed the depletion of S-nitrosylation of GAPDH in the 

retina of DBA/2J mice. Our results suggest that S-nitrosothiol 

homeostasis is disrupted in retinal neurodegeneration. 

Authors: Wei Xiang, Cord-Michael Becker 

_________________________________________________________ 

A10- 


Phenothiazines influence the dopaminergic cell death in 

Caenorhabditis elegans models of Parkinson's disease 

Oxidative stress plays an important role in the pathogenesis of various 

neurodegenerative disorders. However, conventional antioxidant 

strategies have yet been of limited success. We have employed 

transgenic Caenorhabditis elegans expressing DsRed2 in dopaminergic 

neurons and CFP pan-neuronally, to characterize in larval and adult 

animals the effects of rotenone and 1-methyl-4-phenyl-pyridinium 

(MPP+) on the dopaminergic system. Investigating the antioxidant 

phenothiazine and different non-antioxidant phenothiazine derivatives, it 

was found that free phenothiazine exerted strong neuroprotection on 

the cellular level and resulted in a better performance in behavioral 

assays, whereas its non-antioxidant analogs did not show any 

protection. Other antioxidant tricyclic imines were likewise 

neuroprotective at their unusually low 500 nM concentration against 

dopaminergic neurodegeneration. 

Thus, rotenone and MPP+ seem to induce a largely prooxidative toxicity 

in C. elegans, which can be forestalled by nanomolar concentrations of 

certain chain-breaking antioxidants. 

Authors: Justyna B. Mocko, Andreas Kern, Bernd Moosmann, Christian 

Behl, Parvana Hajieva 

34 

_________________________________________________________ 

A11- 


Characterization of PML Nuclear Bodies in Human Adipocytes 

Objective 

Adipocytes are regulators of energy balance by storing dietary calories 

as lipids. Understanding adipocyte biology is therefore crucial for 

treatment of metabolic diseases such as type 2 diabetes. Promyelocytic 

Leukemia Nuclear Bodies (PML-NB), which appear as punctuate 

structures in the nucleus, have been implicated in cellular senescence 

and stress responses. Here we characterize PML-NB in a human 

adipocyte cell line. 

Methods 

Human adipocytes were differentiated from mesenchymal stem cells. 

PML-NB and components were visualized with immunofluorescence 

studies. The function of PML and PML-NB components such as DAXX 

and SP100 have been disrupted using lenti-viral gene delivery of 

shRNA. Adipocyte differentiation was monitored by quantitative realtime 

PCR measurement of adipocyte marker expression and lipid 

accumulation was quantified by Oil-Red-O staining. The inflammatory 

response to TNF� was analysed with quantitative real-time PCR and 

ELISA methods. 

Results 

During the transition from mesenchymal progenitor cells to adipocytes 

the shape and number of PML-NB decrease. Disruption of PML-NB 

does neither influence the expression of adipocyte markers nor lipid 

accumulation but modulates the inflammatory response. Here, the� 

proinflammatory interleukin 6 and the antiinflammatory adiponectin were 

inversely affected in the knockdown cell lines. 

Conclusion 

PML-NB are present in adipocytes and progenitor cells. PML-NB and 

components are not involved in differentiation cascades but are 

important as nuclear platforms for inflammatory processes. 

Authors: Leah Eissing, Alexander Bartelt, Hüseyin Sirma, Jörg Heeren 

_________________________________________________________ 

A12- 


Protein homeostasis in intrinsic versus nanoparticle- induced 

senescence 

The process of intrinsic senescence was first described by Hayflick and 

Moorhead. They observed that normal human fibroblasts enter a state 

of irreversible growth arrest after serial cultivation in vitro [1]. Here, we 

describe a nanoparticle (NP)-based method to induce a senescencelike 

phenotype in human epithelial cells that is characterized by an 

irreversible decrease of replication, transcription and cell proliferation, 

whereas cell viability remains unchanged. Notably, these alterations of 

cellular function are accompanied by induction of sodium dodecyl 

sulphate-resistant nuclear inclusions (NIs) of endogenous nuclear 

proteins, which exactly recapitulate NIs observed in inherited 

neurodegenerative disorders concerning their protein composition and 

biochemical properties [2]. NP-mediated formation of NIs is 

accompanied by a sustainable induction of the nuclear ubiquitin 

proteasome system (nUPS), e.g. proteasomal activity. Our aim is to 

compare NP-induced with intrinsic senescence by monitoring human 

fibroblasts during cumulative population doublings. Major emphasis is 

laid on the analysis of proteasomes, proteasomal proteolysis, and 

protein aggregation [3] in aging nuclei, and their correlation with 

senescence processes such as heterochromatin formation and p53 or 

p16/pRB signalling pathways. 

[1] Hayflick, L., and Moorhead, P.S. (1961). The serial cultivation of 

human diploid cell strains. Exp. Cell Res. 25, 585- 621. 

[2] Chen, M., Singer, L., Scharf, A. and von Mikecz, (2008). Nuclear 

polyglutamine-containing protein aggregates as active proteolytic 

centers. J Cell Biol. 180, 697-704. 

[3] von Mikecz, A., Chen, M., Rockel, T., Scharf, A. (2008). Localization 

of the nuclear ubiquitin proteasome system (nUPS), protein aggregation 

and proteasomal proteolysis in the cell nucleus. Methods Mol. Biol. 463, 

191-202. 

Authors: Anja Lena Singer, Min Chen, Anna von Mikecz


_________________________________________________________ 

A13- 


Thyroid hormone induces cellular senescence in neuroblastoma 

cells 

Cellular senescence is a genetic programme, with which higher eukaryotic 

cells undergo growth arrest in the G1 phase and pass irreversible into the 

G0 phase, but remain metabolically active. The induction of cellular 

senescence in tumor cells is a potential interesting mechanism that can be 

used for the inhibition of the tumor growth. 

The thyroid hormone receptor β (TR β) 

is known as a potent tumor 

suppressor. We show that thyroid hormone (T3) in neuroblastoma Neuro-2A 

cells expressing TRβ leads to growth arrest. Interestingly, T3 treatment of 

these cells leads to cellular senescence explaining the observed growth 

arrest. T3-treated cells exhibited the typical morphological changes of 

cellular senescence, a flattened and outspread cell shape with an enlarged 

nucleus. The expression of different specific cellular senescence markers 

like senescence- associated β-glactosidase (SA-β-Gal) and senescence 

associated heterochromatic foci (SAHF) were detected. 

On molecular level, treatment with T3 leads to a strong repression of c-myc 

mRNA level. This cellular oncogene is overexpressed in most neuroblastoma 

cells and is suggested as a key factor for tumor growth. Moreover, T3 

treatment causes an increase of the cell cycle inhibitor p21 mRNA and an 

induction of the corepressor Alien, which is known to interact with TR β. 

These results provide first underlying mechanism for TRβ-induced cellular 

senescence. 

Thus hormone-activated TRβ induces cellular senescence in neuroblastoma 

cells associated with repression of c-myc and upregulation of the tumor 

suppressor p21 and the corepressor Alien. 

Campisi J, Fagagna FA (2007) Cellular Senescence: when bad things 

happen to good cells. Molecular Cell Biology 8: 729-740. 

Wu CH, van Riggelen J, Yetil A, Fan AC, Bachireddy P, and Felsher DW 

(2007) Cellular Senescence is an important mechanism of tumor regression 

upon c-Myc inactivation. PNAS 104(32):13028-13033 

Authors: Claudia Gerlach, Viola Lorenz, Wiebke Hessenkemper, Sergiy 

Kyrylenko, Aria Baniahmad 

_________________________________________________________ 

A14- 


Histone deacetylase inhibitors class I, II or III induce cellular 

senescence in neuroblastoma and prostate cancer 

Cellular senescence leads to an irreversible block of cellular division 

capacity both in cell culture and in vivo. The induction of an irreversible cell 

cycle arrest is very useful for treatment of cancer. Histone deacetylases 

(HDACs) are considered as therapeutic targets to treat cancer patients. They 

inhibit cancer growth and are used in various clinical trials. Here, we 

analyzed whether specific inhibitors of HDACs induce cellular senescence in 

neuroblastoma and two different human prostate cancer cell lines, an 

androgen-dependent and an androgen-independent. Cellular senescence 

was detected by analysis of senescence markers such as the SA-β- galactosidase, the Senescence Associated Heterochromatin Foci (SAHFs) 

and western blot analysis of key cell cycle factors. Furthermore, we 

investigated the levels of Reactive Oxygen Species (ROS), known to induce 

a senescent-like cell cycle arrest. 

We found that HDAC inhibitors class I, II or III induce cellular senescence in 

neuroblastoma and in both used human prostate cancer cell lines. We also 

show that the cell cycle arrest is irreversible. Furthermore, HDAC class I and 

II inhibitors down-regulate the E2F1 protein levels in neuroblastoma cells. 

Whereas, the cell cycle inhibitor p21 protein levels seemed to be unchanged. 

Interestingly, ROS levels are increased after treatment with HDAC inhibitors 

class I, II or III. These results indicate an epigenetic regulation and an 

association of HDAC inhibition and ROS production with cellular 

senescence. The data underline that tumor cells can undergo cellular 

senescence and irreversible cell cycle arrest, which may further arise as a 

potent possibility for tumor suppression. 

K. Itahana, J. Campisi, G.P. Dimri "Methods to detect biomarkers of cellular 

senescence: the senescence-associated beta-galactosidase assay" 

Methods Mol Biol; 2007;371:21-31. 

I. Ben-Porath, R.A. Weinberg: "The signals and pathways activating cellular 

senescence" TheInternational Journal of Biochemistry and Cell Biology; 

2005;37:961-976. 

Authors: Julia Rödiger, Viola Lorenz, Wiebke Hessenkemper, Sergiy 

Kyrylenko, Aria Baniahmad 

35 

_________________________________________________________ 

A15- 


Decline of cellular calcium efflux in in vitro models of Parkinson's 

disease 

Parkinson's disease (PD) is a neurodegenerative disease associated 

with age. Alterations of calcium homeostasis are believed to play an 

important role in the pathogenesis of this disease. However, the 

molecular origin of these disturbances remains largely unknown. 

Employing an MPP+-based in vitro model of PD, we have investigated 

the cellular calcium-efflux systems: plasma membrane Ca2+-ATPase 

(PMCA), sarcoplasmatic reticulum Ca2+-ATPase (SERCA), and Na+- 

Ca2+-Exchanger (NCX). It was found that the protein levels of PMCA 

were significantly decreased, which was directly correlated with 

suppressed PMCA mRNA levels and declined protein activity. 

Interestingly, both NCX and SERCA were unaltered. The decrease of 

PMCA was accompanied by an increase in calcium steady-state levels 

as measured by means of GFP-based calcium sensor, chameleon, 

indicating functional relevance of PMCA preservation for calcium 

regulation in dopaminergic cells. 

Our results might help to understand the disturbance of calcium 

homeostasis in Parkinson's disease and other age-related 

neurodegenerative conditions. 

Authors: Alexander Brendel, Christian Behl, Parvana Hajieva 

_________________________________________________________ 

A16- 


Involvement of voltage-dependent anion channel 1 (VDAC-1) in H- 

Ras-mediated neuroprotection? 

In an aging society the demand for effective treatment of 

neurodegenerative diseases like Alzheimer or Parkinson disease is ever 

increasing for economical and social reasons. Using a synRas model 

expressing constitutively activated Val12Ha-Ras in neurons we here 

investigate the molecular mechanisms of its previously described 

neuroprotective phenotype (1). Quantitative proteome analysis and 

western blots revealed that the protein expression level of voltagedependent 

anion channel 1 (VDAC-1) in cortex and hippocampus of 

adult synRas mice is decreased by 70%. Alternative splicing of VDAC-1 directs its location either to the outer mitochondrial membrane (mt- 

VDAC-1) or to the cytoplasmic membrane (pl-VDAC-1). A recent study 

showed an overexpression of pl-VDAC-1in the brain of Alzheimer 

patients (2). Here we found a selectively decreased expression of pl- 

VDAC-1 in hippocampus and cortex of the synRas mice and in cultures 

of synRas derived cortical neurons. The splicing activity of VDAC-1 into 

the pl-VDAC-1 isoform was inversely correlated with Ras activity. Taken 

together, constitutive activation of Ras may change the splicing activity 

towards VDAC-1leading to a lowered expression of pl-VDAC-1protein which could contribute to the mechanism of neuroprotection in synRas 

mice and its relevance in neurodegenerative diseases will be discussed. 

1) Heumann, R., Goemans, C., Bartsch, D., Lingenhöhl, K., Waldmeier, 

P. C., Hengerer, B., Allegrini, P. R., Schellander, K., Wagner, E. F., 

Arendt, T., Kamdem, R. H., Obst-Pernberg, K., Narz, F., Wahle, P., 

Berns, H.: Transgenic activation of Ras in neurons promotes 

hypertrophy and protects from lesion-induced degeneration. J Cell Biol. 

151, 1537-48 (2000). 

2) Ramírez, C. M., González, M., Díaz, M., Alonso, R., Ferrer, I., 

Santpere, G., Puig, B., Meyer, G., Marin, R.: VDAC and ERα interaction 

in caveolae from human cortex is altered in Alzheimer's disease. Mol 

Cell Neurosci. 42(3), 172-183 (2009). 

Authors: Sebastian Neumann, Konstantin Kuteykin-Teplyakov, Rolf 

Heumann


_________________________________________________________ 

A17- 


High fat diet and IL-6 cooperatively inhibit GSK-3β activity to 

provoke hepatocellular carcinoma development 

Obesity is an aging-associated disorder that increases the incidence of 

hepatocellular carcinoma (HCC) presumably caused by the low-grade 

inflammatory state associated with obesity. Also, expression of the 

inflammatory cytokine IL-6 is accelerated during the course of obesity 

and IL-6 was shown to promote HCC development. Therefore, we 

aimed at investigating the role of IL-6 signaling in a DEN-induced HCC 

approach by employing IL-6Ra-deficient mice. Upon application of the 

carcinogen, control and mutant mice were exposed to either normal 

chow (NCD) or as a model of obesity to high fat diet (HFD) feeding. 

Disruption of the IL-6Ra protected mice from the development of HCC 

indicating the importance of IL-6 signaling in this malignancy. Strikingly, 

however, when control mice on NCD were compared with mice exposed 

to HFD, we observed significant increases in tumor number and growth 

not only in wildtype mice but also likewise in IL-6Ra-deficient mice. 

IL-6Ra knock-out mice on NCD were protected from tumorigenesis as 

IL-6-mediated phosphorylation/inactivation of GSK-3b was impaired in 

these mice. Consequently, active GSK-3b in IL-6Ra knock-out mice 

sensitised to apoptosis by phosphorylating its target the Bcl2 family 

member Mcl-1 leading to its degradation by the proteasome. Strikingly, 

aggravated PI3-kinase activity caused by HFD feeding restores both, 

inactivation of GSK-3b and Mcl-1 protein levels in IL-6Ra-deficient mice 

resulting in similar liver carcinogenesis as observed in wildtype mice. 

Thus, accelerated PI3-kinase activity in obesity is an important risk 

factor for the development of HCC. 

Authors: Sabine Gruber, Beate Straub, Jens Seeger, Hamid Kashkar, 

Peter Schirmacher, Jens Brüning, F. Thomas Wunderlich 

_________________________________________________________ 

A18- 


Functions of mitochondrial Sod1 

The respiratory chain of mitochondria releases potentially harmful 

reactive oxygen species (ROS) into the matrix and the intermembrane 

space (IMS). Several antioxidative systems contribute to ROS 

detoxification. An antioxidative key enzyme is superoxide dismutase 1 

(Sod1), a homodimeric copper-zinc enzyme. Sod1 localizes to the 

cytosol of the cell and additionally to the mitochondrial IMS. In humans, 

several mutations in Sod1 are linked to amyotrophic lateral sclerosis 

(ALS), a fatal neurodegenerative disease. One of the most occurring 

mutations is the Sod1G93A mutation. 

We used the model organism Saccharomyces cerevisiae to investigate 

the molecular mechanisms of ALS. To dissect the contribution of 

differentially localized Sod1, we constructed strains expressing Sod1 

locating to different compartments and with diverse ALS-linked 

mutations. Thereby we identified that Sod1 exclusively expressed in 

mitochondria is sufficient to complement the growth defects and ROS 

damages of a Sod1 deletion strain. Furthermore, we demonstrated that 

the Sod1G93A mutant is capable to restore the viability of a Sod1 

deletion strain in particular under mitochondrial stress conditions. 

Authors: Tina Klöppel, Christine Michels, Julia Zimmer, Johannes 

Herrmann, Jan Riemer 

36 

_________________________________________________________ 

A19- 


Inhibition of telomerase expression by androgens: A novel role of 

androgen receptor mutants for prostate cancer development 

The telomerase and especially its catalytic subunit hTERT, plays an 

important role in cell aging and cancer development. hTERT expression 

decelerates cellular senescence. Whereas most human somatic cells 

do not express telomerase activity, it is re-activated in 95 % of all cancer 

cells and therefore it is suggested as a key enzyme of cancer 

progression. Induction of telomerase is also an early event in prostate 

carcinogenesis and is considered as a marker for both primary tumors 

and metastases. Interestingly, several reports suggest that telomerase 

activity is regulated by androgens in vivo. Androgens play a central role 

in prostate development and promote prostate cancer proliferation. 

Consequently, androgen ablation is a major goal in the therapy of 

prostate cancer. Here, we show that the wild-type human androgen 

receptor (AR) inhibits the expression of hTERT and telomerase activity 

via inhibition of hTERT promoter activity in the presence of androgens. 

However, the androgen-mediated repression of hTERT is abrogated in 

human LNCaP prostate cancer cells that express a mutant AR (T877A) 

frequently occuring in refractory prostate cancer. We identified the 

underlying molecular mechanism and revealed that in contrast to the 

wild-type AR, AR-mutants are not recruited to the hTERT promoter in 

vivo. Thus, the data suggest a hormone-repressed hTERT expression 

and this reveals a novel role of hTERT in combination with AR 

mutations in prostate cancer. It also suggests to search for new AR 

antagonists that inhibit AR mediated transactivation but allow repression 

of hTERT. 

Authors: Daniela Roell, Udo Moehren, Maria Papaioannou, Christina A. 

Reeb, Annalisa Grasselli, Simona Nanni, Mohammad Asim, Ina Prade, 

Antonella Farsetti, Aria Baniahmad 

_________________________________________________________ 

A20- 


Lipofuscin-bound iron is a major intracellular source of oxidants: 

role in senescent cells 

Aging is accompanied by an intracellular accumulation of lipofuscin, a 

hydrophobic yellow-brownisch material that accumulates especially in 

the lysosomal compartment, where it can be neither degraded or 

exocytosed from the cell. Little is known whether the lipofuscin 

accumulation during aging is related to environmental conditions, as 

oxidative stress and the exact intracellular effects of lipofuscin, its 

biochemical characteristics and properties are still under discussion. 

One main factor, despite of proteasomal inhibition, of the lipofuscin 

cytotoxicity is hypothesized to be its ability to incorporate transition 

metals like copper and iron resulting in a redox active surface, able to 

catalyze the Fenton-reaction. This characteristic of lipofuscin may be 

contributing to an increased level of radical formation and oxidatively 

modified cellular components like proteins, lipids and RNA/DNA, that 

has been shown to be extensive in aging cells. 

In this study for the first time a lipofuscin-mediated formation of oxidants 

was directly shown in a model of aging fibroblasts. We could 

demonstrate that this oxidant production is independent of mitochondria 

and only existent in senescent cells. The ability of lipofuscin to produce 

oxidants is dependent on the amount of transition metals incorporated. 

Although the amount of oxidants formed by cellular lipofuscin turned out 

to be low, but chronic and thus lipofuscin is able to catalyze its own 

formation. 

Authors: Annika Höhn, Tobias Jung, Stefanie Grimm, Tilman Grune


_________________________________________________________ 

A21- 


Cockayne syndrome mutations in TFIIH impair RNA polymerase I 

transcription 

Cockayne syndrome (CS) is a devastating childhood disease with signs 

of premature aging and early death. It can be caused by the recessive 

mutation in five different genes. The gene products are involved in DNA 

repair and basal transcription mechanisms. To define the critical 

function altered in the severe disease we are investigating the function 

of CS-genes in transcription of RNA polymerase I. Do CS-mutations in 

the TFIIH subunits XPB and XPD impair RNA polymerase I 

transcription? 

Analysis of RNA polymerase I transcription in XPB/CS and XPD/CS 

cells reveal a severe reduction of ongoing transcription in vivo. Nuclear 

extracts from these cells show a distinct impairment of RNA polymerase 

I transcription in vitro that can be overcome by addition of affinitypurified 

TFIIH. "Immobilized-template" experiments demonstrate that 

TFIIH associates with the initiation complex of RNA polymerase I and 

leaves the promoter with the polymerase after start of transcription. 

Binding of TFIIH to the rDNA promoter is significantly reduced in nuclear 

extracts of TFIIH/CS cells. Density-gradient centrifugation analysis and 

co-immunoprecipitation experiments revealed that TFIIH associates 

with the enzyme after one round of transcription, indicating that the 

function of TFIIH in RNA polymerase I transcription differs from its role 

in RNA polymerase II transcription. Moreover, ChIP analysis revealed 

that TFIIH associates in addition to the rDNA promoter with geneinternal 

sequences of the rDNA, implying a role of TFIIH in transcription 

elongation of RNA polymerase I. TFIIH/CS cells have less ribosomes 

per cell, indicating that a possible reduction of the protein synthesis 

capacity of the cells could contribute to the premature aging of 

Cockayne syndrome patients. 

Authors: Anton Lebedev, Adrian Schelling, Robin Assfalg, Karin 

Scharffetter-Kochanek, Sebastian Iben 

_________________________________________________________ 

A22- 


Loss of ATP6V0A2 impairs intracellular trafficking and results in 

apoptotic cell death 

Autosomal recessive cutis laxa type 2, Debré type (ARCL2; MIM 

219200) and wrinkly skin syndrome (WSS; MIM 278250) are 

characterised by lax and wrinkled skin resulting in a progeroid 

appearance and additional manifestations. In affected individuals a 

congenital defect of glycosylation (CDG type II) on the level of the Golgi 

apparatus was observed. We could recently show that loss-of-function 

mutations in the ATP6V0A2 gene are causative for both disorders, 

which encodes the a2-subunit, an essential part of the large V-Type H+ 

ATPase protein complex. To analyse the consequences of a loss of the 

a2-subunit in more detail we investigated HeLa cells after RNAimediated 

knock-down and patient skin fibroblasts. Loss of a2 not only 

caused an impairment of retrograde Golgi-ER trafficking, but also a 

disruption of the Golgi network as well as a mislocalisation of 

endosomal vesicles. Furthermore, receptor-mediated endocytosis was 

delayed and analysis of highly glycosylated marker proteins revealed a 

glycosylation defect. We also observed strikingly increased apoptosis 

rates in a2-deficient cells. In summary, we detected multiple changes in 

vesicular trafficking after impairment of a2-mediated proton transport 

affecting the endosomal and the Golgi compartment. The resulting 

apoptosis-mediated cell loss in the affected tissues in ARCL2 patients, 

e.g. in the dermis, is likely to be a key event in the pathogenesis. 

Authors: Björn Fischer, Hardy W.L. Chan, Aikaterini Dimopoulou, 

Johannes Egerer, Danny Chan, Stefan Mundlos, Uwe Kornak 

37 

_________________________________________________________ 

A23- 


Hypothalamic and Pituitary JNK1 Signaling Coordinately 

Regulates Glucose Metabolism 

C-jun N-terminal kinase (JNK) 1-dependent signaling plays a crucial 

role in the development of obesity-associated insulin resistance. Here 

we demonstrate that JNK activation not only occurs in peripheral 

tissues, but also in the hypothalamus and surprisingly, the pituitary of 

obese mice. To resolve the importance of JNK1 signaling in the 

hypothalamic/pituitary circuitry, we have generated mice with a 

conditional inactivation of JNK1 in nestin-expressing cells (JNK1ΔNES mice). JNK1ΔNES mice exhibit improved insulin sensitivity both in the 

CNS and in peripheral tissues, improved glucose metabolism as well as 

protection from hepatic steatosis and adipose tissue dysfunction upon 

high fat feeding. Moreover, JNK1ΔNES mice also show reduced 

somatic growth in the presence of reduced insulin-like growth factor 1 

(IGF-1) concentrations, as well as increased thyroid axis activity. 

Collectively, these experiments reveal an unexpected, critical role for 

hypothalamic/pituitary JNK1 signaling in coordination of 

metabolic/endocrine homeostasis. 

Authors: Bengt Belgardt, Jan Mauer, F. Thomas Wunderlich, Marianne 

B. Ernst, Martin Pal, Gabriele Spohn, Hella S. Brönneke, Susanne 

Brodesser, Brigitte Hampel, Astrid C. Schauss, Jens C. Brüning 

_________________________________________________________ 

A24- 


Myeloid Cell-restricted Insulin Receptor Deficiency Protects 

Against Obesity-induced Inflammation and Systemic Insulin 

Resistance 

A major component of obesity-related insulin resistance is the 

establishment of a chronic inflammatory state with invasion of white 

adipose tissue by mononuclear cells. This results in the release of proinflammatory 

cytokines, which in turn leads to insulin resistance in 

target tissues such as skeletal muscle and liver. To determine the role of 

insulin action in macrophages and monocytes in obesity-associated 

insulin resistance, we conditionally inactivated the insulin receptor (IR) 

gene in myeloid lineage cells in mice (IRΔmyel-mice). While these 

animals exhibit unaltered glucose metabolism on a normal diet, they are 

protected from the development of obesity-associated insulin resistance 

upon high fat feeding. Euglycemic-hyperinsulinemic clamp studies 

demonstrate that this results from decreased basal hepatic glucose 

production and from increased insulin-stimulated glucose disposal in 

skeletal muscle. Furthermore, IRΔmyel-mice exhibit decreased 

concentrations of circulating tumor necrosis factor (TNF) α and thus 

reduced c-jun n-terminal kinase (JNK) activity in skeletal muscle upon 

high fat feeding, reflecting a dramatic reduction of the chronic and 

systemic, low-grade inflammatory state associated with obesity. This 

arises as a result of a reduced accumulation of macrophages in white 

adipose tissue due to increased susceptibility to lipid-induced apoptosis 

and a pronounced impairment of matrix metalloproteinase (MMP) 9 

expression in these cells. These data indicate that insulin action in 

myeloid cells plays an unexpected, critical role in the regulation of 

macrophage invasion into white adipose tissue and the development of 

obesity-associated insulin resistance 

Authors: Jan Mauer, Bhagirath Chaurasia, Leona Plum, Brigitte Hampel, 

Matthias Blüher, C. Ronald Kahn, Jens C. Brüning


_________________________________________________________ 

A25- 


“Dimerization inhibitors” of HIV-1 protease: from interface 

targeting peptides to triterpenes 

The subunits of the dimeric HIV protease (PR) are inactive. Peptidic 

dimerization inhibitors (DIs) were derived from PR "interface" segments 

(1,2). Further modification (lipopeptides, peptoids, ester pro-drugs, 

retro-inverso-, all-D-, cyclic peptides) improved activity (Palmitoyl- 

TyrGlu(Thyroxine): nM Ki). Some DIs also abrogate viral replication (but 

are too toxic for therapy). DIs are also active against PR mutants. Active 

site inhibitor Darunavir seems to have additional DI activity against 

unprocessed PR within GagPol. Disruptive approaches may also be 

applicable to other (ß-sheet) protein complexes. 

Method. Computer modelling (InsightII): binding energy difference PR 

bound vs. free inhibitor. 

New results. Additional triterpene inhibitors (3) are described. The 

modelling data propose a rigid scaffold with 2 carboxyls ~1.04 nm apart 

(medicagenic, quillaja acids, etc.). Three triterpene interactions to PR 

seem necessary: 3OH (+2OH) to R8, 4COO to R87 (+T26), 28COO to 

P1, H69. 

Possible further approaches. Inhibitors of PR auto-processing. By 

modelling (using a PR with 3-stranded interface, one N-terminus bound 

to the active site), a possible first inhibitor of GagPol auto-processing 

could be found. 

The cleavage and (!) ß-sheet inhibitory sequence -TLNF- and similar 

sequences occur in many natural proteins: p6* (HIV), HERV-K, 

Q8NA00, FLJ360 etc. and may cause natural AIDS protection. Also 

serpin insertion segments (a1-Antitrypsin Ac-AMFLEAIP(Nle)E-OH, 

IC50 25 μM) inhibit PR. 

Since Alzheimer aggregates also have ß-sheets, DIs for HIV PR may 

also disrupt such deposits; HIV PR DIs should be tested. In a similar 

way, other natural aggregate preventing or dissolving sequences may 

exist protecting from Alzheimer. 

Schramm, H.J. et al. (91) B.B.R.C. 179, 847. Zhang, Z.-Y. et al. (91) 

J.B.C. 266, 15591. Quéré, L. et al. (96) B.B.R.C. 327, 484. 

Authors: Hans J. Schramm, Wolfgang Schramm 

38

Poster Abstracts -C-Caloric Restriction (Mechanisms & Mimetics) 

_________________________________________________________ 

C1- 


Hormonal Regulation of the Dietary Restriction Response in C. 

elegans 

Environmental alterations can cause profound changes in organismal 

lifespan. One example is dietary restriction (DR), a reduction in caloric 

uptake without malnutrition, which can increase health and life span in 

different species across taxa, including worms, flies and rodents. 

Although a few studies have identified candidate genes required for DRinduced 

longevity in a variety of speicies, the molecular mechanisms 

remain largely elusive. In C. elegans, a widely used method of inducing 

DR involves the eat-2 mutant, which has reduced pharyngeal pumping 

and food intake. The C. elegans transcription factor, SKN-1/NF-E2, 

regulates DR-induced longevity from the pair of ASI neurons. This 

implies that downstream signals mediate the systemic physiological 

response to DR. Conceivably, this DR response could be 

communicated through hormonal signaling. If so, then specific 

hormones and their hormone receptors should be required for DRinduced 

longevity. To test this hypothesis, we are screening through 

candidate peptide hormones, G-protein coupled receptors, and nuclear 

receptors in an attempt to identify genes required for lifespan extension 

induced by DR. Currently, we have potentially identified a receptor 

necessary for DR-induced longevity and are testing for specificity using 

others forms of DR. Our studies will potentially unravel novel genes 

involved in a highly conserved biological process conferring increased 

lifespan. 

Authors: Bree Heestand, Adam Antebi 

_________________________________________________________ 

C2- 


Consequences of constitutive FoxO3 expression in neurons for 

neuronal development and adult neurogenesis 

FoxO3 is a transcription factor that is activated upon oxidative stress 

and nutrient deprivation. Inversely, it can be inactivated upon insulin and 

insulin-like signaling by Akt/PKB.We have generated transgenic mice 

with tetracycline-regulated conditional expression of a constitutively 

active allele of FoxO3 (FoxO3-CA) under the control of the brainspecific 

CaMKII promotor. Expression of the Foxo3-CA allele during 

development affected neuronal survival and, as a consequence, overall 

brain development. According to our analyses, enhanced apoptosis is 

detectable starting from day E10.5. Performing microarray expression 

analyses and Q-PCR validation, we observed an overrepresentation of 

thalamic markers and an underrepresentation of cortical markers in 

transgenic as compared to control animals at a molecular level. Our 

immunohistochemical data show a loss of progenitors in the lateral 

ventricles. Interestingly, the adult mice showed only moderate defects in 

behavioral analyses. We found a selective loss of long-term memory 

with normal learning and short-term memory. In line with this finding is 

the overall reduction of cortex thickness with no preference for a 

particular layer. However, the dentate gyrus as a relais for memory 

maintenance and a known site of adult neurogenesis is also affected by 

the genetic manipulation. Conclusion: Neural progenitors are vulnerable 

to constitutively active FoxO3-induced premature cell cycle exit and 

apoptosis. 

Authors: Uta Schmidt-Straßburger, Nina Ushmorova, Harald Maier, 

Tobias Schips, Tobias Böckers, Thomas Wirth 

39 

_________________________________________________________ 

C3- 


Ageing and calorie restriction effect the mitochondrial proteome of 

rat heart 

Recent studies show that ageing and maximum lifespan are also 

dependent on non-genetic factors. A relation between ageing and 

nutrition seems to be evidenced. The aim of our current studies is to 

unravel the effect of nutrition on the proteome. Alterations in 

mitochondrial protein quantity, composition and activity by comparing 

the mitochondrial protein profile of rats with different nutrition and 

ageing states give a hint to the mechanisms of calorie restriction and its 

influence on ageing. Due to an altered energy status during ageing the 

main focus lies on the analysis of changes in the abundance of 

complexes of the oxidative phosphorylation (OxPhos) and their 

supramolecular organisation. 

Mitochondria are isolated from rat heart tissue by differential 

centrifugation. Solubilised mitochondrial individual proteins and 

complexes are separated by blue-native and SDS polyacrylamide gel 

electrophoresis. Staining 2D gels with a fluorescent dye allows 

quantitation of supercomplexes, complexes and their subunits. Since 

previous studies showed a decrease in the quantity of mitochondrial 

ATP synthase and its subunits during ageing in other rat tissues like 

liver and brain and several other organisms like Drosophila 

melanogaster and Caenorhabditis elegans, we expect a decrease in the 

abundance of ATP synthase in rat heart as well. By in-gel and insolution 

activity tests it is determined if possible changes in the total 

amount of ATP synthase and other OxPhos complexes also correlate to 

an altered activity of the equivalent complexes. 

This research is supported by EC FP6 to N.A.D. (MiMage: Role of 

Mitochondria in Conserved Mechanisms of Ageing). 

Authors: Sandra Thilmany, Sataro Goto, Michiru Sugawa, Norbert A. 

Dencher 

_________________________________________________________ 

C4- 


Starvation persistently changes expression profiles in fat storage 

organs of the fruit fly Drosophila 

In this study we investigated whether short periods of starvation have 

long lasting effects on major fat storage organs, thus serving as 

molecular substrates for different phenomena including the catch-up 

effect or DR induced increase of lifespan. To test this hypothesis, we 

used the fruit fly Drosophila and performed transcriptome analyses of 

isolated fat bodies following different experimental regimes. Therefore, 

fat bodies of flies which were starved or which were starved and fed 

again were subjected to whole genome microarray analysis. 

Additionally, we determined the body weight of the flies during the 

experiment. Starved flies lost weight considerably and noteworthy, 

refeeding induced the catch-up phenomenon also known as “yo-yoeffect” 

in unsuccessful dieters. We found a set of approx. 800 genes 

whose expression is upregulated after 24 h of starvation. Gene ontology 

analysis revealed that they are associated with different biological 

processes, such as immune response, histolysis, oxidative 

phosophorylation, carbohydrate catabolism and autophagic cell death. 

After 48 h of refeeding, the expression of almost a quarter of them was 

still increased significantly. Our results indicate that starvation has a 

persistent impact on gene expression. In addition, this cohort of genes 

should be instrumental for identifying those genes that are critical for 

starvation-associated phenomena including the catch-up one and even 

for understanding the increased life span induced by DR. 

Authors: Renja Romey, Julia Hoffmann, Thomas Roeder

Poster Abstracts -C-Caloric Restriction (Mechanisms & Mimetics) 

_________________________________________________________ 

C5- 


The molecular mechanism of Sirtuin activation by resveratrol 

Sirtuins are protein deacetylases regulating metabolism, stress 

responses, and aging processes, and they were suggested to mediate 

lifespan extending effects of a low calorie diet. Sirtuin activation by the 

polyphenol resveratrol can mimic such lifespan extending effects and 

alleviate metabolic diseases. The mechanism of Sirtuin stimulation is 

unknown, hindering the development of improved activators. Here we 

show that resveratrol stimulates, in addition to Sirt1, a mitochondrial 

mammalian Sirtuin. We present a crystal structure of this Sirtuin with 

bound substrate peptide and resveratrol revealing its Sirtuin activation 

mechanism. Resveratrol acts as lid, closing the Sirtuin's polypeptide 

binding pocket and improving peptide binding by directly interacting with 

this substrate. Our results provide a general mechanism for Sirtuin 

activation by small molecules. They show how activators can be 

improved and tailored to a specific Sirtuin/substrate pair, providing the 

basis for development of highly specific drugs. 

Authors: Melanie Gertz, Christine Schlicker, Benjamin Fraenzel, 

Mahadevan Lakshminarasimhan, Jana Tomaschewski, Dirk Wolters, 

Clemens Steegborn 

_________________________________________________________ 

C6- 


Effect of caloric restriction on the catechin mediated life span 

extention in several C. elangans mutants 

Calorie restriction is the most robust anti-aging intervention that extends 

life-span in a wide variety of organisms. To understand better how 

caloric restriction lengthens life span, we used genetic methods and 

criteria to investigate its mechanism of action in the nematode 

Caenorhabditis elegans. Two genetically distinct mechanisms of life 

span extension are known: a mechanism involving genes that regulate 

dauer formation (age-1, daf-2, daf-16, and daf-28) and a mechanism 

involving genes that affect the rate of development and behavior (clk-1, 

clk-2, clk-3, and gro-1).The flavanol catechin is a ubiquitous metabolite 

within the plant kingdom.It is proposed that catechin modulates an 

energy-intensive stress response and repair system that results in 

reduced body length and an enhanced lifespan.We investigated effect 

of caloric restriction on catechin induced life span extention in sevreal 

C.elegans mutants (mev-1, daf-2, akt-2, nhr-8, age-1, daf-2, daf-16 etc.) 

which has longer or shorter lifespan versus to wild tiype worms. 

Lifespan tests with various stress and lifespan relevant mutant strains 

revealed that catechin induces oxidative stress resistance and 

enhances lifespan in caloric restricted worms. 

Authors: David Apkhazava, Maia Nozadze 

40 

_________________________________________________________ 

C7- 


Insulin signaling in SF1 neurons promotes diet-induced synaptic 

input reorganization of POMC-neurons and obesity development 

While steroidogenic factor (SF)1-expressing neurons of the 

ventromedial hypothalamus (VMH) serve as first order targets of the 

adipose tissue hormone leptin and are crucial for regulation of energy 

homeostasis, the role of insulin action in these cells is less well defined. 

Here we demonstrate, that insulin activates PI3-kinase signalling in 

genetically marked SF1-positive VMH neurons of control mice. Insulin 

leads to membrane hyperpolarization and reduced firing frequency in 

50% of SF1-positive cells via activation of ATP-dependent potassium 

channels. Both, insulin-stimulated PIP3-formation and insulin's ability to 

hyperpolarize and silence SF1-neurons was abrogated in mice with 

insulin receptor (IR)-deficiency restricted to SF1 expressing cells 

(IRΔSF1-mice), revealing a cell autonomous role for insulin signalling in 

SF1-neurons. Intriguingly, while body weight, adipocity and glucose 

homeostasis were indistinguishable between control and IRΔSF1-mice 

under normal chow diet, IRΔSF1-mice exhibit protection from weight 

gain, adiposity and impaired glucose intolerance when exposed to high 

fat diet. While high fat feeding activates PI3k-signaling in SF1-neurons 

of control mice, this response was attenuated in these cells of IRΔSF1mice. 

Strikingly, HFD-induced obesity is accompanied by a shift of 

synaptic input reorganization of anorexigenic POMC-neurons in the 

arcuate nucleus (ARC) of the hypothalamus towards an inhibitory tone 

and this response is abrogated in POMC-neurons of IRΔSF1-mice. 

Collectively, our experiments reveal a critical role for insulin signalling in 

VMH-neurons to regulate the activity of a VMH-ARC circuitry, whose 

veractivation contributes to the development of obesity and impaired 

glucose homeostasis upon HFD-exposure. 

Authors: Tim Kloeckener, Simon Heß, Bengt Belgardt, Paeger Lars, 

Andreas Husch, Brigitte Hampel, Harveen Dhillon, Bradford Lowell, Joel 

Elmquist, Tamas Horvath, Peter Kloppenburg, Jens Brüning,

Poster Abstracts -D-DNADamage and Stem Cells 

_________________________________________________________ 

D1- 


Gene Expression Variations in Stress-Inducible Senescence and 

Replicative Senescence in Hutchinson-Gilford Progeria 

Senescence of human cells can either be triggered by stress dependent 

mechanisms or replicative aging due to telomere attrition. To induce and 

propagate the aging process different triggers of both mechanisms may 

act together in a cooperative fashion and use overlapping signalling 

pathways. Gene expression profiling would therefore provide a better 

understanding of the mechanism of senescence and aging. 

Using Affymetrix cDNA microarray we compared the expression profiles 

of two different types of senescence models: fibroblasts, in which 

senescence was induced by UV radiation and fibroblasts from patients 

suffering from Hutchinson-Gilford progeria (HGP), a model for 

premature aging with accelerated telomere shortening. 

Although there was substantial overlap in induction/suppression of gene 

expression in functional subsets of genes, distinct sets of genes were 

altered in each group, when compared to healthy controls using 

pairwise cluster analysis to identify differences in functional pathways. 

Among other differences, mRNA expression of genes involved in 

cholesterol metabolism such as HDL metabolism was altered. These 

differential changes in gene expression could at least partially explain 

the increased HDL-dependent cholesterol efflux which has been 

observed under UV stress but not progeria cells, which show rather a 

decrease in cholesterol efflux. Thus alterations of aging pathways may 

have substantial impact for in vivo aging and development of 

atherosclerosis. 

Authors: Reinhard Voss, Janine Reunert, Kerstin Gorzelniak, Martin 

Scheel, Michael Walter 

_________________________________________________________ 

D2- 


Accumulation at the nuclear envelope identifies Annexin V as a 

potential biomarker of cellular senescence 

Cellular senescence is a permanent cell cycle arrest that can be 

induced by different mechanisms, including shortened telomeres, 

accumulation of DNA damage and oncogenic or oxidative stress. 

Senescent cells have been detected in tissues where they may exert 

anti-tumor functions and contribute to aging. Although several 

biomarkers for cellular senescence have been established (e.g. SA-beta 

Gal, p21, p16, SAHF), application of new ones should refine and 

improve the existing diagnostic tool kit. 

Using comparative mass spectrometry of in vitro aged human 

fibroblasts we observed an increase in the amount of Annexin V in cell 

nuclei, while the overall cellular amount stays unchanged. During the 

onset of cellular senescence Annexin V accumulates in the nucleus. In 

addition Annexin V accumulates at the nuclear envelope during late 

population doublings. Nuclear envelope accumulation of Annexin V was 

tightly correlated with SA-beta Gal staining. 

We also analyzed Annexin V distribution in tissue sections of human 

skin. Here, keratinocytes are Annexin V-negative in young skin but 5 to 

10 % of all cells show Annexin V staining in samples from elderly 

donors. In these cells Annexin V also accumulates in the nuclear 

envelope. 

Our results indicate that Annexin V can be used as potential new 

biomarker for cellular senescence in vitro. Annexin V staining in 

combination with other ageing markers may help to identify senescent 

cells in human skin samples. 

Authors: Karolin Klement, Christian Melle, Johannes Norgauer, Peter 

Hemmerich 

41 

_________________________________________________________ 

D3- 


Senescing human cells accumulate PML at persisting DNA damage 

foci 

PML nuclear bodies are common subnuclear structures in mammalian 

cell nuclei. Their major structural component is the promyelocytic 

leukemia (PML) protein. The PML protein and the PML nuclear bodies 

appear to be involved in DNA repair, apoptosis and senescence, but 

little is known about how PML mediates these functions.Cellular 

senescence constitutes a cell cycle arrest that limits the proliferation of 

damaged cells and is considered as a cellular counterpart of organismal 

aging. Senescence can be induced by dysfunctional telomeres, DNA 

damage and oncogenic or oxidative stress. The finding that DNA 

damage sites accumulate in senescening cells specificially indicates 

DNA double-strand breaks (DNA DSBs) and their repair as critical 

factors in the aging process. 

We have used gamma-irradiation and DNA-damaging agents to induce 

premature senescence in primary human fibroblasts. In these cells we 

have analyzed the spatial relationship between PML nuclear bodies and 

DSBs. We demonstrate that PML nuclear bodies are not associated 

with sites of successful DSB repair, but only with unrepaired DNA DSBs 

after severe damage. We could further show that the PML protein is not 

required for successful DNA repair after gamma-irradiation of human 

and murine cells. We also observed that PML specifically associates 

with accumulated DNA damage sites in replicative senescent cells. 

These observations suggest a signaling or mediator function for PML at 

unrepairable DNA double-strand breaks in aging human cells. 

Authors: Sandra Münch, Stefanie Weidtkamp-Peters, Peter Hemmerich 

_________________________________________________________ 

D4- 


DNA damage-induced-replicative senescence in gerodermia 

osteodysplastica 

Gerodermia osteodysplastica (GO) is an autosomal recessive disorder. 

Patients have wrinkly skin from birth, resulting in a prematurely aged 

appearance, and osteoporosis with high fracture susceptibility. This 

disorder is caused by loss-of-function mutations in a Golgi-localized 

soluble protein, Gorab (golgin rab6-interacting). Studying the role of 

Gorab in skin wrinkling and osteoporosis will shed light on how 

trafficking within the Golgi compartment influences the homeostasis of 

connective tissues, which show age-related changes that are partially 

recapitulated in GO. We found that the skin fibroblast from Gorab null 

mice and human GO patients showed significantly lower proliferation 

rates compared to controls. They also showed a higher percentage of 

Senescence Associated ß-galatosidase positive cells. These results 

suggest that Gorab null fibroblasts suffer from replicative senescence. 

Since genomic instability has been suggested as a cause for cellular 

senescence in various premature diseases, we investigated whether 

there is increased DNA damage in Gorab null fibroblast. We found that 

there is high percentage of Gorab null fibroblasts showing foci double 

positive for γH2AX 

and 53BP1 in the nucleus. Our results suggest that 

inactivation of Gorab results in accumulation of DNA damage in a cell, 

which may contribute to cellular senescence and premature aging in 

gerodermia osteodysplastica 

Authors: Hardy Wing Lee Chan, Björn Fischer, Johannes Egerer, Kathy 

Cheah, Danny Chan, Stefan Mundlos, Uwe Kornak

Poster Abstracts - L - Longevity and Insulin/IGF-1-Signaling 

_________________________________________________________ 

L1- 


Altered signalling from germline to intestine pushes daf-2;pept-1 

C. elegans into extreme longevity 

The insulin-like signalling (IlS) pathway is a central regulator of 

development, metabolism, stress resistance and life span in eukaryotes. 

daf-2(e1370) C. elegans with a loss-of-function mutation in the insulinlike 

receptor live twice as long as wild type animals, and the additional 

knockout of the intestinal di- and tripeptide transporter pept-1 further 

increased life span by 60% (1). In assessing the underlying molecular 

mechanisms for this phenomenon microarray-based transcriptome data 

sets of daf-2(e1370) and daf-2(e1370);pept-1(lg601) animals were 

compared with a focus on genes that showed significantly higher 

changes in expression levels in daf-2;pept-1 than in daf-2. We identified 

187 genes with at least four-fold decreased transcript levels and 170 

with more than a four-fold increase. A large fraction of the downregulated 

genes encode proteins involved in reproduction. We identified 

the DAF-9/DAF-12 signalling cascade as a prime pathway that 

mediates the longevity of daf-2;pept-1 with a strict dependence on DAF- 

16. Knockdown of either daf-9, daf-12 or kri-1 abolishes the life span 

extension daf-2;pept-1 back to that of the daf-2 mutant. Amongst the 

DAF-16 target genes numerous enzymes involved in defence of 

reactive oxygen species (ROS) were identified in daf-2;pept-1 with 

increased expression level. We demonstrate that an increased de novo 

synthesis of glutathione is necessary for the longevity phenotype of this 

strain. Thus, we have established a close interdependence of endocrine 

hormone signalling from germline to intestine as an essential element in 

the extreme longevity of C. elegans lacking a proper function of IlS and 

lacking the intestinal peptide transporter. 

(1) Meissner, B.; Boll, M.; Daniel, H.; Baumeister, R. Deletion of the 

intestinal peptide transporter affects insulin and TOR signalling in 

Caenorhabditis elegans. J Biol. Chem 2004, 279 (35), 36739-36745. 

Authors: Britta Spanier, Isabel Rubio-Aliaga, Katrin Lasch, Hao Hu, 

Hannelore Daniel 

_________________________________________________________ 

L2- 


AGE-DEPENDENT LIVER REPOPULATION BY TRANSPLANTED 

HEPATOCYTES 

The low liver repopulation efficacy of transplanted hepatocytes is 

probably due to their poor proliferative capacity linked to the age of the 

liver donors. The age-dependent proliferative potential of wild type F344 

rat hepatocytes was investigated after transplantation into old and 

young CD26-deficient F344 rat host livers. Repopulation rates were 

determined by flow cytometry and assay of CD26 enzyme activity. 

Hepatocytes isolated from either young or old donor rats formed small 

and rare clusters of donor-derived hepatocytes in senescent host livers. 

However, both hepatocytes from juvenile and from senescent donor 

livers transplanted into juvenile host livers developed cell clusters 

significantly larger and more frequently as compared with senescent 

host livers. Repopulation of juvenile host livers by old or young 

hepatocytes amounted to 20 % as compared to 2%insenescent hosts. 

No functional difference between transplanted juvenile and senescent 

hepatocytes was observed in the host liver tissue in terms of glycogen 

storage. As compared to senescent host animals, serum levels of IGF1 

were significantly higher in juvenile rats. Thus, in rats, the age of the 

recipient liver seems to be critical for the efficient repopulation by 

transplanted hepatocytes potentially involving regulation along the 

growth hormone-IGF1-axis. 

Authors: Peggy Stock, Madlen Hempel, Sabine Ebensing, Max 

Bielohuby, Martin Bidlingmaier, Bruno Christ 

42 

_________________________________________________________ 

L3- 


Mechanism of the mitogenic effect of the insulin analogue glargine 

Insulin analogues are structurally modified insulin, developed to better 

control blood glucose level of diabetic patients. However, insulin 

molecule modification may increase the affinity for the IGF-IR, a 

receptor related to proliferation. Since IGF-IR is expressed in normal 

mammary glands and overexpressed in many mammary carcinoma 

cases we studied the mitogenic effects of five insulin analogues 

(glargine, levemir, aspart, lispro and glulisine) currently approved for 

therapeutic use in diabetics, on a panel of mammary epithelial cells. 

We found that insulin glargine (Lantus®) stimulated DNA synthesis and 

proliferation in MCF-7 cells significantly stronger than regular insulin 

and other insulin analogues analysed. Glargine activated both the 

Akt/PKB and MAPK pathways significantly stronger than regular insulin. 

The use of specific MAPK inhibitors demonstrated the relevance of this 

pathway in the mitogenic effect of glargine. By siRNA knockdown, we 

showed that the proliferative ability of glargine was mainly due to 

activation of the IGF-IR. 

We further analysed serum samples from type-1 diabetic patients under 

treatment with insulin glargine or human NPH insulin. We observed that 

the serum from glargine-treated patients had a significantly stronger 

proliferative effect on MCF-7 cells compared to serum from patients 

using NPH insulin. The clinical relevance of this finding remains to be 

elucidated. 

We conclude that insulin glargine is a significantly stronger growth factor 

than regular insulin. The use of this insulin analogue by diabetics may 

have adverse effects. 

Shukla et al (2009) Endocr Rel Cancer 16:429-441. 

Mayer and Chantelau (2010) Arch Physiol Biochem. in press 

Authors: Ashish Shukla, Doris Mayer 

_________________________________________________________ 

L4- 


Ubiquitin Chain Editing Modulates Protein Homeostasis and Aging. 

Protein ubiquitylation turned out to be a key posttranslational control 

mechanism providing different fates of targeted substrates in diverse 

cellular processes such as protein quality control, cell-cycle 

progression, signal transduction and development. Therefore, it is not 

surprising that recent studies have identified a role for ubiquitin in the 

regulation of longevity. Polyubiquitylation of protein substrates required 

for proteasomal degradation involves ubiquitin-activating E1 enzymes, 

ubiquitin-conjugating E2 enzymes, ubiquitin protein E3 ligases, and 

sometimes polyubiquitylation factors (E4 enzymes). Work over the past 

20 years identified genetic programs regulating aging. Among those 

pathways, the best understood regulators are the insulin/insulin-like 

growth factor signaling (IIS) and the dietary restriction (DR) pathways. 

So far, two E3 ligases have been identified to influence the IIS-pathway, 

whereas a recent study describes the first link between ubiquitylation 

and DR. However, since the targets critical for longevity have not been 

identified yet, the role of ubiquitylation is thus completely unclear. 

Here, we identified a novel unanticipated function of the ubiquitinselective 

chaperone CDC-48 in age-related processes. Together with a 

ubiquitin hydrolase that deubiquitylates Lys48-linked polyubiquitin 

chains, CDC-48 regulates life span in C. elegans. Moreover, life span 

extension of the corresponding double mutant depends on the 

conserved Insulin/IGF signaling pathway. Thus, our data suggest that 

protein degradation and life span regulation are specifically linked by 

editing the ubiquitylation status of certain protein substrates. 

Authors: Eva Kevei, Kirsten Kuhlbrodt, Christoph Janiesch, Roja 

Barikbin, Alexandra Segref, Thorsten Hoppe

_________________________________________________________ 

L5- 


Hydroxyl group-rich flavonoids and aging processes in 

Caenorhabditis elegans. 

Dietary compounds such as plant-derived polyphenols (e.g flavonoids) 

were shown to have positive effects on lifespan and stress resistance in 

C. elegans. However, the molecular mechanisms by which flavonoids 

affect aging processes remain mostly unknown. 

We used a comparative approach by treating C. elegans with a series of 

structurally identical flavonoids that just posses an increasing number of 

hydroxyl groups attached to the B-ring. They consequently display also 

an increasing antioxidative capacity in vitro. We could show that two 

flavonoids with the highest antioxidative capacity decreased the 

mitochondrial reactive oxygen species (ROS) load by 40-70%, while the 

other flavonoids failed. This could be seen in different worm strains with 

intact as well as impaired mitochondrial function. We also assessed the 

flavonoid effects on lifespan and resistance against heat and ROS 

stress. Heat stress resistance of animals increased with the number of 

hydroxyl groups in test compounds. In case of ROS resistance and 

lifespan there was not such a structure-dependent relationship. This 

may derive from quite different effects that the compounds have on 

signaling cascades. The insulin-like signaling (IlS) cascade, the main 

effecter of stress resistance and aging in C. elegans, controls the 

transcription factor DAF-16, a key regulator of defense enzyme 

expression. Although all tested flavonoids increased nuclear 

translocation of DAF-16 up to six-fold, the phenotypic outcomes were 

quite different. Therefore, flavonoids may also affect other pathways 

than IlS in modulating lifespan and ROS resistance. However, our 

findings also emphasize the importance of the careful selection of a 

proper stressor in aging research. 

Authors: Gregor Grünz, Britta Spanier, Hannelore Daniel 

_________________________________________________________ 

L6- 


Comparison of the telomerase deletion response between two 

budding yeasts 

Cellular senescence is associated with marked changes in gene 

expression. In Saccharomyces cerevisiae senescence induced by 

telomerase depletion results in altered expression of many genes and 

metabolic reprogramming (1). To identify evolutionarily conserved 

signaling components of the telomerase deletion response (TDR) we 

have compared the TDR of S. cerevisiae with that of the budding yeast 

Kluyveromyces lactis. The latter has diverged from the Saccharomyces 

lineage before the whole genome duplication and displays a higher 

preference for respiratory metabolism. K. lactis tlc1 mutants show 

marked changes in colony morphology immediately after telomerase 

depletion induced by loss of the wild-type TLC1 gene. Its endogenous 

beta-galactosidase gene located at a subtelomeric position is frequently 

lost in senescent cells revealing a remarkable degree of genetic 

instability. We have focused on the Snf1/AMPK signaling network, 

which is central to energy homeostasis. We report that among others 

SIP4, a gene that is highly upregulated in the TDR of S. cerevisiae, is 

transiently downregulated in K. lactis immediately after loss of the TCL1 

gene. SIP4 encodes a Snf1 controlled transcription factor, which 

functions redundantly with Cat8 in S. cerevisiae but not in K. lactis. We 

propose that SIP4 regulation might reflect changes in the activity of 

Snf1 kinase activity, in response to telomerase depletion, a hypothesis 

that is currently under investigation. An influence of telomere status on 

this key regulator might also contribute to metabolic reprogramming in 

senescent cells of higher organisms. 

(1) Nautiyal S, DeRisi JL, Blackburn EH., Proc Natl Acad Sci U S A. 

(2002) 99: 9316-21. 

Authors: Caroline Machlitt, Karin D. Breunig 


43 

_________________________________________________________ 

L7- 


Repression of Foxo1 mediated signals rescues premature 

mortality in a mouse model of Alzheimer's disease. 

Alterations of glucose homeostasis or insulin receptor/insulin-like growth 

factor-1 receptor (IGF-1R) signaling are associated with 

neurodegenerative disorders such as Alzheimer's disease (AD). The 

underlying molecular mechanisms are still unclear. Previous work 

demonstrates that reduced insulin-like growth factor (IGF)-1 receptor 

expression decreases mortality in mice overexpressing the Swedish 

mutation of the Amyloid precursor protein (APPsw)1,2. Furthermore, the 

Foxo transcription factors, downstream of IGF-1Rs have been 

implicated as important regulators of metabolism, apoptosis, DNA repair 

and life span3,4. Therefore, we sought to investigate the influence of 

neuronal Foxo1 on APP-induced mortality in an established mouse 

model of AD overexpressing APPsw (Tg2676 mice). We created two 

mouse lines expressing neuron-specifically either a neuronal dominant 

active (Foxo1ADA) or a dominant negative (Foxo1DN) variant of Foxo1 

and crossed them into a Tg2576 background. The resulting genotypes 

were investigated with respect to parameters of glucose metabolism, 

growth and longevity. There were no differences in body weight and 

glucose metabolism between Tg2676Foxo1ADA, Tg2576Foxo1DN and 

Tg2576 mice. However, only the Tg2576Foxo1DN mice were protected 

against the APPsw-induced premature mortality. In contrast, the 

Foxo1ADA expressing mice even showed a tendency to die earlier than 

Tg2576 mice. Taken together, our results demonstrate a strong 

influence of Foxo1 on mortality of Tg2576 mice. Since only the 

Foxo1DN mutant protects Tg2576 mice, the involved Foxo1 target 

genes need to be repressed to mediate this protective effect. The 

identification of these genes will be an important objective of future 

research. 

1S. Freude et al., FASEB J. 23, 3315 (2009). 

2E. Cohen et al., Cell 139, 1157 (2009). 

3A. van der Horst, B. M. Burgering, Nat Rev Mol Cell Biol 8, 440 (2007). 

4M. E. Giannakou et al., Aging Cell 6, 429 (2007). 

Authors: Katharina Schilbach, Lorna Moll, Marianne Ernst, Thomas 

Wunderlich, Jens C. Brüning, Wilhelm Krone, Markus Schubert 

_________________________________________________________ 

L8- 


CERAMIDES IN THE DEVELOPMENT OF OBESITY-ASSOCIATED 

INSULIN-RESISTANCE 

Objectives: Ceramides are lipid species important for membrane 

integrity, but also involved in regulating intracellular signaling cascades 

important for cell survival or cell death. Importantly, increased ceramide 

synthesis has been shown to induce insulin resistance as seen in obese 

patients and rodents, whereas inhibition of ceramide synthesis 

ameliorates insulin resistance. There are at least six different ceramide 

synthase genes, called longevity assurance (LASS) 1-6. As each of the 

LASS enzymes generate distinct ceramide species of specific fatty acid 

length, we have analyzed lipid and especially ceramide composition of 

multiple tissues important in energy homeostasis, such as liver and 

muscle in mouse models of obesity and diabetes, as well as measured 

expression of LASS genes in these animals. 

Material and methods: Expression of LASS genes in liver (LIV) and 

skeletal muscle (SM) of ob/ob, db/db and high fat diet (HFD) mice were 

analysed by quantitative Real time PCR. Changes were confirmed at 

the level of protein expression. Ceramide concentrations and the nature 

of different ceramide species in SM and LIV of different mouse models 

were analysed by tandem mass spectrometry (LC-MS/MS). 

Results and conclusions: Real time Analysis revealed significantly 

increased expression of LASS 4,5,6 mRNA levels in SM and LASS 5 in 

LIV of ob/ob- and db/db mice. We observed an increase of ceramides, 

dihydroceramides and glycosylceramides and a decrease of 

sphingomyelins in SM and LIV of all three different mouse models. To 

further determine the role of ceramides on energy homeostasis, C2C12 

myoblasts with lentivirus mediated overexpression of each LASS gene 

have been generated. These cell lines will be subjected to mass 

spectrometry as well as functional assays on insulin-stimulated 

signaling to gain insight into the effect of the fatty acid chain length of 

ceramide species in control of ageing-associated diseases such as 

diabetes. 

Authors: Diana Maria Willmes, Susanne Brodesser, Sigrid Irlenbusch, 

Bengt Belgardt, Jens Claus Brüning


_________________________________________________________ 

L9- 


Life span modulation in C. elegans: Analysis of epithelial genes 

The nematode C. elegans is a well established model system to study 

the ageing process in a multicellular organism. The modulation of life 

span can be triggered by dietary restriction or Insulin/IGF-1 signaling. In 

contrast, the planar cell polarity pathway (PCP), which is highly 

conserved from Drosophila to vertebrates has not linked with ageing in 

C. elegans, so far. The developmental function of the PCP pathway is to 

mediate the coordinated orientation of cells or structures within the 

plane of an epithelium (e.g. in the Drosophila compound eye) or to 

regulate the organization of cellular intercalation that is required for 

morphogenesis (e.g. neural tube formation in mouse).We have 

identified a key regulator of PCP as a new modulator of life span in C. 

elegans. We show that the loss of gene function extends mean life span 

up to 40% and in addition increase thermal and oxidative stress 

resistance. Using RNA-mediated interference (RNAi) we demonstrate 

that the longevity depends on the C. elegans FOXO homolog DAF-16. 

Beside the modulation of life span we observe typical phenotypes of 

age-related genes, like slow growth and decreased fecundity. The 

molecular details concerning the crosstalk of the PCP pathway and e.g. 

the Insulin/IGF-1-like signaling need to be further addressed. 

Authors: Sebastian Honnen, Christian Büchter, Verena Schröder, 

Andreas Kampkötter, Olaf Bossinger 

44

_________________________________________________________ 

M1- 


Increased muscle PGC-1alpha expression protects from 

sarcopenia and metabolic disease during aging 

Aging is a major risk factor for metabolic disease and loss of skeletal 

muscle mass and strength, a condition known as sarcopenia. Both 

conditions present a major health burden to the elderly population. 

Here, we analyzed the effect of mildly increased PGC-1alpha 

expression in skeletal muscle during aging. We found that transgenic 

MCK-PGC-1alpha animals had preserved mitochondrial function, 

neuromuscular junctions, and muscle integrity during aging. Increased 

PGC-1alpha levels in skeletal muscle prevented muscle wasting by 

reducing apoptosis, autophagy, and proteasome degradation. The 

preservation of muscle integrity and function in MCK-PGC-1alpha 

animals resulted in significantly improved whole-body health; both the 

loss of bone mineral density and the increase of systemic chronic 

inflammation, observed during normal aging, were prevented. 

Importantly, MCK-PGC-1alpha animals also showed improved 

metabolic responses as evident by increased insulin sensitivity and 

insulin signaling in aged mice. Our results highlight the importance of 

intact muscle function and metabolism for whole-body homeostasis and 

indicate that modulation of PGC-1alpha levels in skeletal muscle 

presents an avenue for the prevention and treatment of a group of agerelated 

disorders. 

Wenz T, Rossi SG, Rotundo RL, Spiegelman BM, Moraes CT. 

Increased muscle 

PGC-1alpha expression protects from sarcopenia and metabolic 

disease during 

aging. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20405-10. 

Authors: Tina Wenz, Susana Rossi, Richard Rotundo, Bruce 

Spiegelman, Carlos Moraes 

_________________________________________________________ 

M2- 


The role of the ubiquinone pool in modulating the superoxide 

production by the mitochondrial cytochrome bc1 complex 

Production of reactive oxygen species (ROS) by the mitochondrial 

respiratory chain is considered to be one of the major causes of 

degenerative processes associated with oxidative stress. It is generally 

assumed that the ubisemiquinone intermediate formed during turnover 

at the ubiquinol oxidation center (Qo site) of the cytochrome bc1 

complex (complex III) is one of the two major sources of electrons for 

superoxide formation in mitochondria. We have shown that superoxide 

formation at the ubiquinol oxidation center of membrane-bound or 

purified cytochrome bc1 complex is stimulated by the presence of 

oxidized ubiquinone when the ubiquinol reduction center (Qi site) is 

blocked (1). This indicated that the electron is transferred onto oxygen 

from reduced cytochrome bL via ubiquinone in a reverse reaction rather 

than during the forward Q-cycle reaction. In intact rat heart mitochondria 

respiring on succinate, inhibitors (e.g. malonate, TTFA) of the 

succinate:ubiquinone oxidoreductase (complex II) stimulated 

mitochondrial ROS production at the Qo site of complex III under 

conditions of oxidant-induced reduction; this stimulation was greatly 

enhanced by uncoupling. We conclude that cytochrome bc1 complex 

linked ROS production is promoted by a partially oxidized rather than by 

a fully reduced ubiquinone pool. This may affect the production of 

deleterious ROS as well as ROS involved in cellular redox signaling. 

(1) Dröse, S., and Brandt, U. (2008). J. Biol. Chem. 283, 21649-21654. 

Authors: Stefan Dröse, Ulrich Brandt 

Poster Abstracts -M-Mitochondrial Control of Aging 

45 

_________________________________________________________ 

M3- 


Age-dependend kynurenylation of a specific tryptophan residue in 

the ATP synthase alpha subunit of Podospora anserina 

Post-translational modifications of proteins play a crucial role at 

numerous biochemical and physiological processes. Reactive oxygen 

species (ROS) cause accumulation of oxidative damage in ageing cells 

as proposed by the free radical theory of ageing and lead to protein 

carbonylation and oxidation. The conversion of tryptophan to hydroxy 

tryptophan, N-formyl kynurenine and kynurenine by ROS is an 

interesting post-translational modification to analyze, with respect to 

ageing. Mitochondrial membranes from juvenile and senescent cultures 

of the fungus P. anserina are solubilized with the nonionic detergent 

digitonin and separated according to their molecular mass by blue 

native polyacrylamide gel electrophoresis (BN-PAGE), whereby multisubunit 

(membrane-) proteins, (membrane-) protein supercomplexes 

and interacting proteins are kept in their native state. Bands of the ATP 

synthase monomer and dimer are cut out of the gel, undergo tryptic 

digestion and are analyzed by mass spectrometry. With this 

experimental setup it was possible to detect kynurenylation of one 

specific tryptophan residue of the alpha subunit of P. anserina ATP 

synthase, although it contains three residues of this amino acid. 

Furthermore three different oxidation stages of this tryptophan residue 

are found - hydroxy tryptophan, N-formyl kynurenine and kynurenine. 

Quantitation of the non-modified and differently modified peptides 

shows differences between juvenile and senescent cultures as well as 

between monomeric and dimeric ATP synthase. 

Hunzinger, C. et al. J Proteome Research 5 625-633 (2006). 

Authors: Eva R. Schäfer, Ansgar Poetsch, Sascha Rexroth, Alexandra 

Werner, Heinz D. Osiewacz, Norbert A. Dencher 

_________________________________________________________ 

M4- 


Supramolecular organisation of OxPhos complexes changes 

during ageing in various brain regions to a different extent 

Analysis of the protein profile of mitochondria and its age-dependent 

alteration is a promising approach to unravel mechanisms involved in 

ageing and age-related diseases. Our studies focus on age-related 

changes of the mammalian mitochondrial proteome in rat brain, 

examined by native polyacrylamide gel electrophoresis techniques, with 

emphasis on the abundance, composition, structure and activity of 

membrane proteins and protein complexes. We studied the 

mitochondrial proteome of the largest brain region, the cortex, and two 

smaller regions, striatum and hippocampus, of two different age groups, 

4-6 and 28 months old rats. Studies of cortex mitochondria showed an 

age-related decrease in the amount of intact MFoF1 ATP synthase and 

alteration in its distribution as oligomers, which might be a clue for 

understanding the link between respiration and longevity. Also the 

abundance of OxPhos supercomplexes, which are the natural 

assemblies of the respiratory chain complexes I, III, and IV into 

supramolecular stoichiometric entities, such as I1III2IV0-3, differs 

between young and aged cortex tissue. Age-related changes in the 

supramolecular architecture of OxPhos complexes could explain 

alterations in respiratory activity and ROS production during aging. The 

results observed for the cortex will be discussed and compared to those 

obtained from hippocampus and striatum. The hippocampus behaves 

different in many aspects. 

(Supported by the EC, FP6-2003-LifeSciHealth, Integrated Project 

MiMage: "Role of Mitochondria in Conserved Mechanisms of Ageing".) 

Seelert, H., Dani, D.N., Dante, S., Hauss, T., Krause, F., Schäfer, E., 

Frenzel, M., Poetsch, A., Rexroth, S., Schwassmann, H.J., Suhai, T., 

Vonck, J., Dencher, N.A., 2009. From protons to OXPHOS 

supercomplexes and Alzheimer's disease: structure-dynamics-function 

relationships of energy-transducing membranes. Biochim Biophys Acta 

1787, 657-671. 

Authors: Monika Frenzel, Hans Rommelspacher, Michiru D. Sugawa, 

Norbert A. Dencher

_________________________________________________________ 

M5- 


Longevity, Aerobicity and the Differential Loss of Cysteine in 

Respiratory Chain Complexes 

The usage of cysteine residues in mitochondrially encoded proteins in 

long-lived animals differs significantly from that in short-lived animals: 

long-lived animals largely abstain from incorporating cysteine residues 

in a lifespan-dependent manner. To shed further light on this 

phenomenon, we have separately analyzed all respiratory chain 

complex subunits encoded by the mitochondrial DNA of 248 animal 

species. Our results indicate that complex I and complex IV subunits 

show very different cysteine incorporation patterns: the almost exclusive 

carrier of the cysteine-lifespan correlation is complex I, whereas 

cysteine depletion in complex IV is uniform in all aerobic species, thus 

unrelated to longevity, and even more distinct than complex I cysteine 

depletion. Hence, there are two seemingly uncoupled molecular 

signatures hidden in animal mitochondria to separately reflect longevity 

and aerobicity. However, both signatures are most likely attributable to 

the same causal origin, free radical chain reactions in the inner 

mitochondrial membrane. Our observations may provide some novel 

clues on the specific role of oxidative stress in the evolution of the 

respiratory chain and its impact on longevity in animals. 

Authors: Mario Schindeldecker, Bernd Moosmann 


_________________________________________________________ 

M6- 


Infrared-A radiation influences the skin fibroblast transcriptom: 

mechanisms and consequences for skin aging 

Infrared A radiation (IRA 760-1440 nm) is a major component of solar 

radiation and - similar to ultraviolet (UV) radiation - causes photoaging 

of the skin. Until now, little was known about the IRA-induced effects on 

skin and the underlying molecular mechanisms beyond the regulation of 

matrixmetalloproteinase-1 (MMP-1). Therefore we have assessed the 

IRA-induced transcriptom in primary human skin fibroblasts. The 

fibroblasts were irradiated with a single dose of IRA (860J/cm2). 

Microarray analysis revealed 599 IRA regulated transcripts. The IRA 

induced transcriptom differed from changes induced by UV. Functional 

Gene Ontology clustering revealed that the IRA response includes four 

categories: extracellular matrix, calcium homeostasis, stress signaling, 

and apoptosis. 

These results were confirmed by realtime PCR experiments analyzing 

thirteen of these genes representing these four categories. By means of 

chemical inhibitors of known signaling pathways we next show that 

besides ERK1/2, the p38-, JNK-, PI3K/AKT-, STAT3-, and IL-6 as well 

as calcium mediated signaling pathways are functionally involved in the 

IRA gene response. 

Investigating the role of reactive oxygen species, we analyzed the effect 

of the antioxidants MitoQ (mitochondrial targeted) and N-acetyl-cysteine 

(NAC) (non organelle specific) on the IRA induced gene response. NAC 

preincubation at least partially inhibited IRA induced regulation of 12/12 

genes investigated. 

Interestingly, MitoQ treatment affected IRA gene response more 

specifically, affecting 8/12 IRA sensitive genes. 

Our results show that IRA radiation is a potent modulator of gene 

expression in human skin cells with a specific pattern involving genes of 

critical importance for skin homeostasis and photoaging. A major part of 

the IRA gene response is triggered by mitochondrial, and to a lesser 

extent non-mitochondrial production of reactive oxygen species. 

Authors: Christian Calles, Maren Schneider, Filippina Macaluso, Tereza 

Benesova, Jean Krutmann, Peter Schroeder 

46 

_________________________________________________________ 

M7- 


Mitochondrial DNA copy number decreases upon ageing in the 

short-lived fish Nothobranchius furzeri 

Mitochondria are considered to play a major role during ageing. Besides 

the production of reactive oxygen species, mitochondria are thought to 

contribute to ageing through the accumulation of mitochondrial DNA 

(mtDNA) mutations and deletions. Here we have analysed the role of 

mtDNA of the teleost fish Nothobranchius furzeri during ageing. N. 

furzeri has the shortest known lifespan (3 - 8 months, depending on the 

specific strain) of a vertebrate that can be kept in captivity. 

We sequenced the entire N. furzeri mitochondrial genome and obtained 

a total length of 19,527 bp. Further analysis revealed that the control 

region is considerably extended in comparison to other vertebrate 

species and contains a second D-loop. This second D-loop is part of a 

deletion/insertion polymorphism and seems to be specific to the genus 

Nothobranchius. MtDNA deletions have been described to accumulate 

in several species with age. However, the presence of the second Dloop 

in N. furzeri seems to be independent of age. 

We determined the mtDNA copy numbers in young and old N. furzeri 

using quantitative real-time PCR and 16S rRNA-specific primers. We 

found a significant decrease of mtDNA copy numbers in muscle and 

skin with age. We also followed up mtDNA copy numbers in individual 

fish during their lifetime and could confirm the age-dependent decrease 

of mtDNA copy numbers. 

Currently, we analyse mitochondria-related genes and their expression 

levels in order to find out more about the mechanisms that are 

responsible for the reduced mtDNA copy number. Altogether, our 

findings indicate that the mtDNA and accordingly the mitochondria play 

a major role in N. furzeri during ageing. 

Authors: Nils Hartmann, Kathrin Reichwald, Claudia Lück, Michael Graf, 

Eva Terzibasi, Alessandro Cellerino, Matthias Platzer, Christoph Englert 

_________________________________________________________ 

M8- 


Prohibitins control mitochondrial integrity and protect against 

neurodegeneration 

Prohibitins comprise an evolutionary conserved and ubiquitously 

expressed family of membrane proteins. Various roles in different 

cellular compartments have been proposed for prohibitin proteins. 

Recent experiments, however, identify large assemblies of two 

homologous prohibitin subunits, PHB1 and PHB2, in the inner 

membrane of mitochondria as the physiologically active structure. 

Mitochondrial prohibitin complexes control cell proliferation, cristae 

morphogenesis and the functional integrity of mitochondria. The 

processing of the dynamin-like GTPase OPA1, a core component of the 

mitochondrial fusion machinery, has been identified as the key process 

regulated by prohibitins.Here, we used neuron-specific ablation of the 

murine Phb2 gene in vivo. Depletion of the prohibitin complex in 

neuronal tissue leads to a severe brain atrophy associated with a 

progressive neurodegeneration. Consequently, neuron-specific PHB2deficient 

mice develop behavioral impairments and premature aging 

symptoms accompanied by compromised survival. These findings 

indicate essential roles for prohibitins in neurons in vivo which will be 

discussed. 

1. Merkwirth, C. et al. Prohibitins control cell proliferation and apoptosis 

by regulating OPA1-dependent cristae morphogenesis in mitochondria. 

Genes Dev 22, 476-88 (2008). 

2. Merkwirth, C. & Langer, T. Prohibitin function within mitochondria: 

Essential roles for cell proliferation and cristae morphogenesis. Biochim. 

Biophys. Acta 1793, 27-32 (2009). 

Authors: Carsten Merkwirth, Anne Korwitz, Paola Martinelli, Hella S. 

Broenneke, Elena I. Rugarli, Thomas Langer


_________________________________________________________ 

M9- 


Prooxidant Changes to the Matrix Drive Aging 

The free radical theory of aging postulates that the production of 

mitochondrial reactive oxygen species is the major determinant of aging 

and life span. Its role in aging of the connective tissue has not yet been 

established, even though the incidence of aging-related disorders in 

connective tissue-rich organs is high causing major disability in the 

elderly. We have now addressed this question experimentally by 

creating mice with conditional deficiency of the mitochondrial 

manganese superoxide dismutase in fibroblasts and other 

mesenchyme-derived cells of connective tissues in all organs. Here we 

show for the first time that the connective tissue-specific lack of 

superoxide anion detoxification results in reduced life-span and 

premature onset of aging-related phenotypes such as weight loss, skin 

atrophy, kyphosis (curvature of the spine), osteoporosis and muscle 

degeneration. Our results provide the basis for novel connective tissuespecific 

anti-aging strategies. 

Authors: Nicolai Treiber, Pallab Maity, Matthias Kohn, Wilhelm Bloch, 

Albert C. Ludolph, Meinhard Wlaschek, Karin Scharffetter-Kochanek 

_________________________________________________________ 

M10- 


Accumulation of mtDNA deletions during aging 

Accumulation of mitochondrial DNA (mtDNA) deletions in single cells to 

relevant levels has been described in many tissues during normal 

aging. However, little is known about the molecular mechanisms 

involved in their generation and expansion over life time. In addition, it is 

unclear why some cell types preferentially accumulate these mtDNA 

alterations, such as dopaminergic neurons in the Substantia nigra of 

humans1,2. We tested the hypothesis that accumulation of 

neuromelanin, the black pigment of the S. nigra or a high catecholamine 

turnover are involved in this processes. Thus, various mouse brain 

regions were screened for mtDNA deletions: those were not found in 12 

weeks-old mice, but were detectable at 50 weeks and further increased 

with age. Deletions were most prominent in S. nigra, followed by 

striatum, cerebellum and cortex, as previously described in humans. 

Since S. nigra of mice does not contain neuromelanin, this intracellular 

protein aggregate thus can be excluded as being causative. 

Interestingly, adrenal glands displayed a 5-fold higher deletion load 

when compared to S. nigra, suggesting that catecholamine metabolism 

stimulates their generation and/or clonal expansion. 

During aging as well as in Parkinson disease, only a vulnerable subset 

of S. nigra neurons degenerate, while dopaminergic neurons from the 

VTA region are spared. To investigate this, we screened for mtDNA 

deletions in single neurons characterized by their electrophysiological 

behaviour as well as gene expression signatures. While no deletions 

could be found in single neurons of 2 week-old mice, 25 % of both VTA 

and S. nigra cells were positive for deletions in 2 years-old mice. This 

shows that mtDNA deletions alone cannot explain the difference in 

vulnerability. 

Institute of Vegetative Physiology, Center for Molecular Medicine 

Cologne (CMMC), Department II of Anatomy, Institute of Animal 

Physiology & Cologne Cluster of Excellence on Cellular Stress 

Responses in Aging-associated Diseases (CECAD), University of Köln, 

Germany 

1. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, 

Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, and Turnbull 

DM (2006). High levels of mitochondrial DNA deletions in substantia 

nigra neurons in aging and Parkinson disease. Nat. Genet. 38, 515-517. 

2. Kraytsberg Y, Kudryavtseva E, McKee AC, Geula C, Kowall NW, and 

Khrapko K (2006). Mitochondrial DNA deletions are abundant and 

cause functional impairment in aged human substantia nigra neurons. 

Nat. Genet. 38, 518-520. 

Authors: Johannes Neuhaus, Olivier Baris, Simon Hess, Peter 

Kloppenburg, Natascha Moser, Hannsjörg Schröder, Rudolf Wiesner 

47

_________________________________________________________ 

O1- 


Long-term endurance exercise reduces senescence markers and 

telomere attrition in circulating leukocytes in professional athletes 

Objective: Physical activity reduces cardiovascular morbidity and 

mortality. Aging is the major cause of cardiovascular disease. Telomeres 

and telomere-associated proteins regulate aging on the cellular level. 

Our study examined telomere biology and senescence factors in 

endurance athletes and controls without physical activity. 

Methods and Results: Peripheral blood leukocytes were isolated from 

young track & field athletes (n=32, age 20 years, running 73 km/week), 

aged athletes performing regular endurance training (n=25, age 51 

years, running 80 km/week, 35 years training history) and two control 

groups of physically inactive healthy volunteers. Telomere repeat 

amplification protocols revealed an activation of leukocyte telomerase in 

young athletes and in elderly athletes compared to controls. Western 

blots showed an up-regulation of the telomere-capping protein TRF2 in 

young as well as in aged athletes. The expression of p16 and p53 was 

reduced in aged athletes. Flow-FISH assays and real-time PCR 

measurements of leukocyte telomere length demonstrated that 

sedentary elder controls exhibited a significant reduction of leukocyte 

telomere length (FF 53%, PCR 70% vs. young controls). Importantly, 

there was a striking conservation of telomere length in aged athletes 

(FF 88%, PCR: 84% vs. young controls). 

Conclusions: Beneficial effects of exercise on telomere proteins and 

senescence markers occur in leukocytes of young track & field athletes. 

Elderly athletes with a long-term history of endurance exercise have a 

potently activated leukocyte telomerase and conserved telomere length. 

These findings improve the molecular understanding of beneficial 

vascular effects of physical activity and implicate an anti-aging effect of 

physical exercise. 

Authors: Christian Werner, Tobias Fürster, Michael Böhm, Ulrich Laufs 

_________________________________________________________ 

O2- 


Correlation of human mesenchymal stem cell characteristics with 

donor age 

Introduction: New strategies in tissue engineering favour mesenchymal 

stem cells because they are multipotent, self-renewing cells which can 

be easily isolated from various tissues. A differentiation into 

chondrocytes and osteoblasts is well established and attractive for 

regeneration of damaged cartilage and bone. In this context the 

questions arise whether prevalence of MSC and their properties change 

with the age of their donor and should MSC therapies be restricted to a 

special age group. 

Materials and Methods: MSC were isolated from bone marrow of 28 

donors of three age groups. Proliferation capacity, number of Colony 

forming unit fibroblasts and single cell cloning efficiency was 

determined. Osteogenic differentiation potential was quantified by an 

alkaline phosphatase assay, adipogenic potential by Oil Red O 

measurement and chondrogenic potential by proteoglycan- and 

collagen type II content. 

Results: The number of CFU-F obtained per total number of 

mononuclear cells of bone marrow was independent of donor age. 

Proliferation rate was significantly lower in the elderly group compared 

to the other groups. Single cell cloning efficiency was significantly 

higher in the young group compared to the elderly one (2-fold, 

p=0.025). Osteogenic and adipogenic differentiation potential was 

maintained during aging. Chondrogenic differentiation yielded no 

significant difference between the three age groups although there is a 

tendency towards less differentiation capacity in the elderly group. 

Conclusion: While fewer cells can be expanded from old MSC donors 

the multilineage differentiation capacity of these MSC is maintained 

during aging. The high donor variability can therefore not be explained 

by donor age alone and possible further factors affecting the stem cell 

characteristics will be discussed. We conclude that age is no factor 

excluding patients from stem cell therapy. 

Authors: Verena Dexheimer, Sebastian Müller, Frank Braatz, Wiltrud 

Richter 

Poster Abstracts -O-Other Free Topics 

48 

_________________________________________________________ 

O3- 


Anti-ageing mechanism of calorie restriction: Modulation of the 

mitoproteome and of ROS generation 

Dietary restriction is the most promising approach to retard ageing as well as 

the inception of age-related diseases. Since mitochondria play a crucial role 

during aging, provoked by increased oxidative stress and decline in 

functional integrity, we have analyzed changes in protein profiles of rat liver 

mitochondria, as response to ageing and to calorie restriction (CR). The 

focus of life-prolonging mechanisms of CR is minimization of free radical 

formation, by modulating the energy transduction and detoxification system. 

Specific subunits of respiratory chain complexes I and IV, critical for 

assembly and/or activity, showed significant change in abundance with lifelong 

CR, allegedly to minimize the electron leak and subsequent ROS 

formation. The ROS level decreased significantly (2.6 fold) by CR, 

concomitant with a 1.7 fold decline in monomeric complex I. The activity of 

the cytochrome c oxidase (complex IV) was reduced 2.5 fold after life-long 

CR, in line with the detected decrease in abundance of subunits II and Va 

(reversing the ageing mediated increase) and the increase (by age and CR) 

of the activity suppressor subunit VIb. On the other hand, the GSH:GSSG 

redox system and anti-oxidant enzymes as ROS quenching means did not 

change significantly. Decrease in abundance of ATP synthase subunits, 

critical for activity and assembly of complex V was analogous to the often 

observed ageing associated decline in ATP synthesis. Occurrence of 

cytochrome P450 in multiple assemblies coincided with its differential 

response to age and CR. Simultaneous existence of age-retarding and 

ageing-analogous responses of CR, which in turn could be short-term or long 

lasting, underscored the multifaceted interplay between ageing and calorie 

restriction. Acknowledgements: Supported by the European Community, EC 

FP6 contract number LSHM-CT-2004-512020, MiMage, and the Deutsche 

Forschungsgemeinschaft, grant SFB 472, to N.A.D. 

D. Dani, I. Shimokawa, T. Komatsu, Y. Higami, U. Warnken, E. Schokraie, M. 

Schnölzer, F. Krause, M. Sugawa and N. A. Dencher. Modulation of oxidative 

phosphorylation machinery signifies a prime mode of anti-ageing mechanism 

of calorie restriction in male rat liver mitochondria. Biogerontology, online 

October 2009, DOI: 10.1007/s10522-009-9254-y. 

Anne D. van Diepeningen, Marc F.P.M. Maas, Daphne H.E.W. Huberts, 

Daniël j. Goedbloed, Daniël J.P. Engelmoer, Marijke Slakhorst, A. Bertha 

Koopmanschap, Frank Krause, Norbert A. Dencher, Carole H. Sellem, Annie 

Sainsard-Chanet, Rolf F. Hoekstra and Alfons J.M. Debets. Calorie restriction 

causes healthy life span extension in the filamentous fungus Podospora 

anserina. Mech. Ageing Dev. (2010), doi:10.1016/j.mad.2009.12.002. 

Authors: Diksha Dani, Isao Shimokawa, Toshimitsu Komatsu, Yoshikazu 

Higami, Uwe Warnken, Elham Schokraie, Martina Schnoelzer, Frank 

Krause, Michiru Sugawa, Norbert A. Dencher 

_________________________________________________________ 

O4- 


The RING-finger peroxins Pex2p and Pex12p function as Ubiquitin- 

Ligases of the peroxisomal ubiquitination machinery 

The PTS1-dependent peroxisomal matrix protein import is facilitated by 

the receptor protein Pex5p. It can conceptionally be divided into (1) 

cargo recognition in the cytosol, (2) membrane docking of the cargoreceptor 

complex, (3) cargo release and (4) recycling of the receptor. 

The final step is controlled by the ubiquitination status of Pex5p. While 

polyubiquitinated Pex5p is degraded by the proteasome, 

monoubiquitinated Pex5p is destined for a new round of the receptor 

cycle. Recently, the E2-enzymes involved in Pex5p ubiquitination were 

identified as Ubc4p and Pex4p (Ubc10p), whereas the identity of the 

corresponding E3-ligases remained unknown. Here we report on the 

identification of the E3-ligases that are responsible for the ubiquitination 

of peroxisomal protein import receptor Pex5p. 

It is demonstrated that each of the three RING-peroxins Pex2p, Pex10p 

and Pex12p exhibit ubiquitin-protein isopeptide ligase activity. The three 

proteins differ in their specificity. Our results show that Pex2p mediates 

the Ubc4p-dependent polyubiquitination whereas Pex12p facilitates the 

Pex4p-dependent monoubiquitination of Pex5p. 

The identification of the E3-enzymes completes the peroxisomal 

ubiquitination cascades acting on Pex5p. 

Authors: Fouzi El Magraoui, Harald W. Platta, Bastian E. Bäumer, 

Daniel Schlee, Wolfgang Girzalsky, Ralf Erdmann

_________________________________________________________ 

O5- 


The Role of oxygen signaling in oncogene-induced senescence 

Cellular senescence limits the replicative lifespan of mammalian cells 

thereby functioning as a tumor suppressor mechanism. Moreover, 

senescent cells are assumed to contribute to organismal aging via a 

secretory phenotype. Although many triggers and signaling pathways 

inducing senescence are known, their interactions and impacts that 

finally cause the cell cycle arrest are less understood. Since oxidative 

stress triggers senescence, too and participates in normal aging and the 

development of cancer, experiments to study the links between oxygen 

signaling, oncogenesis and celluar senescence were performed. 

Therefore, a cellular model of oncogene-induced senescence was 

developed. Upon hormone induced overexpression of Raf-1, fibroblasts 

arrest the cell cycle, display a distinctive morphology and stain positive 

for senescence-associated β-galactosidase 

and senescence-associated 

heterochromatin foci. 

Firstly, the oxygen-sensing proteins HIF (hypoxia inducible factor) prolyl 

hydroxylases (PHDs) were studied. In fact, senescent fibroblasts are 

not able to adapt to hypoxic conditions by upregulation of HIF, while 

PHDs seem to be slightly stronger expressed in senescent cells. 

Moreover, chemical inhibition of PHDs delays the development of 

senescence markers. These preliminary results are confirmatory to 

literature data from human tissue and demonstrate that this cellular 

model can be further used to study the role of oxygen signaling during 

oncogene activation and senescence. 

Authors: Claudia Gey, Carl Mann, Reinhard Depping 


49 

_________________________________________________________ 

O6- 


AGING ASSOCIATED HEMATOPOIETIC STEM CELL 

DEPOLARIZATION DEPENDS ON THE RHO FAMILY GTPASE 

CDC42 

Aged hematopoietic stem cells (HSCs) are unable to contribute 

efficiently to hematopoiesis since they are impaired in their ability to 

self-renew and to differentiate into red blood and lymphoid cells. These 

functional differences between HSCs from young and aged individuals 

are partially intrinsic to aged HSCs. The physiologic mechanisms of 

HSC aging are still poorly understood, precluding a rational approach to 

ameliorate their altered function. We recently described that aged Lin-ckit+sca1+ 

cells (primitive early progenitor cells) are located at sites 

more distant from the endosteum and present with significantly 

increased protrusion movement in vivo compared to young cells. These 

phenotypes correlated with increased activity of the small Rho GTPase 

Cdc42 in the bone marrow of aged mice and with the finding that mice 

with constitutively active Cdc42 display a premature aging like 

syndrome. Therefore, we hypothesize that critical changes in 

hematopoietic stem cell function with aging are a consequence of the 

increased activity of Cdc42 in aged HSCs. The augmented level of 

Cdc42-GTP might influence and impair polarity maintenance, 

cytoskelatal dynamics, and adhesion molecule expression and 

localization in aged HSCs. 

To test this hypothesis we isolated HSCs (sorted as Lin-ckit+sca1+CD34-Flk2-) 

from bone marrow of young (3-4 months) and 

aged (21-26 months) C57Bl/6 mice and analyzed expression and 

localization of Cdc42 together with actin, tubulin and several polarity 

proteins and adhesion receptors. Single-cell immunofluorescence 

staining showed that Cdc42 and tubulin localize in a highly polarized 

way in 65% of young HSCs. Co-immunostaining of Cdc42 and tubulin 

revealed that both proteins accumulate at the same pole of the cell in 

young HSCs, while only 19% of aged HSCs show a polar distribution of 

Cdc42 and tubulin. Moreover, we detected that in young HSCs the 

adhesion molecule NCam2, whose expression has not been described 

in HSCs so far, was localized in a highly polarized fashion at the 

Cdc42/tubulin marked pole on the membrane, whereas it was nonpolarized 

in aged HSCs. Analyzing the localization of additional known 

polarity proteins confirmed that in general, young HSCs present with a 

polarized cell organization, while aged HSC are apolar. 

Pharmacological inhibition of Cdc42 activity by CASIN, a small molecule 

Cdc42 activity-specific inhibitor, significantly decreased the percentage 

of young HSCs polarized for Cdc42, tubulin and NCam2, and reverted 

the apolar distribution of Cdc42, tubulin, and NCam2 of aged HSCs in a 

dose-dependent manner. This demonstrates that Cdc42 activity controls 

the polar localization of Cdc42 in HSCs and that polarization of both 

tubulin and NCam2 depend on Cdc42 activity. We are currently 

investigating the role of elevated Cdc42 activity in aged HSCs with 

respect to stem cell polarity and function. Collectively these data 

support a role for altered HSC polarity controlled by Cdc42 activity in 

the regulatory mechanism of mouse HSC aging. 

Authors: Maria Carolina Florian, Deidre Daria, Hubert Schrezenmeier, 

Mark Rojewski, Marie-Dominique Filippi, K. Lenhard Rudolph, Karin 

Scharffetter-Kochanek, Yi Zheng, Hartmut Geiger

_________________________________________________________ 

O7- 


Regulation of AP-1 activity in glucose-stimulated insulinoma cells 

The transcriptional activity of AP-1 has been analyzed in glucosestimulated 

INS-1 insulinoma cells using a chromosomally embedded 

AP-1-responsive reporter gene. We show that AP-1 activity was 

significantly elevated in glucose-treated INS-1 cells. Preincubation of 

the cells with nifedipine or expression of the Ca2+ binding protein 

parvalbumin in the cytoplasm of INS-1 cells reduced AP-1 activity. Thus, 

activation of L-type Ca2+ channels and an elevated cytoplasmic Ca2+ 

concentration are crucial to connecting glucose stimulation with 

enhanced AP-1 activity. Expression of dominant negative forms of A- 

Raf, MKK4 or MKK6 and pharmacological inhibition of MEK and p38 

revealed that extracellular signal-regulated protein kinase, p38 and c- 

Jun NH2-terminal protein kinase participate in the upregulation of AP-1 

activity. Expression of dominant-negative mutants of c-Jun and Elk-1 

reduced AP-1 transcriptional activity in INS-1 cells indicating that c-Jun 

and ternary complex factors are involved in the regulation of AP-1 

activity in glucose-stimulated insulinoma cells. 

Isabelle Müller, Gerald Thiel, Department of Medical Biochemistry and 

Molecular Biology, University of Saarland Medical Center, D-66421 

Homburg, Germany, E-mail: ellebasi_de@yahoo.de 

Authors: Isabelle Müller, Gerald Thiel 

_________________________________________________________ 

O8- 


Signal transduction of pregnenolone sulfate in insulinoma cells: 

Activation of Egr-1 expression involving voltage-gated Ca2+ 

channels, ERK and ternary complex factors 

The neurosteroid pregnenolone sulfate acts on the nervous system by 

modifying neurotransmission and receptor functions, thus influencing 

synaptic strength, neuronal survival and neurogenesis. Here we show 

that pregnenolone sulfate induces a signaling cascade in insulinoma 

cells leading to enhanced expression of the zinc finger transcription 

factor Egr-1 and Egr-1-responsive target genes. Pharmacological and 

genetic experiments revealed that influx of Ca2+ ions via voltage-gated 

Ca2+ channels, elevation of the cytosolic Ca2+ level and activation of 

ERK are essential for connecting pregnenolone sulfate stimulation with 

enhanced Egr-1 biosynthesis. Expression of a dominant-negative 

mutant of Elk-1, a key regulator of gene transcription driven by a serum 

response element, attenuated Egr-1 expression following stimulation, 

indicating that Elk-1 or related ternary complex factors connect the 

transcription of the Egr-1 gene with the pregnenolone sulfate-induced 

intracellular signaling cascade elicited by the initial influx of Ca2+. The 

newly synthesized Egr-1 was biologically active and bound under 

physiological conditions to the regulatory regions of the Pdx-1, synapsin 

I, and chromogranin B genes. Pdx-1 is a major regulator of insulin gene 

transcription. Accordingly, elevated insulin promoter activity and 

increased mRNA levels of insulin could be detected in pregnenolone 

sulfate-stimulated insulinoma cells. Likewise, the biosynthesis of 

synapsin I, a synaptic vesicle protein that is found at secretory granules 

in insulinoma cells, was stimulated in pregnenolone sulfate-treated 

insulinoma cells. These data show that pregnenolone sulfate induces a 

signaling cascade in insulinoma cells that is very similar to the signaling 

cascade induced by glucose. 

Authors: Sabine Mayer, Isabelle Müller, Gerald Thiel 


50 

_________________________________________________________ 

O9- 


Outcome of the mitochondrial Atp8 mutation on betacell function 

and diabetessusceptibility 

The conplastic mouse strains B6mtFVB and NODmtFVB are carrying a 

mitochondrial mutation at the Atp8 gene (subunit 8 ATP-synthase 

complex). It was the aim of the study to characterise the effect of the 

Atp8 mutation on functional betacell parameters in the autoreactive 

background of the NOD or the diabetesresistent background of the B6 

mouse. The NODmtFVB mice showed a significant higher diabetes 

♀ ♂ 

incidence compared to the NOD strain ( : 85% vs. 65%; : 37% vs. 

10%). The oxygen consumption in isolated mitochondria was 

significantly higher in NODmtFVB but not significantly different in 

B6mtFVB compared to its control strain B6mtAKR. NODmtFVB 

mitochondria had significantly higher ATPase activity than NOD 

mitochondria. NODmtFVB and B6mtFVB mitochondria produced 

significantly higher amounts of mitochondrial H2O2. A 24 hour 

exposition to 30 mmol glucose showed a significant reduction of 

glucose stimulated insulin secretion in isolated islets of B6mtFVB mice 

even if there were no significant differences in ATP/ADP ratio. So we 

postulate that the mutation of the Atp8 gene results in a significant 

increase of reactive oxygen species (ROS). This leads, irrespective of 

stable ATP/ADP ratio and respiration, to betacell dysfunction after 

glucose exposition and to a higher diabetes susceptibility in conplastic 

NOD. Our data supports the critical examination of classical 

mitochondrial parameters for betacell function and destruction in 

comparison to nutritive stressors. 

Authors: Heike Weiss, Christiane Koch, Lena Wester-Rosenloef, Saleh 

Ibrahim, Markus Tiedge 

_________________________________________________________ 

O10-DOI: 

10.3288/contoo.paper.768 

Nanoparticles Induce Reproductive Senescence In Caenorhabditis 

elegans 

While expectations and applications of nanotechnologies grow 

exponentially, little is known about interactions of engineered 

nanoparticles with multicellular organisms. Here we propose the 

transparent roundworm Caenorhabditis elegans as a simple but 

anatomically and biologically well defined animal model that allows for 

whole organism analyses of nanoparticle-bio-interactions. Microscopic 

techniques showed that fluorescently labelled nanoparticles are 

efficiently taken up by the worms during feeding, and translocate to 

primary organs such as epithelial cells of the intestine, as well as 

secondary organs belonging to the reproductive tract. The life span of 

nanoparticle-fed Caenorhabditis elegans remained unchanged, 

whereas a reduction of progeny production was observed in silicananoparticle 

exposed worms versus untreated controls. This reduction 

was accompanied by a significant increase of the 'bag of worms' 

phenotype that is characterized by failed egg-laying and usually occurs 

in aged wild type worms. Experimental exclusion of developmental 

defects suggests that silica-nanoparticles induce an age-related 

degeneration of reproductive organs, and thus set a research platform 

for both, detailed elucidation of molecular mechanisms and high 

throughput screening of different nanomaterials by analyses of progeny 

production. 

Pluskota A, Horzowski E, Bossinger O, von Mikecz A (2009) In 

Caenorhabditis elegans Nanoparticle-Bio-Interactions Become 

Transparent: Silica-Nanoparticles Induce Reproductive Senescence. 

PLoS ONE 4(8): e6622. doi:10.1371/journal.pone.0006622 

Authors: Adam Pluskota, Eva Horzowski, Olaf Bossinger, Anna von 

Mikecz

_________________________________________________________ 

O11- 


Identification and Quantification of microRNA Expression by High- 

Throughput-Sequencing in the short-lived Fish Nothobranchius 

furzeri 

MicroRNAs (miRNAs) represent an abundant and highly conserved 

family of endogenous single-stranded small RNA molecules of 

approximately 20-25 nucleotides in length. The evolutionary 

conservation of miRNAs in distantly related species indicate their role 

as major regulators of different processes like developmental timing, 

cellular differentiation, apoptosis, and signalling pathways. Here, we use 

miRNA Sequencing with the Illumina GAIIx, to analyze the influence of 

aging on miRNA expression in the model-organism Nothobranchius 

furzeri. The annual killifish N. furzeri has a very short lifespan. The 

inbred line from the terra-typica (GRZ) can reach an age of 3.5 months 

and the wild-derived strain MZM 04-10 can live up to 10 months. It 

follows from above that these strains can be used for comparative 

studies of aging. Our first results show, that we are able to identify and 

quantify miRNAs in this species using miRNAs from other vertebrate 

species as reference. This technique seems well suited to analyze agedependent 

expression of miRNAs in N. furzeri. 

Authors: Mario Baumgart, Marco Groth, Matthias Platzer, Alessandro 

Cellerino 

_________________________________________________________ 

O12-DOI: 


Redox Signalling Changes during Senescence in Human Dermal 

Fibroblasts 

The free radical theory of ageing postulating reactive oxygen species 

(ROS) drive ageing is still under debate. We used 2D fluorescence 

difference gel electrophoresis and mass spectrometry of senescent 

fibroblasts to address the questions whether imbalanced expression of 

antioxidant enzymes leads to oxidative stress, and if so, what the 

predominant oxygen species are. We found manganese superoxide 

dismutase (SOD2) to be 13-fold increased while peroxiredoxins 2, 5, 6 

revealed only small changes. This imbalance in H2O2 generation and 

detoxification may result in redox imbalance. Increases in SOD2 

expression and activity were confirmed using immunostaining/blot and 

activity assay. DHE loading revealed a 2-fold increase in ROS in 

senescent fibroblasts. To specify the ROS, adenoviral transduction with 

the H2O2 sensitive HyPer and the O2-. detecting MitoSox was used. 

We found a significant increase in mitochondrial H2O2 and a decrease 

in O2.- in senescence. SOD2 overexpressing senescent fibroblasts 

showed a 3-fold increase in expression and activity of interstitial 

collagenase/MMP-1 responsible for collagen degradation during skin 

ageing. To study the role of H2O2 in the AP-1-dependent MMP-1 

induction, fibroblasts were transfected with MMP-1 promoter constructs. 

A 4-fold higher transactivation of AP-1 was detected in stably SOD2 

overexpressing fibroblasts. Collectively, we have found that enhanced 

SOD2 activity in senescent fibroblasts via an unbalanced H2O2 

overproduction induces MMP-1 most likely mediated by AP-1. Targeting 

strategies for fibroblasts may hold considerable promise to rescue redox 

balance and prevent or treat connective tissue degradation in skin 

ageing. 

Grant: EU-IP PROTEOMAGE [FP6-518230] 

Authors: Florentina Ferchiu, Anca Sindrilaru, Lea Sante, N. Treiber, R. 

Huber, Elke Nüsseler, Adelina Rogowska-Wrezescinska, P. Roepstorff, 

P. Maity, S. Iben, O. Toussaint, Stefan Kochanek, M. Wlaschek, Karin 

Scharffetter-Kochanek 


51 

_________________________________________________________ 

O13-DOI: 


Neuraminidase 3 (Neu3) is critically involved in the initiation of the 

UVA stress response 

Previously, we have shown that in primary human epidermal 

keratinocytes (HNK) UVA-induced signal transduction is initiated in cell 

membrane lipid rafts where ceramides are being generated. This leads 

to activation of Src kinases, transcription factor AP2 and increased 

expression of ICAM-1. Modulation of the lipid composition of rafts on a 

molar basis revealed that approx. 60% of the ceramides formed as the 

consequence of non-enzymatic hydrolysis of sphingomyelin (SM). In the 

present study we have searched for the mechanism responsible for the 

remaining 40%. Depletion of caveolin-1 by retroviral knockdown in 

HaCaT cells in vitro or knockout of caveolin-1 in mice in vivo rendered 

cells/mice completely unresponsive towards UVA radiation. Interestingly, 

this unresponsiveness was associated with an altered expression of the 

raft associated Neu3, capable of degrading GM3. Accordingly, UVA 

radiation increased Neu3 activity 2-fold in HNK and 3-fold in HaCaT 

cells and this was associated with a 40% degradation of GM3 in rafts. 

Also, complete inhibition of UVA-induced GM3 degradation with the 

Neu3 inhibitor DANA caused an approx. 40% inhibition of UVA-induced 

(i) ceramide formation, (ii) activation of Src, (iii) activation of AP2 and 

(iv) upregulation of ICAM-1 expression. These results indicate that in 

addition to non-enzymatic degradation of SM, Neu3 mediated 

degradation of gangliosides is an initiating event in the UVA stress 

response. Accordingly, in caveolin-1 knockdown cells neither 

degradation of SM nor of GM3 was observed after UVA irradiation. Our 

studies also show for the 1st time that Neu3 is critically involved in the 

UV stress response and represents a novel target for prevention of UVinduced 

skin damage. 

Authors: Susanne Grether-Beck, Rehab Walli, Zippora Kohne, Heidi 

Brenden, Ingo Felsner, Marc Majora, Joachim Füllekrug, Teimo 

Kurzchalia, Jean Krutmann

_________________________________________________________ 

O14-DOI: 


MicroRNA modulators of C. elegans aging and healthspan 

Identification and characterization of genes involved in promoting 

healthy aging is a key focus of aging biology and offers a dual 

advantage of improving the period of healthy aging as well as extending 

understanding the cellular processes involved in delaying age-onset 

diseases. MicroRNAs (miRNAs) are a newly appreciated class of 

conserved [1] regulatory non-coding RNAs that are implicated in 

fundamental and diverse biological processes, including diseases of 

aging like cancer and neurodegeneration. miRNAs have been proposed 

to buffer against variation and stochastic events in order to maintain 

biological robustness. Age-related loss of miRNA-mediated regulation 

may lead to large and detrimental deviations from robustness that are 

characteristic of aging. Indeed, in a genome wide survey of how miRNA 

expression changes during adult life, we find that about half of C. 

elegans miRNAs are significantly regulated during aging (most of them 

are down-regulated)[2] 

In an effort to determine whether miRNAs may modulate aging in 

general, we are currently conducting the first comprehensive screen to 

identify miRNAs that modulate the aging process. Assays that measure 

the accumulation of age-pigments (fluorescent lipofuscin and advanced 

glycation end products) in whole animals have shown that 17 mutant 

miRNA strains exhibit abnormal levels compared to same age wildtype 

animals during early adulthood (Day 4). Since age pigments are thought 

to reflect the physiological age rather than the chronological age[3], 

these miRNAs may be responsible for maintaining physiological 

homeostasis through life. 5 tested strains also exhibited significantly 

altered age pigment levels at mid-late (Day 9) or late (Day 11) 

adulthood. 4/5 age-regulated miRNAs (mir-1, mir-34, mir-71, mir-238) 

also showed a significant decline in swimming prowess compared to 

wild type animals at late age (Day 10), although their swimming in early 

adulthood is similar to wild type. Significantly, these mutants also 

accumulate higher age pigments early in life, perhaps indicating that a 

"poor" start leads to decline in integrity later in life. We have also 

identified a few miRNA mutants that have lower age pigment levels late 

in life. Some of these have multiple indicators of strong healthspan. 

In conclusion, some miRNAs may play an important role in maintaining 

homeostasis and general integrity of the aging animal. Deciphering the 

gene networks that they regulate may suggest new strategies for 

positive healthspan intervention. 

Ibanez-Ventoso, C., Vora, M. & Driscoll, M. Sequence relationships 

among C. elegans, D. melanogaster and human microRNAs highlight 

the extensive conservation of microRNAs in biology. PLoS ONE. 2008; 

3(7): e2818. 

Ibanez-Ventoso, C., Yang, M., Guo, S., Robins, H., Padgett, R.W. & 

Driscoll, M. Modulated microRNA expression during adult lifespan in C. 

elegans. Aging Cell 5, 235-246 (2006). 

Gerstbrein, B., Stamatas, G., Kollias, N. & Driscoll, M. In vivo 

spectrofluorimetry reveals endogenous biomarkers that report 

healthspan and dietary restriction in Caenorhabditis elegans. Aging Cell 

4, 127-137 (2005). 

Authors: Mehul Vora, Mitalie Shah, Carolina Ibanez-Ventoso, Marton 

Toth, Jian Xu, Monica Driscoll 


52 

_________________________________________________________ 

O15-DOI: 


Proteome analysis of senescence-associated protein changes in 

cultured human fibroblasts using a label-free mass spectrometry 

approach 

Stromal fibroblasts are a major target of the aging process in various 

organs including the skin. To identify novel proteins potentially involved 

in stromal aging, we performed a label-free proteomics approach using 

recently introduced ESI-Q-TOF mass spectrometer (maXisTM, Bruker 

Daltonics, Germany) in combination with ProgenesisTM software 

(Nonlinear Dynamics, United Kingdom). This approach was successfully 

applied for the comparison of young versus old (senescent) cultured 

primary human dermal fibroblasts harbored at different in vitro passages 

(passages 7, 13, 23 and 24). Altogether more than 12,000 features 

were detected in all LC-MS/MS runs. The differential analysis of the LC- 

MS/MS runs with the ProgenesisTM software revealed 115 peptides (p 

< 0.05 and average ratio above 1.5), corresponding to 60 distinct 

proteins, that were differentially regulated between early and late 

passages of primary human dermal fibroblasts. A comparative analysis 

of the same samples using 2D-DIGE followed by MALDI-TOF mass 

spectrometry revealed 19 distinct proteins showing significant 

differential expression. Six of these differentially regulated proteins were 

identified with both methods, i.e., LC-MS and 2D-DIGE. Taken together, 

our proteomic profiling approaches allowed for the detection of novel 

senescence-associated changes in protein expression and protein 

isoform composition in human fibroblasts that may be of relevance for 

stromal aging. 

Authors: Daniel Waldera, Ana-Maria Florea, Sebastian Link, Birgit Korte, 

Barbara Sitek, Helmut Meyer, Guido Reifenberger, Kai Stühler 

_________________________________________________________ 

O16- 


Gene regulation by natural antisense transcripts during sperm 

development and ageing: An example of antagonistic pleiotrophy? 

Natural antisense transcripts (NATs) have recently emerged as 

important regulators of gene expression in eukaryotes. Our research 

focuses on genomic and mechanistic aspects of NATs and aims at 

understanding the biological role of antisense transcription. We used 

Affymetrix gene arrays to establish a general expression pattern of 

NATs and found predominant expression in haploid spermatids. Low 

intensity signals were also observed in other tissues and usually 

correlated with expression of the cognate sense transcript. Interestingly, 

we detected that the presence of NATs correlates with genes that show 

random monoallelic expression. Investigations into the mechanism of 

how NATs can influence gene function suggested that transiently coexpressed 

sense and antisense transcripts are processed into short 

endogenous RNAs (endo-siRNAs). A key step in this process is the 

selection of one specific strand -sense or antisense- from the doublestranded 

precursor. The endo-siRNAs may then silence the 

complementary transcript. Under physiological conditions, endo-siRNAs 

complementary to the antisense transcript will be selected and the 

protein-coding sense transcript stays active. We hypothesise that 

mutations in the protein coding sense gene can influence strand 

selection and trigger the silencing of the affected transcript (1). 

Accordingly, NATs would contribute to protecting bi-directionally 

transcribed genes against mutagenic insults.The general expression 

pattern of NATs combined with their suggested biological role has 

intriguing implications: in haploid cells (spermatids), NATs will contribute 

to silencing mutated genes, leading to increased selective pressure and 

eventually a positively selected cell population. In diploid cells, recurrent 

mutagenic impacts will lead to a progressive accumulation of randomly 

silenced alleles and eventually to completely silenced loci and 

senescence. 

(1) Carlile M, Swan D, Jackson K, Preston-Fayers K, Ballester B, Flicek 

P, Werner A. Strand selective generation of endo-siRNAs from the 

Na/phosphate transporter gene Slc34a1 in murine tissues. Nucleic Acid 

Research 37: 2274-2282, 2009. 

Authors: Andreas Werner, Mark Carlile, Dan Swan

_________________________________________________________ 

O17-DOI: 


Mitotic spindle stress as a major trigger of premature senescence 

Mitotic spindle defects caused by microtubule-interfering (MT) drugs like 

paclitaxel are potent trigger of mitotic cell death or p53-dependent postmitotic 

cell cycle arrest in the case of aberrant cell division. Here we 

tested the role of TACC3 (transforming acidic coiled coil 3), a mitotically 

expressed centrosomal protein and major regulator of mitotic MT 

dynamics, as a potentially novel molecular target in the induction of 

premature senescence. Interestingly, knock-down of TACC3, in contrast 

to treatment with paclitaxel, failed to induce a cell death response in 

immortalized MCF10a epithelial cells or MCF7 cells even after reexpression 

of caspase 3. Consistent with this, down-regulation of 

TACC3, but not paclitaxel treatment, led to a progressive loss of the 

pro-apoptotic Bcl-2 family member Bim that links microtubule integrity 

and mitotic cell death. Rather, TACC3-depleted cells arrested in G1 

through a cellular senescence program characterized by the 

upregulation of p53 and nuclear p21WAF, downregulation of pRb levels, 

formation of HP1g (pSer83) positive senescence-associated 

heterochromatic foci (SAHF), and increased senescence-associated bgalactosidase 

activity. Using gene expression profiling we observed an 

upregulation of various senescence-associated transcripts including 

PML and SP110 as well as downregulation of ERK signaling and c-FOS 

expression. Interestingly, the onset of senescence through TACC3 

depletion was strongly accelerated by low paclitaxel treatment in. Thus, 

our results establish mitotic spindle stress as efficient inducer of 

premature senescence. 

Authors: Stephan Schmidt, Leonid Schneider, Frank Essmann, Olga 

Modlich, Ion C. Cirstea, Fabian Kuck, Antje Lindecke, Anja Kletke, 

Reiner U. Jähnicke, Helmut Hanenberg, Karl Köhrer, M. Reza 

Ahmadian, Klaus Schulze-Osthoff, Bernd Nürnberg, Roland P. Piekorz 

_________________________________________________________ 

O18- 


DNA damage signaling and ROS production in IL-1beta induced 

senescence in HUVEC 

Aging Basic Research Group, Molecular Biology and Biochemistry 

Research Center for Nanomedicine, CIBBIM-Nanomedicine, Vall 

d'Hebron University Hospital. Barcelona, Spain. 

Cellular senescence is a state in which cells lose their ability to 

proliferate and can be triggered by various stress stimuli including 

telomere erosion, DNA damage, oncogenic and inflammatory signaling. 

Inflammation and inflammatory signaling plays a key role in cellular 

aging, age related diseases and cancer. Role of endothelial cells in 

inflammation is also crucial since they serve as sensors and 

transducers of signals. In the present study, we show Interleukin-1beta 

(IL-1 β), 

a potent cytokine in mediating inflammatory response, induced 

premature senescence in HUVEC's as confirmed by G1/G2 cell cycle 

arrest, up regulation of p53 and p21 protein levels and accumulation of 

senescence-associated-beta galactosidase (SA-β-gal) activity. Indeed, 

IL-1β treatment increased production of ROS, DNA damage signaling 

proteins and enhanced accumulation of γ-H2AX 

foci. ROS may function 

as intracellular messenger that modulate signaling pathways and acts 

as a critical mediator of DNA damage signaling. Furthermore,IL-1β 

treatment induced production of IL-6 which is also considered as a key 

regulator of inflammatory network in cellular senescence. Together, our 

observations support the significant role of inflammatory cytokines in 

DNA damage signaling and ROS production in mediating and 

maintaining premature cellular senescence state. 

Authors: Renuka Kandhaya -Pillai, Francesc Miro-Mur, Natalia Gracia 

Aranda, Jaume Alijotas-Reig, Simo Schwartz Jr 


53 

_________________________________________________________ 

O19-DOI: 


Mutations in PYCR1 Cause Cutis Laxa with Progeroid Features due 

to Reduced Mitochondrial Stress Resistance 

Autosomal recessive cutis laxa (ARCL) describes a group of syndromal 

progeroid disorders characterized by lax and wrinkled skin, osteopenia, 

and variable CNS involvement. Homozygosity mapping in several 

kindreds with ARCL identified a candidate region on chromosome 

17q25. By high-throuput sequencing of the entire candidate region we 

detected disease-causing mutations in the gene PYCR1 encoding 

pyrroline-5-carboxylate reductase, an enzyme involved in proline 

biosynthesis. Serum proline levels were not significantly reduced in 

patients. All mutations entailed reduction of protein expression to a 

variable degree. We found that the gene product localizes to 

mitochondria. Altered mitochondrial morphology, membrane potential 

and increased apoptosis rate upon oxidative stress were evident in 

patient fibroblasts. Knockdown of the orthologous gene and a highly 

identical paralog in zebrafish led to epidermal abnormalities that were 

accompanied by a massive increase of apoptosis. Thus, local 

production of proline in mitochondria seems to be important for cellular 

stress resistance, especially in connective tissues, resulting in 

premature cell loss and progeroid changes. 

Reversade B*, Escande-Beillard N*, Dimopoulou A, Fischer B, Chng 

SC, Li Y, Shboul M, Tham PY, Kayserili H, Al-Gazali L, Shahwan M, 

Brancati F, Lee H, O'Connor BD, Schmidt-von Kegler M, Merriman B, 

Nelson SF, Masri A, Alkazaleh F, Guerra D, Ferrari P, Nanda A, Rajab A, 

Markie D, Gray M, Nelson J, Grix A, Sommer A, Savarirayan R, 

Janecke AR, Steichen E, Sillence D, Hausser I, Budde B, Nurnberg G, 

Nurnberg P, Seemann P, Kunkel D, Zambruno G, Dallapiccola B, 

Schuelke M, Robertson S, Hamamy H, Wollnik B, Van Maldergem L, 

Mundlos S and Kornak U. Mutations in PYCR1 cause cutis laxa with 

progeroid features. Nat Genet 2009, 41, (9), 1016-21. 

Authors: Björn Fischer, Aikaterini Dimopoulou, Bruno Reversade, 

Nathalie Escande-Beillard, Yun Li, Hülya Kayserili, Francesco Brancati, 

Mareen Schmidt-von Kegler, Hane Lee, Petra Seemann, Peter 

Nürnberg, Bruno Dallpiccola, Markus Schülke, Bernd Wollnik, Stephen 

Robertson, Lionel Van Maldergem, Stefan Mundlos, Uwe Kornak, 

_________________________________________________________ 

O20- 


Mitochondrial redox regulation 

The intracellular redox milieu is of crucial importance for cellular 

homeostasis. It can influence numerous cellular processes like oxidative 

protein folding, apoptosis and respiration. Moreover, it also serves as a 

buffer towards a variety of redox stresses. For this reason, aberrant 

changes of the redox environment are often linked to human disorders 

like cancer and neurodegenerative diseases. Importantly, the 

mechanisms and dynamics underlying the regulation of the redox milieu 

are still far from being understood. We are interested in the regulation of 

the redox environment in mitochondria, i.e. in the intermembrane space 

(IMS) and the matrix. In these subcompartments as well as in the 

cytosol we can accurately monitor the redox milieu by assessing its 

main determinant: the composition of the glutathione redox buffer. To 

this end we use specifically targeted fluorescence redox sensors. From 

our findings we will deduce a model for the interplay of different redox 

pathways in the homeostasis and dynamics of the redox milieu in the 

IMS. 

Authors: Kerstin Kojer, Johannes Herrmann, Jan Riemer

_________________________________________________________ 

O21-DOI: 


Disruption of the GH-STAT5-IGF-1 axis causes hepatic fibrosis in 

the mdr2-/- mouse model of cholestasic liver disease 

Liver fibrosis constitutes a considerable health problem in the human 

population. In order to further understand the molecular mechanisms 

underlying liver fibrogenesis it is mandatory to generate genetic mouse 

models closely resembling human disease development and progression. 

Growth Hormone (GH) resistance and low serum levels of insulin-like growth 

factor 1 (IGF-1) are common features of degenerative human liver disease 

such as fibrosis and cirrhosis. GH leads to activation of hepatic Signal 

transducer and activator of transcription 5 (STAT5) which in turn controls 

several vital functions in the liver, including transcription of IGF-1, expression 

of detoxifying Cyp450 isoforms and repression of de novo lipogenesis. To 

study the role of hepatic STAT5, we specifically deleted STAT5a and STAT5b 

using Alfp-cre-mediated homologous recombination. Mice deficient for 

hepatic Stat5 (STAT5Δhep) harbored a blunted GH-STAT5-IGF-1 signaling 

axis, reflected by impaired expression of IGF-1 mRNA and protein and 

elevated GH serum titers as a secondary consequence of impaired IGF-1 

negative feedback signaling in the pituitary. Thus, STAT5Δhep animals 

encompassed major hallmarks of GH resistance. 

To investigate the role of GH resistance in liver fibrogenesis, we crossed 

STAT5Δhep animals with mice deficient for the multidrug resistance gene 2 

(Mdr2-/-), a mouse model for cholestatic liver disease. STAT5Δhep/mdr2-/ compound knockout mice developed severe liver fibrosis, jaundice, 

intrahepatic cholestasis and a perturbation of key regulators of bile acid 

homeostasis already at 3-8 weeks of age. Fibrotic animals exhibited massive 

collagen deposition in hepatic tissues, potent bile duct proliferation and a 

profound disruption of the normal liver architecture, leading to advanced 

“bridging liver fibrosis” at young age. Molecularly, we observed a reduced 

expression of important hepatoprotective genes, such as epidermal growth 

factor receptor (Egfr), hepatocyte nuclear factor-6 (Hnf6), prolactin receptor 

(Prlr) and leukemia inhibitory factor receptor (Lifr) and increased numbers of 

apoptotic hepatocytes. Further, Stat5ab-deficient hepatocytes undergo bileacid 

induced apoptosis in vitro, whereas recombinant IGF-1 administration 

prevented cell death. 

Conclusion: Our data suggest that loss of STAT5 and development of GH 

resistance sensitizes hepatocytes to bile acid-induced damage and 

apoptosis due to impairment of GH-induced transcription of IGF-1 and 

downregulation of hepatoprotective genes. 

Authors: Jan-Wilhelm Kornfeld, Leander Blaas, Monica Musteanu, 

Daniel Schramek, Gernot Zollner, Judith Gumbold, Franziska van Zijl, 

Doris Schneller, Harald Esterbauer, Gerda Egger, Markus Mair, Lukas 

Kenner, Wolfgang Mikulits, Robert Eferl, Richard Moriggl, Josef 

Penninger, Michael Trauner, Emilio Casanova 

_________________________________________________________ 

O22-DOI: 


Cathepsin X-deficient fibroblasts undergo accelerated cellular 

senescence 

Lysosomal cysteine-type peptidases (cathepsins) are highly 

upregulated in many cancers. These enymes are not confined to 

lysosomes but may also be secreted by cancer cells, and are believed 

to promote invasion/migration processes mainly by degrading 

extracellular matrix (ECM). This holds true for cathepsins B and L, 

which are able to act endoproteolytically on substrates. Surprisingly, 

also cathepsin X, a carboxypeptidase unable to hydrolyze ECM 

components, has been shown to participate in invasive processes. 

To investigate the mechanisms leading to altered invasion/migration of 

cathepsin X-deficient cells, we have analyzed mouse embryonic 

fibroblasts derived from cathepsin X-/- mice and normal human dermal 

fibroblasts transiently transfected with siRNAs targeting cathepsin X. 

Remarkably, these cells exhibit a flattened and enlarged morphology as 

well as an upregulation of several senescence-associated genes. In 

addition, cathepsin X deficiency leads to an impaired cell proliferation, 

but without a major cell cycle arrest. Instead, BrdU pulse-chase 

experiments revealed that the synthesis rate of cells lacking cathepsin X 

is markedly reduced. 

In conclusion, we demonstrated that cathepsin X deficiency leads to an 

accelerated cellular senescence phenotype and retards the synthesis 

rate during the cell cycle. Due to the high expression of this protease in 

certain tumors, it may promote tumor progression through its influence 

on invasive and/or proliferative processes. 

Authors: Steffen Kraus, Thomas Reinheckel, Marianne Jochum, Dorit 

Nägler 


54 

_________________________________________________________ 

O23-DOI: 


Novel role of the centrosomal protein TACC3 in nuclear pore 

complex assembly 

Centrosomal transforming acidic coiled-coil (TACC) domain-containing 

proteins are central players in structures and processes connected to 

the mitotic spindle apparatus. Among the three mammalian TACC 

isoforms TACC3 is expressed only during the late S/G2/M phases of the 

cell cycle where it shows a perinuclear localization before nuclear 

envelope breakdown. Interestingly, using subcellular fractionation, 

TACC3 co-purifies with lamin A, a structural component of the inner 

nuclear lamina, and TACC3 deficiency causes morphological alterations 

of the nuclear envelope possible influencing nuclear pore architecture 

[1]. To address the nature of these defects in more detail, we analyzed 

the expression and subcellular localization of several nuclear pore 

complex proteins (NUP) depending on TACC3 function. Interestingly, 

NUP62 and TACC3 colocalized during mitosis at centrosomes and 

postmitotically at the nuclear envelope of several cell lines tested. 

Concomitantly, TACC3 deficiency or shRNA-mediated TACC3 depletion 

had a major impact on nuclear pore complex assembly as indicated by 

strongly reduced perinuclear localization of NUP62. However, the 

expression of NUP62 and other NUP proteins including NUP133 was 

not significantly reduced when TACC3 was depleted. Consistent with 

this, TAC-1, the TACC isoform in C. elegans, interacts physically with 

components of the nuclear pore (NPP-1) and lamina (LMN-1) [2]. Thus, 

TACC3 is required for proper Nup62 localization at the nuclear 

membrane indicating that TACC3 has novel structural functions for the 

assembly and/or stability of nuclear pore complexes. Current work 

focuses on the electron microscopical and functional analysis of nuclear 

pores in the absence of TACC3 expression. 

[1] Gomez-Baldo et al. (2010). TACC3-TSC2 maintains nuclear 

envelope structure and controls cell division (2010). Cell Cycle, in press. 

[2] Boxem et al. (2008). A protein domain-based interactome network for 

C. elegans early embryogenesis. Cell, 134, 534 

Authors: Corinna Göbel, Laia Gomez-Baldo, Stephan Schmidt, 

Christian Hoffmann, K Addicks, Aris Astridines, Miguel Pujana, Roland 

Piekorz 

_________________________________________________________ 

O24- 


Cellular organization of amyloids and oxidatively damaged 

proteins in yeast 

We studied the cellular organization of amyloidogenic or oxidatively 

damaged proteins. Whereas the formation of amyloid aggregates is 

associated with several neurodegenerative diseases, the accumulation 

of oxidatively damaged proteins is a hallmark for cellular ageing. As a 

model for amyloidogenic proteins, we used a fusion of the prion forming 

domain of the [PSI+] prion with GFP, which can switch between a 

soluble conformation and an aggregating prion amyloid form. Using 

electron microscopy, we observed that the amyloid aggregates are 

initially organized in a ring or ribbon shaped bundle of long, 

uninterrupted fibrils intersecting a recently identified compartment for 

terminally aggregated proteins called IPOD (Insoluble Protein Deposit). 

After a very slow transition phase, fibrils appeared fragmented and 

organized in a single large aggregate adjacent to the IPOD. Only this 

latter arrangement corresponded to the mature transmissable prion 

state. As a model for oxidatively damaged proteins, we generated GFP 

fusions of proteins that are very sensitive to a form of oxidative damage 

called carbonylation. These fusions were soluble under standard 

conditions, but formed mostly one (or two) aggregate, often adjacent to 

prion aggregates at the IPOD, upon oxidative stress. Our further 

characterization of these two types of aggregates offers an explanation 

for where de novo prion amyloid induction might take place and how the 

prion matures. Moreover, disposal of oxidatively damaged proteins and 

amyloids at this cellular site resulted in their asymmetric partitioning 

during cell division. 

Authors: Jens Tyedmers, Harsha Garadi Suresh, Jijun Dong, Helen 

Saibil, Achilleas Frangakis, J. Michael McCaffery, Susan Lindquist

_________________________________________________________ 

O25-DOI: 


Treatment of human dermal fibroblasts by water-filtered infrared A 

irradiation 

Infrared A radiation (IRA) is a substantial part of the solar energy output 

reaching the earth surface. Therefore, exposure of human skin to IRA is 

very common. However, whether and how infrared (IR) or infrared A 

acts on human skin cells is still under debate. Recently the generation 

of reactive oxygen species by water-filtered infrared A (wIRA) irradiation 

was postulated. Clinically applied wIRA shows a spectral distribution 

similar to that of solar irradiation at the earth's surface. 

Thus it was concluded that there is a need for skin protection from both 

solar- and artificially generated infrared A irradiation. 

Here we were able to show that in human dermal fibroblasts the 

generation of reactive oxygen species (ROS) is dependent on heat 

formation by infrared A and can be reproduced by thermal exposure 

alone. On the other hand wIRA irradiation revealed no detectable effect 

if the temperature of the used cells was kept carefully constant, even if 

the applied amount of wIRA exceeded the extraterrestrial solar 

irradiance in the IR range at noontime in the tropics by a factor up to 

about 6. 

This could be demonstrated by the measurement of both ROSformation 

(using H2DCFDA) and the determination of induced protein 

oxidation. Additional experiments showed that mitochondria contributed 

significantly to ROS-production during thermal exposure of human 

dermal fibroblasts and that the major absorbance of infrared is due to 

energy absorption of cellular water. 

Authors: Tobias Jung, Annika Höhn, Helmut Piazena, Tilman Grune 

_________________________________________________________ 

O26- 


Genome-wide screen in Saccharomyces cerevisiae identifies 

autophagy, biosynthetic, and tRNA methylation genes involved in 

life span extension 

The use of simple model organisms has been instrumental to pinpoint 

the genes that function to control life span and to identify the molecular 

pathways whose role in aging is conserved from the unicellular yeast to 

mice. Yeast are particularly amenable to genetics and genomics studies 

and have been used widely as model system for aging research. Here 

we have exploited a powerful genomic tool, the yeast deletion 

collection, to perform a screen of a pool of non essential deletion 

mutants (~4800) to identify novel genes implicated in the regulation of 

yeast chronological life span. Our results show that normal life span 

depends on functional mitochondria and on the ability to degrade 

cellular components and proteins by autophagy. They also implicate a 

novel cell signaling protein (CK2) and cellular processes such as fatty 

acid metabolism, amino acid biosynthesis, tRNA modification, and 

translation in modulating yeast chronological aging. The high level of 

conservation of the novel life span regulatory genes suggests that their 

role in longevity regulation might be conserved in higher eukaryotes 

Authors: Paola Fabrizio, Shawn Hoon, Mehrnaz Shamalnasab, 

Abdulaye Galbani, Min Wei, Guri Giaever, Corey Nislow, Valter Longo 


55 

_________________________________________________________ 

O27-DOI: 


Genetic and biochemical evidence that excess levels of BCAA 

shorten Drosophila life span 

Excessive dietary protein is known to reduce lifespan while a proteinpoor, 

low calorie diet can increase life expectancy. The biochemical 

basis for this phenomenon is unknown, however. We profiled miRNA 

expression in young as well as aged fruit flies and discovered that miR- 

277 is down-regulated with age. With the help of an RNA pulse-labeling 

strategy we determined that the direct targets of miR-277 are enzymes 

involved in the degradation of branched-chain amino acids (BCAAs). To 

counteract the physiologic reduction of miR-277 with age, we generated 

transgenic flies expressing miR-277 from a strong, constitutive 

promotor. As a consequence, these flies have reduced expression 

levels of the BCAA-degrading enzymes and show a drastically reduced 

life span, particularly on food that contains a high amount of protein but 

a low amount of carbohydrates. Furthermore, food enriched with BCAAs 

leads to a reduced lifespan in wild-type flies, partially explaining the lifespan 

shortening effect of a high-protein diet. In summary, both genetic 

as well as biochemical data suggest that high levels of branched-chain 

amino acids have detrimental effects on life expectancy. 

Authors: Stephanie Esslinger, Romy Böttcher, Björn Schwalb, Achim 

Tresch, Klaus Förstemann 

_________________________________________________________ 

O28-DOI: 


Short lifetime without Ceramide synthase 3 

Skin serves a quintessential function as barrier towards our 

environment. When the epidermal barrier has broken down, pathogens 

can easily enter the skin, leading to secondary fungal (dermatophytosis) 

and bacterial infections (staphylococcus aureus). At the same time the 

water permeability barrier (WPB) in the outer layer of the epidermis 

prevents land dwelling animals from desiccation. Extracellular lipid 

lamellae between the corneocytes are an essential part of the WPB. 

These lamellae contain high concentrations of ceramides with very long 

chain (C30-C36) omega-hydroxylated fatty acid moieties. 

In vitro data suggest, that only ceramide synthase 3 (CerS3) but not 

CerS2 is capable to produce ceramides of this type. Furthermore, the 

co-expression of one (CerS3) out of six CerS and of very long chain 

sphingolipids in skin and testis suggested the involvement of CerS3 in 

the biosynthesis of omega hydroxy-ceramides in the epidermis. 

In this study, we show, that mice with a mutated ceramide synthase 3, 

lack all sphingolipids with very long chain acyl moieties. As a 

consequence 90 % of the epidermal sphingolipids are gone leading to a 

disrupted WPB in mutant mice which die shortly after birth. 

Authors: Richard Jennemann, Mariona Rabionet, Sharon Epstein, 

Walter Nickel, Howard Riezman, Karin Gorgas, Hermann-Josef Gröne, 

Roger Sandhoff

_________________________________________________________ 

O29-DOI: 


Functional Analysis of Silent Information Regulator-2 (SIR-2) 

Proteins in Caenorhabditis elegans 

Silent information regulator-2 (SIR-2) proteins are NAD+ -dependent 

protein deacetylases that are highly conserved in organisms ranging 

from bacteria to humans. In yeast SIR-2 was originally identified as a 

factor necessary for epigenetic silencing of the mating type loci, 

telomeres, and ribosomal DNA (rDNA). Since overexpression of SIR-2 

increases life span of yeast, C. elegans, and Drosophila, SIR-2 proteins 

have become intriguing players in regulating longevity and linking 

metabolism to aging and age-related diseases. The mammalian sirtuin 

protein family comprising seven members (SIRT1 to SIRT7) is quite 

complex and the biological functions, especially of the variants SIRT2- 

SIRT7, still have to be fully elucidated. Therefore, the multicellular 

organism C. elegans with only four different SIR-2 variants (sir-2.1 to 

sir-2.4) offers an excellent model system to analyze the function of 

sirtuins. Mammalian sirtuins are targeted to different subcellular 

localizations (nucleus, cytoplasm, and mitochondria), suggesting that 

they regulate metabolism, stress responses and aging-related 

processes at different subcellular levels. In addition, it remains open 

whether there is interplay between different sirtuin variants. We are 

interested in the biological function of SIR-2 proteins in the multicellular 

organism C. elegans. In particular we are analyzing the less 

characterized variants sir-2.2 and sir-2.3 and their possible role in 

regulating metabolism and stress responses. 

Authors: Martina Wirth, Dirk Wenzel, Timur Samatov, Dmitry Agafonov, 

Monika Jedrusik-Bode, Wolfgang Fischle 

_________________________________________________________ 

O30- 

late Abstract (no DOI generated) 

AN ALTERED HIPPOCAMPAL HISTONE CODE IS ASSOCIATED 

WITH AGE- DEPENDENT MEMORY IMPAIRMENT 

During aging, a marked gradual decline is frequently observed in the 

performance of cognitive and memory tasks. Importantly, aging is also 

the major risk factor for neurodegenerative diseases such as 

Alzheimer's disease (AD), which affect millions of people worldwide. 

The reasons for the decline in brain function during aging, is however 

not well understood. 

A number of recent studies including our work (Fischer et al, 2007, 

Nature, 447) suggest that epigenetic factors may play a central role in 

memory formation and age related pathologies. In addition to the role of 

transcription factors, the availability of genes for transcription is 

controlled by a series of proteins that regulate epigenetic chromatin 

remodeling, especially histone-acetyltransferases (HATs) and histonedeacetylases 

(HDACs). Particularly, the inhibition of HDACs has been 

implicated with facilitated learning ability and increased neuronal 

plasticity in rodents. 

By combining biochemical and behavioral approaches with chromatin 

immunoprecipitation followed by massive parallel sequencing (ChIP- 

Seq) we show that the onset of age-dependent de-regulation of 

hippocampal gene-expression and learning impairment is linked to a 

deficit in histone acetylation. Notably, acute treatment of aged mice with 

inhibitors of histone-deacetylases was able to partially restore 

physiological histone acetylation, gene-expression and learning ability in 

aged mice. This data shows for the first time that deregulated 

chromatin-plasticity is causally linked to age-associated memory 

impairment and that drugs that increase histone acetylation might be a 

suitable therapeutic avenue to treat age-associated memory decline. 

Authors: Shahaf Peleg, Farahnaz Sananbenesi, Athanasios Zovoilis, 

Roman Stilling, Laurent Farinelli & Andre Fischer 


56 

_________________________________________________________ 

O31-late 

Abstract (no DOI generated) 

Targeted inactivation of the mouse NOA1 gene 

atNOS1 protein was originally described by (Guo et al., 2003) in the 

plant as a putative nitric oxide synthases. Our interest in the gene was 

sparked by the realization that it belongs to a novel evolutionary 

conserved GTP-binding protein family, with members in organisms 

ranging from bacterium to human (Zemojtel et al., 2004). In search for a 

possible source of nitric oxide in osteoblasts, we identified a mammalian 

ortholog of atNOS1 protein and showed that it functions in the subcellular 

context of mitochondria (Zemojtel et al., 2006b). In spite of 

intensive effort in our and several other laboratories nitric oxide 

synthase activity of atNOS1 in-vitro could not be confirmed. Based on 

biochemical and bioinformatic data we proposed that atNOS1 (now 

termed /Noa1/ - Nitric Oxide Associated1) contributes to cellular NO 

production indirectly, by the control of mitochondrial ribosome assembly 

and/or process of translation (Zemojtel et al., 2006a). In order to 

experimentally address /N//oa//1/ function we aim at generation of the 

NOA1 knock-out mice. Here we present strategy for NOA1 gene 

inactivation and preliminary data on the gene targeting in the ES cells. 

Guo, F. Q., Okamoto, M., and Crawford, N. M. (2003). Identification of a 

plant nitric oxide synthase gene involved in hormonal signaling. 

Science/ 302/, 100-103. 

Zemojtel, T., Frohlich, A., Palmieri, M. C., Kolanczyk, M., Mikula, I., 

Wyrwicz, L. S., Wanker, E. E., Mundlos, S., Vingron, M., Martasek, P., 

and Durner, J. (2006a). Plant nitric oxide synthase: a never-ending 

story? Trends Plant Sci/ 11/, 524-525; author reply 526-528. 

Zemojtel, T.and Kolanczyk, M., Kossler, N., Stricker, S., Lurz, R., Mikula, 

I., Duchniewicz, M., Schuelke, M., Ghafourifar, P., Martasek, P./, et al./ 

(2006b). Mammalian mitochondrial nitric oxide synthase: 

characterization of a novel candidate. FEBS Lett/ 580/, 455-462. 

Zemojtel, T., Penzkofer, T., Dandekar, T., and Schultz, J. (2004). A novel 

conserved family of nitric oxide synthase? Trends Biochem Sci/ 29/, 

224-226. 

Authors: Mateusz Kolanczyk

List of Participants (in alphabetical order) 

name city, country 

email 

Aguilaniu, Hugo Lyon, FR hugo.aguilaniu@ens-lyon.fr 

Alves, Juergen Hannover, DE alves.juergen@mh-hannover.de 

Angerer, Heike Frankfurt am Main, DE angerer@zbc.kgu.de 

Antebi, Adam Koeln, DE aantebi@age.mpg.de 

Apel, Tino Frankfurt am Main, DE apel@gbm-online.de 

Aphkhazava, David Berlin, DE abchasava@yahoo.com 

Asrat, Silvia Köln, DE silvia.asrat@uk-koeln.de 

Assfalg, Robin Ulm, DE robin.assfalg@uni-ulm.de 

Auburger, Georg Oberursel, DE auburger@em.uni-frankfurt.de 

Bartelt, Alexander Hamburg, DE abartelt@uke.uni-hamburg.de 

Barth, Christian München, DE mailing@gbm-online.de 

Bartke, Andrzej Springfield, US abartke@siumed.edu 

Baumann, Bernd Ulm, DE bernd.baumann@uni-ulm.de 

Baumgart, Mario Jena, DE mbaumgart@fli-leibniz.de 

Beher, Dirk Geneva, CH dirk.beher@merckserono.net 

Behrendt, Marc Salzhemmendorf, DE bemarc@web.de 

Belgardt, Bengt Köln, DE bengt.belgardt@uni-koeln.de 

Benzing, Thomas Cologne, DE thomas.benzing@uk-koeln.de 

Bernd, August Frankfurt/M, DE bernd@em.uni-frankfurt.de 

Bleier, Lea Frankfurt, DE bleier@zbc.kgu.de 

Bobrich, Manuel Giessen, DE manuel.bobrich@anatomie.med.uni-giessen.de 

Böckemeier, Lennart Göttingen, DE L.Boeckemeier@stud.uni-goettingen.de 

Brandt, Ulrich Frankfurt, DE brandt@zbc.kgu.de 

Bratic, Ivana Koeln, DE ivana.bratic@uk-koeln.de 

Braun, Manfred Frankfurt, DE braun@gbm-online.de 

Brendel, Alexander Mainz, DE brendela@uni-mainz.de 

Breunig, Karin Halle/Saale, DE karin.breunig@genetik.uni-halle.de 

Brobeil, Alexander Geislingen, DE alexander.brobeil@anatomie.med.uni-giessen.de 

Brodesser, Susanne Cologne, DE susanne.brodesser@uk-koeln.de 

Brüning, Jens Köln, DE jens.bruening@uni-koeln.de 

Bunse, Carola Bocholt, DE carola.bunse@freenet.de 

Buschow, Rene Berlin, DE buschow@molgen.mpg.de 

Calkhoven, Cornelis Jena, DE calkhoven@fli-leibniz.de 

Campisi, Judith Berkeley, US jcampisi@lbl.gov 

Canlon, Barbara Stockholm , SE barbara.canlon@ki.se 

Charvin, Gilles Lyon, FR gilles.charvin@gmail.com 

Christ, Bruno Halle, DE bruno.christ@medizin.uni-halle.de 

Dawson, Ted Baltimore, US tdawson@jhmi.edu 

de Haan, Gerald Groningen, NL g.de.haan@med.umcg.nl 

Dencher, Norbert A. Darmstadt, DE norbert.dencher@physbiochem.tu-darmstadt.de 

Deuerling, Elke Konstanz, DE elke.deuerling@uni-konstanz.de 

Dexheimer, Verena Heidelberg, DE verena.dexheimer@med.uni-heidelberg.de 

Dick, Niko Bonn, DE ndick@uni-bonn.de 

Dillin, Andrew La Jolla, US info@gbm-online.de 

Ding, Martina Frankfurt, DE Ding@zbc.kgu.de 

Dingler, Felix Stuttgart, DE felix.dingler@web.de 

Doenecke, Detlef Göttingen, DE ddoenec@gwdg.de 

Dogan, Sukru Anil Cologne, DE sukru.dogan@uk-koeln.de 

Dreiseidler, Michael Bonn, DE dreiseidler@uni-bonn.de 

Dringen, Ralf Bremen, DE ralf.dringen@uni-bremen.de 

Dröse, Stefan Frankfurt am Main, DE droese@zbc.kgu.de 

Drost, Jessica Frankfurt am Main, DE J.Drost@med.uni-frankfurt.de 

Dunkelmann, Tina Rostock, DE tina.dunkelmann@uni-rostock.de 

Eberhardt, Martin Erlangen, DE martin.eberhardt@biochem.uni-erlangen.de 

Egerer, Johannes Berlin, DE johannes.egerer@charite.de 

Egge, Heinz Bonn, DE hegge@uni-bonn.de 

Eichler, Wolfgang Recklinghausen, DE wolfgang.eichler@lanuv.nrw.de 

Eissing, Leah Hamburg, DE leissing@uke.uni-hamburg.de 

El Magraoui, Fouzi Bochum, DE Fouzi.ElMagraoui@rub.de 

Ermolaeva, Maria Koeln, DE ermolaem@uni-koeln.de 

57


name city, country email 

Fabian, jenny Rostock, DE jenny.fabian@uni-rostock.de 

Fabretti, Francesca Köln, DE francesca.fabretti@uk-koeln.de 

Fabrizio, Paola Lyon, FR fabrizio@usc.edu 

Feldmann, Heidi München, DE fmann@lmb.uni-muenchen.de 

Ferchiu, Ionela-Florentina Ulm, DE florentina.ferchiu@uni-ulm.de 

Fischer, Andre Göttingen, DE afische2@gwdg.de 

Fischer, Björn Berlin, DE fischer_bjoern@gmx.de 

Fischer, Sebastian Hannover, DE fisseb4@gmx.de 

Fleck, Daniel München, DE DanielFleck@web.de 

Follmann, Hartmut Marburg, DE follmann-marburg@t-online.de 

Förstemann, Klaus München, DE Foerstemann@lmb.uni-muenchen.de 

Franke, Jacqueline Berlin, DE jacqueline.franke@htw-berlin.de 

Frenzel, Monika Darmstadt, DE monika.frenzel@web.de 

Freude, Susanna Koeln, DE susanna.freude@uk-koeln.de 

Frieland, Rainer Heidelberg, DE r.frieland@online.de 

Friemel, Martin Berlin, DE M.Friemel@t-online.de 

Fröhlich, Christina Rostock, DE cf131@uni-rostock.de 

Fuellen, Georg Rostock, DE fuellen@uni-rostock.de 

Gast, Daniela Tübingen, DE daniela.gast@rpt.bwl.de 

Gaunitz, Frank Leipzig, DE fgau@medizin.uni-leipzig.de 

Geiger, Hartmut Ulm, DE hartmut.geiger@uni-ulm.de 

Gerlach, Claudia Jena, DE claudia.gerlach@mti.uni-jena.de 

Gey, Claudia Lübeck, DE gey@uni-luebeck.de 

Göbel, Corinna Düsseldorf, DE Corinna.Goebel@uni-duesseldorf.de 

Goldmann, Jakob Göttingen, DE jakob.goldmann@freenet.de 

Grathwohl, Stefan Tübingen, DE s.grathwohl@gmx.de 

Grether-Beck, Susanne Düsseldorf, DE Grether-Beck@uni-duesseldorf.de 

Grünz, Gregor Freising, DE gruenz@wzw.tum.de 

Guarente, Leonard P. Cambridge, US leng@mit.edu, (Assistent: ovieira@mit.edu) 

Gülow, Karsten Heidelberg, DE k.guelow@dkfz.de 

Hahn, Uli Hamburg, DE uli.hahn@uni-hamburg.de 

Hajieva, Parvana Mainz, DE hajieva@uni-mainz.de 

Hamprecht, Bernd Tübingen, DE bernd.hamprecht@uni-tuebingen.de 

Harmel, Julia Köln, DE Julia.Harmel@age.mpg.de 

Hartmann, Nils Jena, DE hartmann@fli-leibniz.de 

Haussmann, Hans-Juergen Roesrath, DE hansj.haussmann@t-online.de 

Heestand, Bree Houston, US heestand@bcm.edu 

Helenius, Ari Zürich, CH ari.helenius@bc.biol.ethz.ch 

Hensel, Niko Hannover, DE n-hensel@web.de 

Herrlich, Peter Jena, DE pherrlich@fli-leibniz.de 

Herrmann, Johannes Kaiserslautern, DE hannes.herrmann@biologie.uni-kl.de 

Heumann, Rolf Bochum, DE rolf.heumann@rub.de 

Heyne, Kristina Homburg-Saar, DE kristinaheyne@aol.com 

Hilf, Ricarda Portland, US ricardahilf@gmx.net 

Hirschmann, Wolf Steinheim, DE wolf.hirschmann@online.de 

Hoeijmakers, Jan H. J. Rotterdam, NL j.hoeijmakers@erasmusmc.nl 

Hoercher, Renate Penzberg, DE renate.hoercher@roche.com 

Hoffmann, Gesine Essen, DE gesine.hoffmann@uni-due.de 

Hoffmann, Julia Kiel, DE jhoffmann@zoologie.uni-kiel.de 

Höhfeld, Jörg Bonn, DE hoehfeld@uni-bonn.de 

Höhn, Annika Stuttgart, DE ahoehn@uni-hohenheim.de 

Holl, Daniel Bonn, DE dholl@uni-bonn.de 

Holloszy, John Saint Louis, US jhollosz@dom.wustl.edu 

Holtkötter, Olaf Düsseldorf, DE olaf.holtkoetter@henkel.com 

Holz, Gabriele Frankfurt am Main, DE holz@gbm-online.de 

Honnen, Sebastian Duisburg, DE sjhonnen@googlemail.com 

Hopf, Carsten Mannheim, DE c.hopf@hs-mannheim.de 

Hörold, Kristina Gießen, DE hoerold_kristina@web.de 

Horstkorte, Rüdiger Halle (Saale), DE ruediger.horstkorte@medizin.uni-halle.de 

Huebner, Guenter Freital, DE guenter.huebner.gh@web.de 

58



Hupfer, Stephan Erlangen, DE stephan.hupfer@biochem.uni-erlangen.de 

Iben, sebastian Ulm, DE sebastian.iben@uni-ulm.de 

Irmgard, Sinning Heidelberg, DE irmi.sinning@bzh.uni-heidelberg.de 

Jacob, Wright Bochum, DE towjacobmg@yahoo.com 

Jansen, Ralf-Peter Tübingen, DE ralf.jansen@uni-tuebingen.de 

Jedrusik-Bode, Monika Göttingen, DE mjedrus@gwdg.de 

Jenkins, Gail Sharnbrook, Bedford, GB gail.jenkins@unilever.com 

Jerrentrup, Caroline Hannover, DE c.jerrentrup@gmx.de 

Junemann, Alexander Hannover, DE alex.june@gmx.de 

Jung, Tobias Stuttgart, DE tobias.jung@uni-hohenheim.de 

Kadowaki, Takashi Tokyo, JP kadowaki-3im@h.u-tokyo.ac.jp 

Kaeberlein, Matt Seattle, US kaeber@u.washington.edu 

Kahl, Günter Frankfurt am Main, DE kahl@em.uni-frankfurt.de 

Kaminski, Marcin Heidelberg, DE m.kaminski@dkfz.de 

Kandhaya Pillai, Renuka Barcelona, ES renugene@gmail.com 

Kemmerling, Björn Marburg, DE Kemmerli@students.uni-marburg.de 

Kenyon, Cynthia San Francisco, US Cynthia.Kenyon@ucsf.edu kenyon.cynthia@gmail.com 

Kern, Andreas Mainz, DE akern@uni-mainz.de 

Kevei, Eva Köln, DE keveie@uni-koeln.de 

Kiltz, Hans-Hermann Bochum, DE hans-hermann.kiltz@ruhr-uni-bochum.de 

Klement, Karolin Jena, DE kklement@fli-leibniz.de 

Kloeckener, Tim Cologne, DE Tim.Kloeckener@uni-koeln.de 

Klofat, Walther Bonn, DE 

Klöppel, Christine Kaiserslautern, DE tina.kloeppel@biologie.uni-kl.de 

Klug, Wilfried Heidelberg, DE wklug@gmx.net 

Koch, Ina Berlin, DE ina.koch@molgen.mpg.de 

Kojer, Kerstin Kaiserslautern, DE kerstin.kojer@biologie.uni-kl.de 

Kolanczyk, Mateusz Berlin, DE kolanshy@molgen.mpg.de 

Koob, Sebastian Darmstadt, DE koob@zbc.kgu.de 

Kornak, Uwe Berlin, DE uwe.kornak@charite.de 

Kornfeld, Jan-Wilhelm Köln, DE jkornfel@uni-koeln.de 

Kraemer, Reinhard Juelich, DE r.kraemer@uni-koeln.de 

Kraus, Steffen München, DE steffen.kraus@med.uni-muenchen.de 

Krebs, Joachim Forch, CH jkrebs@nmr.mpibpc.mpg.de 

Küper, Thomas Holzminden, DE Thomas.Kueper@symrise.com 

Kukat, Alexandra Köln, DE alexandra.kukat@uk-koeln.de 

Kukat, Christian Köln, DE christian.kukat@age.mpg.de 

Kumar, Manish Bad Nauheim, DE manish.kumar@mpi-bn.mpg.de 

Kurshid, Safiya Koeln, DE safiya.kurshid@uk-koeln.de 

Kurz, Alexander Frankfurt am Main, DE a.kurz@med.uni-frankfurt.de 

Lahmann, Marlen Göttingen, DE Marlen3009@freenet.de 

Lange, Friederike Rostock, DE spaghetti04@web.de 

Langer, Thomas Köln, DE thomas.langer@uni-koeln.de 

Larsson, Nils-Göran Stockholm, SE Nils-Goran.Larsson@ki.se 

Lichtenberg, Ursula Köln, DE u.lichtenberg@uni-koeln.de 

Lill, Roland Marburg, DE Lill@staff.uni-marburg.de 

Loeffler, Monika Marburg, DE loeffler@staff.uni-marburg.de 

Loerwald, Andrea Carolin Wilhelmsfeld, DE andrea.loerwald@gmx.de 

Lohöfener, Jan Hannover, DE jan-lo@web.de 

Longo, Valter D. Los Angeles, US vlongo@usc.edu 

Luke, Brian Heidelberg, DE b.luke@zmbh.uni-heidelberg.de 

Maass, Günter Hannover, DE 

Mallow, Helfried Regensburg, DE helfried.mallow@vkl.uni-regensburg.de 

Mangerich, Aswin Konstanz, DE aswin.mangerich@uni-konstanz.de 

Marsching, Christian Mannheim, DE c.marsching@hs-mannheim.de 

Marthandan, Shiva Jena, DE smarthandan@fli-leibniz.de 

Martin, Nikolas Springe, DE punk2k@web.de 

März, Annette Hamburg, DE annette.maerz@beiersdorf.com 

Mauer, Jan Köln, DE j.mauer@uni-koeln.de 

Mayer, Doris Heidelberg, DE d.mayer@dkfz.de 

59



Merkwirth, Carsten Cologne, DE aei67@uni-koeln.de 

Mesaros, Andrea Köln, DE AMesaros@age.mpg.de 

Meyer, Helmut E. Bochum, DE mailing@gbm-online.de 

Miller, Richard Ann Arbor, US millerr@umich.edu 

Mocko, Justyna Mainz, DE mocko@uni-mainz.de 

Moll, Lorna Bergheim, DE lorna.moll@uk-koeln.de 

Müller, Christine Jena, DE cmueller@fli-leibniz.de 

Müller, Isabelle Blieskastel, DE ellebasi_de@yahoo.de 

Müller, Matthias Offenbach, DE mueller@zbc.kgu.de 

Mueller, Michael Köln, DE mueller.m@uni-koeln.de 

Müller, Nathalie Konstanz, DE nathalie.mueller@uni-konstanz.de 

Müller, Roman-Ulrich Köln, DE roman-ulrich.mueller@uk-koeln.de 

Muench, Sandra Jena, DE smuench@fli-leibniz.de 

Muster, Britta Frankfurt am Main, DE b.muster@med.uni-frankfurt.de 

Neubauer, Robert Frankfurt am Main, DE robert.neubauer@yahoo.de 

Neuhaus, Brit Köln, DE Brit.Neuhaus@age.mpg.de 

Neumann, Sebastian Bochum, DE Sebastian.Neumann@ruhr-uni-bochum.de 

Nübel, Esther Frankfurt, DE nuebel@zbc.kgu.de 

Nystrom, Thomas Gothenburg, SE thomas.nystrom@cmb.gu.se 

Paarmann, Kristin Rostock, DE Kristin_Paarmann@web.de 

Peleg, Shahaf Goettingen, DE speleg@gwdg.de 

Penninger, Josef M. Wien, AT Josef.Penninger@imp.ac.at 

Pfanner, Nikolaus Freiburg, DE Nikolaus.Pfanner@biochemie.uni-freiburg.de 

Piekorz, Roland Düsseldorf, DE Roland.Piekorz@uni-duesseldorf.de 

Pipercevic, Joka München, DE joka8joka8@yahoo.de 

Planz, Jutta Gießen, DE jutta.planz@gmail.com 

Pluskota, Adam Düsseldorf, DE Adam.Pluskota@uni-duesseldorf.de 

Pohlmann, Regina Muenster, DE rpohlma@uni-muenster.de 

Popilka, Leonhard München, DE leonhardpopilka@gmx.de 

Pujol, Claire Cologne, DE claire.pujol@uk-koeln.de 

Raffler, Nikolai Bonn, DE nikolai.raffler@dfg.de 

Rastedt, Wiebke Hannover, DE wiebke.rastedt@googlemail.com 

Reichert, Andreas Frankfurt, DE reichert@zbc.kgu.de 

Reichert, Olga Hannover, DE ola-reichert@web.de 

Reichrath, Sandra Saarbrücken, DE sanhess@hotmail.com 

Reininghaus, wolf Köln, DE wolf@reininghaus.name 

Reiser, Georg Magdeburg, DE georg.reiser@med.ovgu.de 

Riedel, Marlis Hamburg, DE Marlis.Riedel@Beiersdorf.com 

Riemer, Jan Kaiserslautern, DE jan.riemer@biologie.uni-kl.de 

Ristow, Michael Jena, DE mristow@mristow.org 

Robra, Lena Barsinghausen, DE Lena_robra@gmx.de 

Rödiger, Julia Jena, DE julia.roediger@mti.uni-jena.de 

Roell, Daniela Jena, DE daniela.roell@mti.uni-jena.de 

Roemer, Klaus Homburg (Saar), DE klaus.roemer@uks.eu 

Romey, Renja Kiel, DE rromey@zoologie.uni-kiel.de 

Rössler, Oliver G. Homburg/Saar, DE bcoroe@uks.eu 

Röth, Daniel Heidelberg, DE danielroeth@gmx.de 

Rudolph, K. Lenhard Ulm, DE lenhard.rudolph@uni-ulm.de 

Saathoff, Matthias Holzminden, DE m.saathoff@hamburg.de 

Sandhoff, Konrad Alfter, DE sandhoff@uni-bonn.de 

Sandhoff, Roger Heidelberg, DE r.sandhoff@dkfz.de 

Sass, Sabine Heidelberg, DE s.sass@dkfz.de 

Schäfer, Eva Darmstadt, DE eva.r.schaefer@physbiochem.tu-darmstadt.de 

Scharffetter-Kochanek, Karin Ulm, DE karin.scharffetter-kochanek@uniklinik-ulm.de 

Schauer, Roland Kiel, DE schauer@biochem.uni-kiel.de 

Schauerte, Celina Hannover, DE Celina.Schauerte@web.de 

Schermer, Bernhard Brühl, DE bernhard.schermer@uk-koeln.de 

Schiele, Ulrich Riemerling, DE UlrichSchiele@gmx.de 

Schilbach, Katharina Köln, DE katharina.schilbach@uk-koeln.de 

Schindeldecker, Mario Mainz, DE mario.schindeldecker@googlemail.com 

60



Schippers, Christopher Cologne, DE c.schippers@uni-koeln.de 

Schlotte, Susanne Jena, DE Susanne.Schlotte@uni-jena.de 

Schmeisser, Sebastian Jena, DE sebastian.schmeisser@uni-jena.de 

Schmid, Heide Reutligen, DE schmid.heide@t-online.de 

Schmidt, Lena Frankfurt am Main, DE schmidt@zbc.kgu.de 

Schmidt, Marion Bronx, US marion.schmidt@einstein.yu.edu 

Schmidt, Stephan Düsseldorf, DE Stephan-Schmidt@uni-duesseldorf.de 

Schmidt-Straßburger, Uta Ulm, DE uta.schmidt-strassburger@uni-ulm.de 

Schmitz, Brigitte Bonn, DE schmitz@uni-bonn.de 

Schmoll, Dieter Frankfurt, DE dieter.schmoll@sanofi-aventis.com 

Schneider, Toni Köln, DE toni.schneider@uni-koeln.de 

Schopohl, Patrick Marburg, DE patrick.schopohl@gmail.com 

Schreiber, Christine Heidelberg, DE biospektrum@springer.com 

Schröder, Werner Wuppertal, DE werner.schroeder@bayerhealthcare.com 

Schroeder, Peter Duesseldorf, DE schroedp@uni-duesseldorf.de 

Schrötter, Andreas Bochum, DE Andreas.Schroetter@rub.de 

Schubert, Markus Koeln, DE markus.schubert@uni-koeln.de 

Schulz, Wolfgang Düsseldorf, DE wolfgang.schulz@uni-duesseldorf.de 

Schweizer, Ulrich Berlin, DE ulrich.schweizer@charite.de 

Seckler, Robert Potsdam-Golm, DE seckler@uni-potsdam.de 

Sesterhenn, Fabian Gundelfingen/Freiburg, DE fabian.sesterhenn@web.de 

Shamalnasab, Mehrnaz Lyon, FR mehrnaz.shamalnasab@ens-lyon.fr 

Sies, Helmut Düsseldorf, DE sies@uni-duesseldorf.de 

Simm, Andreas Halle, DE andreas.simm@medizin.uni-halle.de 

Singer, Anja Lena Düsseldorf, DE l.singer@uni-duesseldorf.de 

Spanier, Britta Freising, DE spanier@wzw.tum.de 

Steckelberg, Anna-Lena Cologne, DE lena.steckelberg@web.de 

Steegborn, Clemens Bayreuth, DE Clemens.Steegborn@rub.de 

Stephan, Jessica Essen, DE jessica.stephan@uni-due.de 

Stiller, Barbara Cologne, DE barbara.stiller@uk-koeln.de 

Stilling, Roman Göttingen, DE roman.stilling@googlemail.com 

Stoffel, Wilhelm Köln, DE wilhelm.stoffel@uni-koeln.de 

Stöhr, Oliver Köln, DE oliver.stoehr@uk-koeln.de 

Strecker, Valentina Frankfurt, DE Strecker@zbc.kgu.de 

Stühler, Kai Bochum, DE kai.stuehler@rub.de 

Tain, Luke Koeln, DE ltain@age.mpg.de 

Tanzi, Rudolph Charlestown, US tanzi@helix.mgh.harvard.edu 

Tappe, Kim Hannover, DE kim.tappe@hotmail.de 

Thiel, Gerald Homburg, DE gerald.thiel@uks.eu 

Thiel, Nadine Hannover, DE thiel.nadine@arcor.de 

Thierbach, René Hannover, DE r.thierbach@gmx.de 

Thilmany, Sandra Darmstadt, DE sandra.thilmany@physbiochem.tu-darmstadt.de 

Trifunovic, Aleksandra Köln, DE aleksandra.trifunovic@uk-koeln.de 

Trojahn, Carina Marburg, DE carina_trojahn@gmx.de 

Trommer, Wolfgang E. Kaiserslautern, DE trommer@chemie.uni-kl.de 

Tyedmers, Jens Heidelberg, DE j.tyedmers@zmbh.uni-heidelberg.de 

Ucar, Melek Emine Koeln, DE ucarm@uni-koeln.de 

Ulrich, Saskia Hannover, DE Saskia.Ulrich@gmx.net 

van Heemst, Diana Leiden, NL d.van_heemst@lumc.nl 

Van Remmen, Holly San Antonio, US vanremmen@uthscsa.edu 

Vas, Virag Ulm, DE virag.vas@uni-ulm.de 

Vora, Mehul New Brunswick, US mehulmvora@gmail.com 

Vorwerk, Hanne Hannover, DE hanne.vorwerk@web.de 

Waldera, Daniel Bochum, DE daniel.waldera@rub.de 

Wallace, Douglas C. Irvine, US mammag@uci.edu 

Walter, Michael Berlin, DE m.walter@charite.de 

Weidemann, Marina Isenbüttel, DE marina.weidemann@web.de 

Weiher, Hans Rheinbach, DE hans.weiher@fh-brs.de 

Weiss, Heike Rostock, DE Heike.Weiss@med.uni-rostock.de 

Wenz, Tina Cologne, DE tiwenz@yahoo.de 

61



Werner, Andreas Newcastle, GB andreas.werner@ncl.ac.uk 

Werner, Christian Homburg, DE christian.werner@uks.eu 

Werner, Jennifer Köln, DE jwerner@age.mpg.de 

Westermann, Benedikt Bayreuth, DE benedikt.westermann@uni-bayreuth.de 

Wienen, Barbara Marburg, DE BarbaraWienen@web.de 

Wiesner, Rudolf Köln, DE rudolf.wiesner@uni-koeln.de 

Wild, Klemens Heidelberg, DE klemens.wild@bzh.uni-heidelberg.de 

Willmes, Diana Cologne, DE diana.willmes@uni-koeln.de 

Wimmer, Monika Giessen, DE Monika.Wimmer@anatomie.med.uni-giessen.de 

Winterhoff, Moritz Hannover, DE moritz.winterhoff@gmx.de 

Wirth, Martina Göttingen, DE mwirth@gwdg.de 

Wittig, Ilka Frankfurt, DE wittig@zbc.kgu.de 

Wittinghofer, Alfred Dortmund, DE alfred.wittinghofer@mpi-dortmund.mpg.de 

Wlaschek, Meinhard Ulm, DE Meinhard.Wlaschek@uni-ulm.de 

Wolfes, Heiner Hannover, DE wolfes.heiner@mh-hannover.de 

Wumaier, Zibiernisha Frankfurt am Main, DE wumaier@zbc.kgu.de 

Wunderlich, F. Thomas Cologne, DE Thomas.wunderlich@uni-koeln.de 

Xiang, Wei Erlangen, DE wei.xiang@biochem.uni-erlangen.de 

Zarse, Kim Jena, DE kim.zarse@uni-jena.de 

Zemva, Johanna Köln, DE johanna_zemva@hotmail.com 

Zickermann, Volker Schöneck, DE Zickermann@zbc.kgu.de 

Ziehm, Matthias Cambridge, GB matthias.ziehm@ebi.ac.uk 

Zondag, Gerben Leiden, NL g.zondag@dnage.nl 

Zuschratter, Werner Magdeburg, DE zuschratter@ifn-magdeburg.de 

62

Notes 

63

61. Mosbacher Kolloquium 

A meeting of the German Society for 

Biochemistry and Molecular Biology (GBM)

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