PROGRAM & ABSTRACTS - Wisconsin Union - University of ...

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Aging, Metabolism, Stress, Pathogenesis, and Small RNAs in C. elegans Topic Meeting 2012 Pathways that regulate Reproductive Aging and Longevity Coleen Murphy Princeton University, Princeton, NJ, United States The understanding of the regulation of early aging is likely to be particularly helpful in improving quality of life. To that end, we study not only life span, but also such early aging phenotypes as loss of reproductive capacity. While the daf-2 Insulin/IGF-1-like signaling pathway and daf-16/FoxO are critical regulators of both of these phenotypes, other factors are emerging as regulators of specific aspects of aging. For example, TGF-beta dauer signaling affects longevity, but not reproductive span, while TGF-beta Sma/Mab signaling regulates reproductive aging but not longevity. Both autonomous and non-autonomous activities play a role in regulating and coordinating these pathways’ regulation of their transcriptional targets as well as their final phenotypic outputs. Contact: ctmurphy@princeton.edu Lab: Murphy 20 Session 3 Plenary Speaker
Contact: dpark@cmmt.ubc.ca Lab: Taubert Aging, Metabolism, Stress, Pathogenesis, and Small RNAs in C. elegans Topic Meeting 2012 A Novel Role of TGF-β Pathway in Dietary Restriction Induced Longevity Donha Park 1,2 , Dara Lo 1 , Charles Yang 1 , Donald Riddle 2 , Stefan Taubert 1 1 Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada, 2 Michael Smith laboratories, University of British Columbia, Vancouver, BC, Canada Transforming growth factor β (TGF-β) signaling plays a pivotal role to regulate cell proliferation, apoptosis, organ development and cancer metastasis. The downstream effector of TGF-β signaling, Smad proteins, interact with variety of partner proteins to achieve their function. To better understand Smad signaling, we performed immunoprecipitation (IP) of C. elegans DAF-8/R-Smad followed by mass spectrometry and identified the TGFβI receptor DAF- 1 and HID-1 (High Temperature induced Dauer) as a novel DAF-8 interacting proteins. Others previously showed that HID-1 interacts physically with the E3 ubiquitin ligase WWP-1, which is required for dietary restriction (DR)-induced life span extension. To test whether HID-1 also affects longevity, we determined the life spans of hid-1 mutants and of worms over-expressing hid-1 in ad libitum (AL) and DR conditions. The hid-1 mutants showed a shortened adult life span, whereas hid-1 overexpression extended life span in AL and DR conditions. Furthermore, we found that over-expression of the TGFβI receptor daf-1 (daf-1oe) also extended worm life span in DR conditions, and this life span extension was dependent on hid-1. RNAi against skn- 1/bZIP or pha-4/FoxA transcription factors only partially suppressed the daf-1oe mediated life span extension, indicating that TGF-β regulates DR-induced life span in parallel to skn-1 and pha-4. Furthermore, daf-7/TGFβ1 transcript and DAF-1 protein levels were maintained in DR conditions but decreased in AL fed worms over time, indicating that DR conditions may lead to sustained TGF-β signaling. Lastly, because mobilization of stored lipids may be affected in DR, we quantified the expression of several lipid metabolism genes. We found that several lipid β-oxidation genes, including daf-22, were induced by DR in daf-7 dependent manner, and that DR failed to extend the life span of daf-22 mutants. Overall, our results suggest that TGF-β signaling plays an important role in DR-induced life span extension, possibly be controlling lipid metabolism genes. Session 3 21
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