Genetically Engineered Mice 37537. Gu, H., Marth, J. D., Orban, P. C., Mossmann, H., and Rajewsky, K. (1994) Deletionof a DNA polymerase beta gene segment in T cells using cell type-specifictargeting. Science 265, 103–106.38. Dymecki, S. (1996) A modular set of FIp, FRT, and lacZ fusion vectors for manipulatinggenes by site-specific recombination. Gene 171, 197–201.39. Dymecki, S. (1996) Flp recombinase promotes site-specific DNA recombinationin embryonic stem cells and transgenic mice. Proc. Natl. Acad. Sci. USA 93,6191–6196.40. Rossant, J. and Nagy, A. (1995) Genome engineering: the new mouse genetics.Nature Med. 1, 592–594.41. St-Onge, L., Furth, P. A., and Gruss, P. (1996) Temporal control of the Crerecombinase in transgenic mice by a tetracycline responsive promoter. Nucleic AcidRes. 24, 3875–3877.42. Erickson, R. P. (1996) Mouse models of human genetic disease: which mouse ismore like a man? BioEssays 18, 993–998.43. Yunis, E. J., Watson, A. L., Gelman, R. S., Sylvia, S. J., Bronson, R., and Dorf, M.E. (1984) Traits that influence longevity in mice. Genetics 108, 999–101.44. Gelman, R., Watson, A., Bronson, R., and Yunis, E. (1988) Murine chromosomalregions correlated with longevity. Genetics 118, 693–704.45. Dear, K. B., Salazar, M., Watson, A. L., Gelman, R. S., Bronson, R., and Yunis, E.J. (1992) Traits that influence longevity in mice: a second look. Genetics 132,229–239.46. Gerlai, R. (1996) Gene-targeting studies of mammalian behavior: is it the mutationor the background phenotype? Trends Neurosci. 19, 177–180.47. Crawley, J. N. (1996) Unusual behavior phenotypes of inbred mouse strains. TrendsNeurosci. 19, 181–182.48. Orr, W. C. and Sohal, R. S. (1994) Extension of life-span by overexpressionof superoxide dismutase and catalase in Drosophila melanogaster. Science 263,1128–1130.49. Goldstein, S. (1990) Replicative senescence: the human fibroblast comes of age.Science 249, 1129–1133.50. Ikram, Z., Norton, T., and Jat, P. S. (1994) The biological clock that measures themitotic lifespan of mouse embryonic fibroblasts continues to function in the presenceof simian virus 40 large tumor antigen. Proc. Natl. Acad. Sci. USA 91, 6448–6452.51. Narayanan, L., Fritzell, J. A., Baker, S. M., Liskay, R. M., and Glazer, P. M. (1997)Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatchrepair gene Pms2. Proc. Natl. Acad. Sci. USA 94, 3122–3127.52. Hsaio, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F.,and Cole, G. (1996) Correlative memory deficits, beta-amyloid elevation, and amyloidplaques in transgenic mice. Science 274, 99–103.53. Games, D., Adams, A., Alessandrini, R., Barbour, R., Berthelette, P., Blackwell, C.,Carr, T., Clemens, J., Donaldson, T., Gillespie, F., Guido, T., Hagopian, S., Wood-Johnson, K., Khan, K., Lee, M., Liebowitz, P., Leiberburg, I., Little, S., Masliah, E.,McConlogue, L., Montoya-Zavala, M., Mucke, L., Paganini, L., Penniman, E.,
376 AndersenPower, M., Schenk, D., Seubert, P., Snyder, B., Soriano, F., Tan, H., Vitale, J.,Wadsworth, S., Wolozin, B., and Zhao, J. (1995) Alzheimer-type neuropathologyin transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature373, 523–527.54. Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C. M., Perez-tur, J., Hutton, M.,Buee, L., Harigaya, Y., Yager, D., Morgan, D., Gordon, M. N., Holcomb, L., Refolo,L., Zenk, B., Hardy, J., and Younkin, S. (1996) Increased amyloid-beta42(43) inbrains of mice expressing mutant presenilin 1. Nature 383, 710–713.55. Holcomb, L., Gordon, M. N., McGowan, E., Yu, X., Benkovic, S., Jantzen, P., Wright,K., Saad, I., Mueller, R., Morgan, D., Sanders, S., Zehr, C., O’Campo, K., Hardy, J.,Prada, C. M., Eckman, C., Younkin, S., Hsiao, K., and Duff, K. (1998) AcceleratedAlzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursorprotein and presenilin I transgenes. Nat. Med. 4, 97–100.56. Duff, K. (1997) Alzheimertransgenic mouse models come of age. Trends Neurosci.20, 279–280.57. Hsiao, K. K., Borchelt, D. R., Olson, K., Johannsdottir, R., Kitt, C., Yunis, W., Xu,S., Eckman, C., Younkin, S., and Price, D. (1995) Age-related CNS disorder andearly death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursorproteins. Neuron 15, 1203–1218.58. Haynes, L., Linton, P. J., and Swain, S. L. (1997) Age-related changes in CDC4 Tcells of T cell receptor transgenic mice. Mech. Ageing Dev. 93, 95–105.59. Nakashima, Y., Plump, A. S., Raines, E. W., Breslow, J. L., and Ross, R. (1994)ApoE-deficient mice develop lesions of all phases of atherosclerosis throughoutthe arterial tree. Arteriosclerosis Thromb. 14, 133–140.60. Palinski, W., Ord, V. A., Plump, A. S., Breslow, J. L., Steinberg, D., and Witztum, J.L. (1994) ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis.Demonstration of oxidation-specific epitopes in lesions and high titers ofautoantibodies to malondialdehyde-lysine in serum. Arteriosclerosis Thromb. 14,605–616.61. Bellosta, S., Mahley, R. W., Sanan, D. A., Murata, J., Newland, D. L., Taylor, J. M.,and Pitas, R. E. (1995) Macrophage-specific expression of human apolipoprotein Ereduces atherosclerosis in hypercholesterol emi c apolipoprotei n E-null mice. J. Clin.Invest. 96, 2170–2179.62. van Vlijmen, B. J., van den Maagdenberg, A. M., Gijbels, M. J., van der Boom, H.,HogenEsch, H., Frants, R. R., Hofker, M. H., and Havekes, L. M. (1994) Dietinducedhyperlipoproteinemi a and atherosclerosis in apolipoprotein E3*-Leidentransgenic mice. J. Clin. Invest. 93, 4 1403–41410.63. Fazio, S., Horie, Y., Simonet, W. S., Weisgraber, K. H., Taylor, J. M., and Rall, S.C., Jr. (1994) Altered lipoprotein metabolism in transgenic mice expressing lowlevels of a human receptor-binding-defective apolipoprotein E. J. Lipid Res. 35,408–416.64. van Vlijmen, B. J., van Dijk, K. W., van’t Hof, H. B., van Gorp, P. J., van der Zee,A., van der Boom, H., Breuer, M. L., Hofker, M. H., and Havekes, L. M. (1996) hrthe absence of endogenous mouse apolipoprotein E, apolipoprotein E*2(Arg-l58
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Understanding Aging 9the intestine
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Understanding Aging 172. Pearl, R.
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Understanding Aging 1945. Perovic,
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24 Cristofalo, Volker, and Allenmen
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52 Cristofalo, Volker, and Allen125
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54 Pawelecdiluted cells on an irrad
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56 Pawelec3. Method3.1. Source of C
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Telomeres and Replicative Senescenc
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Detection of Molecular Events 73hav
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Detection of Molecular Events 8310.
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86 Kirk and Millerexperiments on un
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88 Kirk and MillerFig. 1. (A) Analy
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98 Engel, Adibzadeh, and PawelecPCR
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Assessing Antioxidant Status 137Tab
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Assessing Antioxidant Status 139add
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160 van der Schanswithin 1 h, after
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166 van der SchansThe calculations
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8-oxoguanine Levels in Nuclear DNA
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8-oxoguanine Levels in Nuclear DNA
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8-oxoguanine Levels in Nuclear DNA
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8-oxoguanine Levels in Nuclear DNA
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Mutation and the Aging Process 1791
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Mutation and the Aging Process 181m
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Mutation and the Aging Process 183b
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Mutation and the Aging Process 1853
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Mutation and the Aging Process 1871
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190 HouThe HPRT mutational spectrum
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Susceptibility of LDL to Oxidation
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Susceptibility of LDL to Oxidation
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Susceptibility of LDL to Oxidation
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Susceptibility of LDL to Oxidation
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222 Miquellipoperoxides and malonal
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224 Miquelat 4°C. Protect this sol
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226 Miquel3.1. Animal AnesthesiaMed
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228 Miquelsteps to carry out a conv
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230 Miquelsuspending it over the so
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232 Miquelcontrast, washing with bu
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234 MiquelFig. 3. Electron microsco
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Damage to Mitochondria 23718Causes
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Damage to Mitochondria 239Fig. 1. E
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Damage to Mitochondria 2412. To obt
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Damage to Mitochondria 243synthesis
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Mitochondrial DNA Mutations 24519An
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Mitochondrial DNA Mutations 247F.P.
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Mitochondrial DNA Mutations 249desi
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Mitochondrial DNA Mutations 2514. M
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Mitochondrial DNA Mutations 253Fig.
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Mitochondrial DNA Mutations 25568°
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Mitochondrial DNA Mutations 257Fig.
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Mitochondrial DNA Mutations 2593. P
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Mitochondrial DNA Mutations 261X-10
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Mitochondrial DNA Mutations 26315.
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Mitochondrial DNA Mutations 269muta
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Mitochondrial DNA Mutations 27711.
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282 BeckmanWhatever the mechanism e
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284 BeckmanT-cell adherence to vasc
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286 BeckmanT3 hybridoma cells satis
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288 BeckmanHaving identified a cand
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290 Beckmanthe plates vigorously wi
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292 Grubeck-Loebenstein, Saurwein-T
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