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2000 | 47 | 2 | 269-279
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Aging and longevity genes.

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The genetics of aging has made substantial strides in the past decade. This progress has been confined primarily to model organisms, such as filamentous fungi, yeast, nematodes, fruit flies, and mice, in which some thirty-five genes that determine life span have been cloned. These genes encode a wide array of cellular functions, indicating that there must be multiple mechanisms of aging. Nevertheless, some generalizations are already beginning to emerge. It is now clear that there are at least four broad physiological processes that play a role in aging: metabolic control, resistance to stress, gene dysregulation, and genetic stability. The first two of these at least are common themes that connect aging in yeast, nematodes, and fruit flies, and this convergence extends to caloric restriction, which postpones senescence and increases life span in rodents. Many of the human homologs of the longevity genes found in model organisms have been identified. This will lead to their use as candidate human longevity genes in population genetic studies. The urgency for such studies is great: The population is graying, and this research holds the promise of improvement in the quality of the later years of life.
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  • 1. Rose, M.R. (1991) Evolutionary Biology of Aging. Oxford University Press, New York.
  • 2. Warner, H.R., Butler, R.N., Sprott, R.L. & Schneider, E.L. (1987) Modern Biological Theories of Aging. Raven Press, New York.
  • 3. Jazwinski, S.M. (1996) Longevity, genes, and aging. Science 273, 54-59.
  • 4. Jazwinski, S.M., Kim, S., Lai, C.-Y. & Benguria, A. (1998) Epigenetic stratification: The role of individual change in the biological aging process. Exp. Gerontol. 33, 571-580.
  • 5. Rowe, J.W. & Kahn, R.L. (1998) Successful Aging. Pantheon Books, New York.
  • 6. Glass, T.A., de Leon, C.M., Marottoli, R.A. & Berkman, L.F. (1999) Population based study of social and productive activities as predictors of survival among elderly Americans. Brit. Med. J. 319, 478-483.
  • 7. Bassett, D.E., Boguski, M.S., Spencer, F., Reeves, R., Kim, S-h., Weaver, T. & Hieter, P. (1997) Genome cross-referencing and XREFdb: Implications for the identification and analysis of genes mutated in human disease. Nature Genet. 15, 339-344.
  • 8. Mortimer, R.K. & Johnston, J.R. (1959) Life span of individual yeast cells. Nature 183, 1751-1752.
  • 9. Muller, I., Zimmermann, M., Becker, D. & Flomer, M. (1980) Calendar life span versus budding life span of Saccharomyces cerevisiae. Mech. Ageing Dev. 12, 47-52.
  • 10. Kirchman, P.A., Kim, S., Lai, C.-Y. & Jazwinski, S.M. (1999) Interorganelle signaling is a determinant of longevity in Saccharomyces cerevisiae. Genetics 152, 179-190.
  • 11. Kale, S.P. & Jazwinski, S.M. (1996) Differential response to UV stress and DNA damage during the yeast replicative life span. Dev. Genet. 18, 154-160.
  • 12. Wawryn, J., Krzepilko, A., Myszka, A. & Bilinski, T. (1999) Deficiency in superoxide dismutases shortens life span of yeast cells. Acta Biochim. Polon. 46, 249-253.
  • 13. Shama, S., Kirchman, P.A., Jiang, J.C. & Jazwinski, S.M. (1998) Role of RAS2 in recovery from chronic stress: Effect on yeast life span. Exp. Cell Res. 245, 368-378.
  • 14. Shama, S., Lai, C.-Y., Antoniazzi, J.M., Jiang, J.C. & Jazwinski, S.M. (1998) Heat stress-induced life span extension in yeast. Exp. Cell Res. 245, 379-388.
  • 15. Kim, S., Villeponteau, B. & Jazwinski, S.M. (1996) Effect of replicative age on transcriptional silencing near telomeres in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 219, 370-376.
  • 16. Smeal, T., Claus, J., Kennedy, B., Cole, F. & Guarente, L. (1996) Loss of transcriptional silencing causes sterility in old mother cells of S. cerevisiae. Cell 84, 633-642.
  • 17. Jazwinski, S.M. (1990) Aging and senescence of the budding yeast Saccharomyces cerevisiae. Mol. Microbiol. 4, 337-343.
  • 18. Kim, S., Benguria, A., Lai, C.-Y. & Jazwinski, S.M. (1999) Modulation of life-span by histone deacetylase genes in Saccharomyces cerevisiae. Mol. Biol. Cell 10, 3125-3136.
  • 19. Motizuki, M. & Tsurugi, K. (1992) The effect of aging on protein synthesis in the yeast Saccharomyces cerevisiae. Mech. Ageing Dev. 64, 235-245.
  • 20. Sinclair, D.A. & Guarente, L. (1997) Extrachromosomal rDNA circles A cause of aging in yeast. Cell 91, 1033-1042.
  • 21. Jazwinski, S.M. (1999) The RAS genes: A homeostatic device in Saccharomyces cerevisiae longevity. Neurobiol. Aging 20, 471- 478.
  • 22. Tissenbaum, H.A. & Ruvkun, G. (1998) An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans. Genetics 148, 703-717.
  • 23. Paradis, S. & Ruvkun, G. (1998) Caenorhabditis elegans Akt/PKB transduces insulin-like receptor signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev. 12, 2488-2498.
  • 24. Ogg, S. & Ruvkun, G. (1998) The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway. Mol. Cell 2, 887-893.
  • 25. O'Brien, R.M., Noisin, E.L., Suwanichkul, A., Yamasaki, T., Lucas, P.C., Wang, J.C., Powell, D.R. & Granner, D.K. (1995) Hepatic nuclear factor-3 and hormone-regulated expression of the phosphoenolpyruvate carboxykinase and insulin-like growth factor-binding protein 1 genes. Mol. Cell. Biol. 15, 1747-1758.
  • 26. Vanfleteren, J.R. & De Vreese, A. (1995) The gerontogenes age-1 and daf-2 determine metabolic rate potential in aging Caenorhabditis elegans. FASEB J. 9, 1355-1361.
  • 27. Larsen, P.L., Albert, P.S. & Riddle, D.L. (1995) Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics 139, 1567-1583.
  • 28. Hsin, H. & Kenyon, C. (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399, 362-366.
  • 29. Taub, J., Lau, J.K., Ma, C., Hahn, J.H., Hoque, R., Rothblatt, J. & Chalfie, M. (1999) A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants. Nature 399, 162-166.
  • 30. Murakami, S. & Johnson, T.E. (1996) A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 143, 1207-1218.
  • 31. Ewbank, J.J., Bames, T.M., Lakowski, B., Lussier, M., Bussey, H. & Hekimi, S. (1997) Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1. Science 275, 980-983.
  • 32. Felkai, S., Ewbank, J.J., Lemieux, J., Labbe, J.-C., Brown, G.G. & Hekimi, S. (1999) CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans. EMBO J. 18, 1783-1792.
  • 33. Luckinbill, L.S., Arking, R., Clare, M.J., Cirocco, W.C. & Buck, S.A. (1984) Selection for delayed senescence in Drosophila melanogaster. Evolution 38, 996-1003.
  • 34. Rose, M.R. (1984) Laboratory evolution of postponed senescence in Drosophila melanogaster. Evolution 38, 1004-1010.
  • 35. Jazwinski, S.M. (2000) Coordination of metabolic activity and stress resistance in yeast longevity; in The Molecular Genetics of Aging (Hekimi, S., ed.) pp. 21-44, Springer- Verlag, Berlin.
  • 36. Orr, W.C. & Sohal, R.S. (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263, 1128-1130.
  • 37. Sun, J. & Tower, J. (1999) FLP recombinase- mediated induction of Cu/Zn-superoxide dismutase transgene expression can extend the life span of adult Drosophila melanogaster flies. Mol. Cell. Biol. 19, 216-228.
  • 38. Parkes, T.L., Elia, A.J., Dickinson, D., Hilliker, A.J., Phillips, J.P. & Boulianne, G.L. (1998) Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet. 19, 171-174.
  • 39. Lin, Y.J., Seroude, L. & Benzer, S. (1998) Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282, 943-946.
  • 40. Masoro, E. (1995) Dietary restriction. Exp. Gerontol. 30, 291-298.
  • 41. Lee, C.-K., Klopp, R.G., Weindruch, R. & Prolla, T.A. (1999) Gene expression profile of aging and its retardation by caloric restriction. Science 285, 1390-1393.
  • 42. Brown-Borg, H., Borg, K.E., Meliska, C.J. & Bartke, A. (1996) Dwarf mice and the ageing process. Nature 384, 33.
  • 43. Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, P.P., Lanfrancone, L. & Pelicci, P.G. (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402, 309-313.
  • 44. Cattanach, B.L. (1974) Position effect variegation in the mouse. Genet. Res. 23, 291-306.
  • 45. de Haan, G., Gelman, R., Watson, A., Yunis, E. & Van Zant, G. (1998) A putative gene causes variability in lifespan among genotypically identical mice. Nature Genet. 19, 114-116.
  • 46. Jiang, J.C., Kirchman, P.A., Zagulski, M., Hunt, J. & Jazwinski, S.M. (1998) Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human. Genome Res. 8, 1259-1272.
  • 47. Lander, E.S. & Schork, N.J. (1994) Genetic dissection of complex traits. Science 265, 2037-2048.
  • 48. Schachter, F., Faure-Delanef, L., Guenot, F., Rouger, H., Froguel, P. Lesueur-Ginot, L. & Cohen, D. (1994) Genetic associations with human longevity at the APOE and ACE loci. Nature Genet. 6, 29-32.
  • 49. Vaupel, J.W., Carey, J.R., Christensen, K., Johnson, T.E., Yashin, A.I., Holm, N.V., Iachine, I.A., Kannisto, V., Khazaeli, A.A., Liedo, P., Longo, V.D., Zeng, Y., Manton, K.G. & Curtsinger, J.W. (1998) Biodemographic trajectories of longevity. Science 280, 855- 860.
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