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Why do we age?

Abstract

The evolutionary theory of ageing explains why ageing occurs, giving valuable insight into the mechanisms underlying the complex cellular and molecular changes that contribute to senescence. Such understanding also helps to clarify how the genome shapes the ageing process, thereby aiding the study of the genetic factors that influence longevity and age-associated diseases.

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Figure 1: Evolutionary theories of ageing.

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References

  1. Kirkwood, T. B. L. & Cremer, T. Cytogerontology since 1881: a reappraisal of August Weismann and a review of modern progress . Hum. Genet. 60, 101–121 (1982).

    Article  CAS  PubMed  Google Scholar 

  2. Rose, M. R. Evolutionary Biology of Ageing (Oxford Univ. Press, New York, 1991).

    Google Scholar 

  3. Austad, S. N. Why We Age (Wiley, New York, 1997).

    Google Scholar 

  4. Kirkwood, T. B. L. Time of Our Lives: The Science of Human Ageing (Oxford Univ. Press, New York, 1999).

    Google Scholar 

  5. Finch, C. E. Longevity, Senescence and the Genome (Chicago Univ. Press, Chicago, 1990).

    Google Scholar 

  6. Charlesworth, B. Evolution in Age-Structured Populations (Cambridge Univ. Press, Cambridge, 1994).

    Book  Google Scholar 

  7. Medawar, P. B. An Unsolved Problem of Biology (Lewis, London, 1952 ).

    Google Scholar 

  8. Martin, G. M., Austad, S. N. & Johnson, T. E. Genetic analysis of aging: role of oxidative damage and environmental stresses. Nature Genet. 13, 25–34 (1996).

    Article  CAS  PubMed  Google Scholar 

  9. Williams, G. C. Pleiotropy, natural selection and the evolution of senescence. Evolution 11, 398–411 ( 1957).

    Article  Google Scholar 

  10. Kirkwood, T. B. L. Evolution of ageing. Nature 270, 301– 304 (1977).

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Kirkwood, T. B. L. Human senescence. BioEssays 18, 1009– 1016 (1996).

    Article  CAS  PubMed  Google Scholar 

  12. Phelan, J. P. & Austad, S. N. Natural selection, dietary restriction and extended longevity. Growth Dev. Aging 53, 4–6 (1989).

    CAS  PubMed  Google Scholar 

  13. Berry, R. J. & Bronson, F. H. Life history and bioeconomy of the house mouse. Biol. Rev. 67, 519– 550 (1992).

    Article  CAS  PubMed  Google Scholar 

  14. Bell, G. Evolutionary and nonevolutionary theories of senescence. Am. Nat. 124, 600–603 ( 1984).

    Article  ADS  Google Scholar 

  15. Martinez, D. E. Mortality patterns suggest lack of senescence in hydra. Exp. Gerontol. 33, 217–225 ( 1997).

    Article  Google Scholar 

  16. Rose, M. R. & Charlesworth, B. A test of evolutionary theories of senescence. Nature 287, 141– 142 (1980).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Luckinbill, L. S., Arking, R., Clare, M. J., Cirocco, W. C. & Buck, S. A. Selection of delayed senescence in Drosophila melanogaster. Evolution 38, 996– 1003 (1984).

    Article  PubMed  Google Scholar 

  18. Partridge, L., Prowse, N. & Pignatelli, P. Another set of responses and correlated responses to selection on age of reproduction in Drosophila melanogaster. Proc. R. Soc. Lond. B 266, 255–261 (1999).

    Article  CAS  Google Scholar 

  19. Buck, S., Vettraino, J., Force, A. G. & Arking, R. Extended longevity in Drosophila is consistently associated with a decrease in larval viability. J. Gerontol. A 55, B292–B301 (2000).

    Article  CAS  Google Scholar 

  20. Zwaan, B. J., Bijlsma, R. & Hoekstra, R. F. Direct selection on lifespan in Drosophila melanogaster . Evolution 49, 649– 659 (1995).

    Article  PubMed  Google Scholar 

  21. Stearns, S. C., Ackermann, M., Doebeli, M. & Kaiser, M. Experimental evolution of aging, growth, and reproduction in fruitflies. Proc. Natl Acad. Sci. USA 97, 3309– 3313 (2000).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sgró, C. M. & Partridge, L. A delayed wave of death from reproduction in Drosophila. Science 286, 2521–2524 (1999).

    Article  PubMed  Google Scholar 

  23. Van Voorheis, W. A. & Ward, S. Genetic and environmental conditions that increase longevity in Caenorhabditis elegans decrease metabolic rate. Proc. Natl Acad. Sci. USA 95, 11399–11403 (1999).

    Article  ADS  Google Scholar 

  24. Johnson, T. E. & Hutchinson, E. W. Absence of strong heterosis for life span and other life history traits in Caenorhabditis elegans. Genetics 134, 465– 474 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Walker, D. W., McColl, G., Jenkins, N. L., Harris, J. & Lithgow, G. J. Evolution of lifespan in C. elegans. Nature 405, 296– 297 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  26. Stearns, S. C. & Partridge, L. in Handbook of the Biology of Aging (eds Masoro, E. J. & Austad, S. N.) (Academic, San Diego, in the press).

  27. Service, P. M., Hutchinson, E. W. & Rose, M. R. Multiple genetic mechanisms for the evolution of senescence in Drosophila melanogaster. Evolution 42, 708–716 (1988).

    Article  CAS  PubMed  Google Scholar 

  28. Hughes, K. A. & Charlesworth, B. A genetic analysis of senescence in Drosophila. Nature 367, 64– 66 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Charlesworth, B. & Hughes, K. A. Age-specific inbreeding depression and components of genetic variance in relation to the evolution of senescence. Proc. Natl Acad. Sci. USA 93, 6140–6145 (1996).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  30. Promislow, D. E. L., Tatar, M., Khazaeli, A. A. & Curtsinger, J. W. Age-specific patterns of genetic variation in Drosophila melanogaster. I. Mortality. Genetics 143, 839– 848 (1995).

    Google Scholar 

  31. Shaw, F. H., Promislow, D. E. L., Tatar, M., Hughes, K. A. & Geyes, C. J. Toward reconciling inferences concerning genetic variation in Drosophila melanogaster. Genetics 152, 553–566 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Austad, S. N. Retarded senescence in an insular population of opossums. J. Zool. 229, 695–708 ( 1993).

    Article  Google Scholar 

  33. Keller, L. & Genoud, M. Extraordinary lifespans in ants: a test of evolutionary theories of aging. Nature 389 , 958–960 (1997).

    Article  ADS  CAS  Google Scholar 

  34. Ricklefs, R. E. Evolutionary theories of aging: confirmation of a fundamental prediction, with implications for the genetic basis and evolution of life span. Am. Nat. 152, 24–44 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  35. Sohal, R. S., Ku, H.-H. & Agarwal, S. Biochemical correlates of longevity in two closely-related rodent species. Biochem. Biophys. Res. Comm. 196, 7–11 (1993).

    Article  CAS  PubMed  Google Scholar 

  36. Ku, H.-H., Brunk, U. T. & Sohal, R. S. Relationship between mitochondrial superoxide and hydrogen-peroxide production and longevity of mammalian-species. Free Radical Biol. Med. 15, 621–627 (1993).

    Article  CAS  Google Scholar 

  37. Barja, G. & Herrero, A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals . FASEB J. 14, 312–318 (2000).

    Article  CAS  PubMed  Google Scholar 

  38. Herrero, A. & Barja, G. 8-oxo-deoxyguanosine levels in heart and brain mitochondrial and nuclear DNA of two mammals and three birds in relation to their different rates of aging. Aging Clin. Exp. Res. 11, 294–300 ( 1999).

    Article  CAS  Google Scholar 

  39. Sell, D. R. et al. Longevity and the genetic determination of collagen glycoxidation kinetics in mammalian senescence. Proc. Natl Acad. Sci. USA 93, 485–490 (1996).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kirkwood, T. B. L. DNA, mutations and aging. Mut. Res. 219, 1–7 (1989).

    Article  CAS  Google Scholar 

  41. Grube, K. & Bürkle, A. Poly(ADP-ribose) polymerase activity in mononuclear leukocytes of 13 mammalian species correlates with species-specific life span. Proc. Natl Acad. Sci. USA 89, 11759–11763 (1992).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ogburn, C. E. et al. Cultured renal epithelial cells from birds and mice: enhanced resistance of avian cells to oxidative stress and DNA damage. J. Gerontol. 53, B287–B292 ( 1998).

    Article  CAS  Google Scholar 

  43. Kapahi, P., Boulton, M. E. & Kirkwood, T. B. L. Positive correlation between mammalian life span and cellular resistance to stress. Free Radical Biol. Med. 26, 495–500 (1999).

    Article  CAS  Google Scholar 

  44. Sohal, R. S. & Donato, H. Effects of experimentally altered life span on the accumulation of fluorescent age pigment in the housefly, Musca domestica. Exp. Gerontol. 13, 335–341 (1978).

    Article  CAS  PubMed  Google Scholar 

  45. Austad, S. N. Life extension by dietary restriction in the bowl and doily spider, Frontinella pyramitela. Exp. Gerontol. 24, 83– 92 (1989).

    Article  CAS  PubMed  Google Scholar 

  46. Klass, M. & Hirsh, D. Non-ageing developmental variant of Caenorhabditis elegans. Nature 260, 523–525 (1976).

    Article  ADS  CAS  PubMed  Google Scholar 

  47. Anderson, G. L. Responses of dauer larvae of Caenorhabditis elegans (Nematoda: Rhabditidae) to thermal stress and oxygen deprivation. Can. J. Zool. 56, 1786–1791 (1978).

    Article  Google Scholar 

  48. Lithgow, G. J. in Handbook of the Biology of Aging (eds Schneider, E. L. & Rowe, J. W.) 55–73 (Academic, San Diego, 1996).

    Google Scholar 

  49. Vanfleteren, S. L. & De Vreese, A. Rate of aerobic metabolism and superoxide production rate potential in the nematode Caenorhabditis elegans. J. Exp. Zool. 274, 93– 100 (1996).

    Article  CAS  PubMed  Google Scholar 

  50. Weindruch, R. & Walford, R. L. The Retardation of Aging and Disease by Dietary Restriction (Thomas, Springfield, IL, 1988).

    Google Scholar 

  51. Masoro, E. J. Influence of caloric intake on aging and on the response to stressors. J. Toxicol. Environ. Health B Crit. Rev. 1, 243– 257 (1998).

    Article  CAS  PubMed  Google Scholar 

  52. Walford, R. L. & Spindler, S. R. The response to calorie restriction in mammals shows features also common to hibernation: a cross-adaptation hypothesis. J. Gerontol. 52, B179–B183 (1997).

    Article  CAS  Google Scholar 

  53. Shanley, D. P. & Kirkwood, T. B. L. Calorie restriction and aging: a life history analysis. Evolution 54, 740–750 (2000).

    Article  CAS  PubMed  Google Scholar 

  54. Stearns, S. C. The Evolution of Life Histories (Oxford Univ. Press, New York, 1992).

    Google Scholar 

  55. Partridge, L. & Barton, N. H. On measuring the rate of ageing . Proc. R. Soc. Lond. B 263, 1365– 1371 (1996).

    Article  ADS  Google Scholar 

  56. Hill, K. & Hurtado, A. M. Ache Life History: the Ecology and Demography of a Foraging People (de Gruyter, New York, 1996).

    Google Scholar 

  57. Hamilton, W. D. The moulding of senescence by natural selection. J. Theor. Biol. 12, 12–14 ( 1966).

    Article  CAS  PubMed  Google Scholar 

  58. Kirkwood, T. B. L. & Holliday, R. in The Biology of Human Ageing (eds Collins, A. J. & Bittles, A. H.) 1– 16 (Cambridge Univ. Press, Cambridge, 1986).

    Book  Google Scholar 

  59. Austad, S. N. Menopause: an evolutionary perspective. Exp. Gerontol. 29, 255–263 (1994).

    Article  CAS  PubMed  Google Scholar 

  60. Peccei, J. S. The origin and evolution of menopause: the altriciality-lifespan hypothesis . Ethol. Sociobiol. 16, 425– 449 (1995).

    Article  Google Scholar 

  61. Hawkes, K., O'Connell, J. F., Jones, N. G. B., Alvarez, H. & Charnov, E. L. Grandmothering, menopause, and the evolution of human life histories. Proc. Natl Acad. Sci. USA 95, 1336–1339 ( 1998).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  62. Shanley, D. P. & Kirkwood, T. B. L. Evolution of the human menopause. BioEssays (in the press).

  63. Packer, C., Tatar, M. & Collins, A. Reproductive cessation in female mammals. Nature 392, 807–822 ( 1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  64. Risch, N., Reich, E. W., Wishnick, M. M. & McCarthy, J. G. Spontaneous mutation and parental age in humans. Am. J. Hum. Genet. 41, 218–248 ( 1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Gavrilov, L. A. & Gavrilova, N. S. Parental age at conception and offspring longevity. Rev. Clin. Gerontol. 7, 5–12 (1997 ).

    Article  Google Scholar 

  66. Wallace, D. C. Mitochondrial diseases in man and mouse. Science 283 , 1482–1488 (1999).

    Article  ADS  CAS  PubMed  Google Scholar 

  67. Cummins, J. M. in Female Reproductive Aging (eds Te Velde, E. R., Pearson, P. L. & Broekmans, F. J.) 207–224 (Parthenon, Carnforth, UK, 2000).

    Google Scholar 

  68. Vieira, C. et al. Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster. Genetics 154 , 213–227 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Lee, C. K., Klopp, R. G., Weindruch, R. & Prolla, T. A. Gene expression profile of aging and its retardation by caloric restriction . Science 285, 1390–1393 (1999).

    Article  CAS  PubMed  Google Scholar 

  70. Finch, C. E. & Kirkwood, T. B. L. Chance, Development and Aging (Oxford Univ. Press, New York, 2000).

    Google Scholar 

  71. Vaupel, J. W. et al. Biodemographic trajectories of longevity. Science 280, 855–860 (1998).

    Article  CAS  PubMed  Google Scholar 

  72. Service, P. M., Hutchinson, E. W., Mackinley, M. D. & Rose, M. R. Resistance to environmental-stress in Drosophila melanogaster selected for postponed senescence. Physiol. Zool. 58, 380–389 (1985).

    Article  Google Scholar 

  73. Tatar, M. Evolution of senescence: longevity and the expression of heat shock proteins . Am. Zool. 39, 920–927 (1999).

    Article  CAS  Google Scholar 

  74. Lin, Y. J., Seroude, L. & Benzer, S. Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282 , 943–946 (1998).

    ADS  CAS  PubMed  Google Scholar 

  75. Migliaccio, E. et al. The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402, 309–313 (1999).

    Article  ADS  CAS  PubMed  Google Scholar 

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Kirkwood, T., Austad, S. Why do we age?. Nature 408, 233–238 (2000). https://doi.org/10.1038/35041682

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