Skip to main content

Advertisement

Log in

The genetics of exceptional human longevity

  • Prevention: Genetics And Risk Factor
  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

How we age as individuals is no doubt a complex interaction of genetic and environmental factors. Studies of certain populations with optimal environments and health-related behaviors, as well as twin studies, suggest that the average set of genetic variations should facilitate the average person’s ability to live to around age 85. Average life expectancies are lower than this because we generally fight survival advantage with bad health habits that can lead to premature aging, chronic illness, and death at a significantly younger age. Centenarians on the other hand live 15–25 years beyond what the average collection of us are able to achieve. Many of them have a history of aging relatively slowly, and either markedly delaying or even escaping lethal diseases associated with aging (Alzheimer’s disease, stroke, cancer, cardiovascular disease, and diabetes). In order to live to such old age, centenarians are less likely to have genetic and environmental exposures that would cause at least lethal diseases at younger ages. Demographic selection is the drop out within a cohort, of genotypes linked to age-related lethal diseases and premature mortality as the cohort achieves older and older age. The results is a very old cohort that lacks these genotypes relative to younger age groups. Recent pedigree and molecular genetic studies indicate that scientists can use this selection to their advantage in discerning genotypes that play important roles in delaying or escaping diseases such as Alzheimer’s disease, and in slowing the aging process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Allard M. (1991) A la Recherche du Secret des Centeraires. Le Cherche-Midi, Paris.

    Google Scholar 

  • Alpert L., DesJardines B., Vaupel J., et al. (1998) Extreme longevity in two families. A report of multiple centenarians within single generations, in Age validation of the extreme old. Odense monographs on population aging 4. (Jeune B. and Vaupel J., eds.), Odense University Press, Odense.

    Google Scholar 

  • Baggio G., Donazzan S., Monti D., et al. (1998) Lipoprotein(a) and lipoprotein profile in healthy centenarians: a reappraisal of vascular risk factors. FASEB J. 12, 433–437.

    PubMed  CAS  Google Scholar 

  • Barbagallo C. M., Averna M. R., Frada G., et al. (1995) Plasma lipid apolipoprotein and Lp(a) levels in elderly normolipidemic women: relationships with coronary heart disease and longevity. Gerontology 41, 260–266.

    Article  PubMed  CAS  Google Scholar 

  • Barzilai N., Gabriely I., Gabriely M., et al. (2001) Offspring of centenarians have a favorable lipid profile. J. Am. Geriatr. Soc. 49, 76–79.

    Article  PubMed  CAS  Google Scholar 

  • Beard B. B. (1991) Centenarians, The New Generation. Greenwood Press, New York.

    Google Scholar 

  • Beregi E. (1990) Centenarians in Hungary. A Social and Demographic Study. Interdisciplinary Topics in Gerontology, vol. 27. Karger, Basel.

    Google Scholar 

  • Bocquet-Appel J. P. and Lucienne J. (1991) La transmission familiale de la longévité à Arthez d’Asson (1686–1899). Population 2, 327–347.

    Article  Google Scholar 

  • Finch C. E. and Tanzi R. E. (1997) Genetics of aging. Science 278, 407–411.

    Article  PubMed  CAS  Google Scholar 

  • Finkel T. and Holbrook N. J. (2000) Oxidants, oxidative stress and the biology of aging. Nature 408, 239–106.

    Article  PubMed  CAS  Google Scholar 

  • Fossel M. (2000) Cell senescence in human aging: a review of the theory. In Vivo 14, 29–34.

    PubMed  CAS  Google Scholar 

  • Guarente L. and Kenyon C. (2000) Genetic pathways that regulate ageing in model organisms. Nature 408, 255–262.

    Article  PubMed  CAS  Google Scholar 

  • Gudmundsson H., Gudbjartsson D. F., Frigge M., et al. (2000) Inheritance of human longevity in Iceland. Eur. J. Hum. Genet. 8, 743–749.

    Article  PubMed  CAS  Google Scholar 

  • Han E. and Hilsenbeck S. G. (2001) Array-based gene expression profiling to study aging. Mech. Ageing Dev. 122, 999–1018.

    Article  PubMed  CAS  Google Scholar 

  • Herskind A. M., McGue M., Iachine I. A., et al. (1996) Untangling genetic influences on smoking, body mass index and longevity: a multivariate study of 2464 Danish twins followed for 28 years. Hum. Genet. 98, 467–475.

    Article  PubMed  CAS  Google Scholar 

  • Herskind A. M., McGue M., Holm N. V., et al. (1996) The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900. Hum. Genet. 97, 319–323.

    PubMed  CAS  Google Scholar 

  • Hitt R., Young-Xu Y., and Perls T. (1999) Centenarians: the older you get, the healthier you’ve been. Lancet 354, 652.

    Article  PubMed  CAS  Google Scholar 

  • Karasawa A. (1979) Mental aging and its medico-social background in the very old Japanese. J. Gerontol. 34, 680–686.

    PubMed  CAS  Google Scholar 

  • Kenyon C. (2001) A conserved regulatory system for aging. Cell 105, 165–168.

    Article  PubMed  CAS  Google Scholar 

  • Kerber R. A., O’Brien E., Smith K. R., et al. (2001) Familial excess longevity in Utah genealogies. J. Gerontol. A. Biol. Sci. Med. Sci. 56, B130-B139.

    PubMed  CAS  Google Scholar 

  • Lander E. and Schork N. J. (1994) Genetic dissection of complex traits. Science 265, 2037–2048.

    Article  PubMed  CAS  Google Scholar 

  • Ljungquist B., Berg S., Lanke J., et al. (1998) The effect of genetic factors for longevity: a comparison of identical and fraternal twins in the Swedish Twin Registry. J. Gerontol. A. Biol. Sci. Med. Sci. 53, M441-M446.

    PubMed  CAS  Google Scholar 

  • Louhija J. (1994) Finnish Centenarians. Academic dissertation. University of Helsinki, Helsinki.

    Google Scholar 

  • Martin G. M. (1979) Genetic and evolutionary aspects of aging. Feder. Proc. 38, 1962–1967.

    CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Martin G. M. (1997) Genetics and the pathobiology of ageing. Philos. Trans. R. Soc. Lond. B Biol. Sci. 352, 1773–1780.

    Article  PubMed  CAS  Google Scholar 

  • McGue M., Vaupel J. W., Holm N., et al. (1993) Longevity is moderately heritable in a sample of Danish twins born 1870–1880. J. Gerontol. Biol. Sci. 48, B237-B244.

    CAS  Google Scholar 

  • Nemani M., Sahbatou M., Blanche H., et al. (2000) The efficiency of genetic analysis of DNA from aged siblings to detect chromosomal regions implicated in longevity. Mech. Aging Dev. 119, 25–39.

    Article  PubMed  CAS  Google Scholar 

  • Paolisso G., Gambardella A., Balbi V., et al. (1995) Body composition, body fat distribution and resting metabolic rate in healthy centenarians. Am. J. Clin. Nutrit. 62, 746–750.

    PubMed  CAS  Google Scholar 

  • Paolisso G., Tagliamonte M. R., Rizzo M. R., et al. (1998) Oxidative stress and advancing age: results in healthy centenarians. J. Am. Geriatr. Soc. 46, 833–838.

    PubMed  CAS  Google Scholar 

  • Perls T. T. (1995) The Oldest Old. Scientif. Am. 272, 70–75.

    Article  CAS  Google Scholar 

  • Perls T., Alpert L., and Fretts R. (1997) Middle aged mothers live longer. Nature 389, 133.

    Article  PubMed  CAS  Google Scholar 

  • Perls T., Wager C., Bubrick E., et al. (1998) Siblings of centenarians live longer. Lancet 351, 1560.

    Article  PubMed  CAS  Google Scholar 

  • Perls T., Wager C., Bubrick E., et al. (1998) Siblings of centenarians live longer. Lancet 351, 1560.

    Article  PubMed  CAS  Google Scholar 

  • Perls T. T. and Fretts R. (1998) Why women live longer than men. Sci. Am. Presents 9(2), 100–103.

    Google Scholar 

  • Perls T. T., Bochen K., Freeman M., et al. (1999) Validity of reported age and centenarian prevalence in New England. Age Ageing 28, 193–197.

    Article  PubMed  CAS  Google Scholar 

  • Perls T., Shea-Drinkwater M., Bowen-Flynn J., et al. (2000) Exceptional familial clustering for extreme longevity in humans. J. Am. Geriatr. Soc. 48, 1483–1485.

    PubMed  CAS  Google Scholar 

  • Perls T., Wilmoth J., Levenson R., et al. (2002) Life-long sustained mortality advantage of siblings of centenarians. Proc. Nat. Acad. Sci. 98, 8442–8447.

    Article  CAS  Google Scholar 

  • Poon L. W. (1992) The Georgian Centenarian Study. Baywood, Amityville, New York.

    Google Scholar 

  • Puca A. A., Daly M. J., Brewster S. J., et al. (2001) A genomewide scan for linkage to human exceptional longevity identifies a locus on chromosome 4. Proc. Natl. Acad. Sci. USA 98, 10505–10508.

    Article  PubMed  CAS  Google Scholar 

  • Rowe J. W. and Kahn R. L. (1998) Successful Aging. Random House, New York.

    Google Scholar 

  • Schächter F. (1998) Causes, effects, and constraints in the genetics of human longevity. Am. J. Hum. Genet. 62, 1008–1014.

    Article  PubMed  Google Scholar 

  • Vita A. J., Terry R. B., Hubert H. B., et al. (1998) Aging, health risks, and cumulative disability. N. Engl. J. Med. 338, 1035–1041.

    Article  PubMed  CAS  Google Scholar 

  • Wachter K. W. (1997) Between Zeus and the salmon: introduction, in Between Zeus and the Salmon. The Biodemography of Longevity National (Wachter K. W. and Finch C. E., eds.), Academy Press, Washington, DC.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas Perls.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perls, T., Kunkel, L.M. & Puca, A.A. The genetics of exceptional human longevity. J Mol Neurosci 19, 233–238 (2002). https://doi.org/10.1007/s12031-002-0039-x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-002-0039-x

Index Entries

Navigation