Genetics of Human Longevity

Genetics of Human Longevity: New Ideas & Findings

Natalia Gavrilova

Center on Aging, NORC at the University of Chicago

(Abstract of presentation at the International Conference on Longevity, Sydney, Australia, March 5-7, 2004)

In contrast to the remarkable progress in the genetics of yeast and nematode aging, little is known about genes that control human longevity. What is behind the records of extreme human longevity: just lucky chance, favorable environment, or 'good' genes? How to resolve the apparent controversy between strong familial clustering of human longevity, and poor resemblance in lifespan among blood relatives?

We applied methods of genetic epidemiology and survival analysis to family-linked data on human lifespan. Special efforts were undertaken to collect detailed and reliable human genealogies an important data source for genetic studies of human longevity. We found that the dependence of offspring lifespan on parental lifespan is essentially non-linear, with very weak resemblance before parental lifespan of 80 years and very steep offspring-parent dependence (high narrow-sense heritability) for longer lived parents. There is no correlation between lifespan of spouses, who share familial environment. These observations suggest that chances to survive beyond age 80 are significantly influenced by genetic factors rather than shared familial environment. These findings explain the existing longevity paradox: although the heritability estimates for lifespan are rather low, the exceptional longevity has a strong familial association.

We also tested the prediction of mutation theory of aging that accumulation of mutations in parental germ cells may affect progeny lifespan when progeny was conceived to older parents. We found that daughters conceived to older fathers live shorter lives, while sons are not affected. Maternal age effects on lifespan of adult progeny are negligible compared to effects of paternal age, which is consistent with the notion of higher rates of DNA copy-errors in paternal germ cells caused by more intensive cell divisions during spermatogenesis.

Genealogical data also are useful for testing the prediction of the disposable soma theory that human longevity comes with the cost of impaired reproductive success. We found that in contrast to previous reports by other authors, woman's exceptional longevity is not associated with infertility. Thus, the concept of heavy infertility cost for human longevity is not supported by data, when these data are carefully cross-checked, cleaned and reanalyzed. These results demonstrate the importance of high quality genealogical data for genetic studies of human longevity.

Relevant Publications:

Gavrilov, L.A., Gavrilova, N.S. Early-life factors modulating lifespan. In: Rattan, S.I.S. (Ed.).Modulating Aging and Longevity. Kluwer Academic Publishers, Dordrecht, The Netherlands, 2003, 27-50.

Gavrilova, N.S., Gavrilov, L.A. Evolution of Aging. In: David J. Ekerdt (eds.) Encyclopedia of Aging, New York, Macmillan Reference USA, 2002, vol. 2, 458-467.

Gavrilov, L.A., Gavrilova, N.S. Human longevity and parental age at conception. In: J.-M.Robine et al. (eds.) Sex and Longevity: Sexuality, Gender, Reproduction, Parenthood, Berlin, Heidelberg: Springer-Verlag, 2000, 7-31.

Gavrilova N.S., Gavrilov L.A., Evdokushkina, G.N., Semyonova, V.G. Early-life predictors of human longevity: Analysis of the 19th Century birth cohorts. Annales de Demographie Historique, 2003, 2: 177-198.

Gavrilova NS, Gavrilov LA, Semyonova VG, Evdokushkina GN. Does Exceptional Human Longevity Come With High Cost of Infertility? Testing the Evolutionary Theories of Aging. Biogerontology. 4(Suppl.1): 35-35, 19 Sep 2003

Gavrilov, L.A., Gavrilova, N.S. Evolutionary theories of aging and longevity. TheScientificWorldJOURNAL, 2002, 2: 339-356. Available: http://www.thescientificworld.com/

Gavrilova, N.S., Gavrilov, L.A. When does human longevity start?: Demarcation of the boundaries for human longevity. Journal of Anti-Aging Medicine, 2001, 4(2): 115-124.

Gavrilov L.A., Gavrilova N.S. Epidemiology of human longevity: The search for appropriate methodology. Journal of Anti-Aging Medicine, 2001, 4(1): 13-30.

Gavrilov, L.A., Gavrilova, N.S. Biodemographic study of familial determinants of human longevity. Population: An English Selection, 2001, 13(1): 197-222.

Gavrilova, N.S., Gavrilov, L.A. Consanguinity and human longevity: Findings from the International Centenarian Study. Gerontologist, 2001, 41 (Sp. issue): 87-87.

Gavrilov, L.A., Gavrilova, N.S. Is there a reproductive cost for human longevity? Journal of Anti-Aging Medicine, 1999, 2(2): 121-123.

Gavrilova, N.S., Gavrilov, L.A., Evdokushkina G.N., Semyonova, V.G., Gavrilova, A.L., Evdokushkina, N.N., Kushnareva, Yu.E., Kroutko, V.N., Andreyev, A.Yu. Evolution, mutations and human longevity. Human Biology, 1998, 70(4): 799-804.

Gavrilov, L.A., Gavrilova, N.S. Parental age at conception and offspring longevity. Reviews in Clinical Gerontology, 1997, 7: 5-12.

Gavrilov L.A., Gavrilova, N.S., Kroutko, V.N., Evdokushkina, G.N., Semyonova, V.G., Gavrilova, A.L., Lapshin, E.V., Evdokushkina N.N., Kushnareva, Yu.E. Mutation load and human longevity. Mutation Research, 1997, 377(1): 61-62.

Gavrilov, L.A., Gavrilova, N.S. When Fatherhood Should Stop? Letter. Science, 1997, 277(5322): 17-18.

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Genetics of Human Longevity