Center on Aging, NORC at the University of Chicago
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.
data also are useful for testing the prediction of the disposable soma
human longevity comes with the cost of impaired reproductive success.
that in contrast to previous reports by other authors, woman's
longevity is not associated with infertility. Thus, the concept of
infertility cost for human longevity is not supported by data, when
are carefully cross-checked, cleaned and reanalyzed. These results
the importance of high quality genealogical data for genetic studies of
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.
Gavrilov, L.A. Consanguinity
and human longevity: Findings from the International Centenarian Study.
Gerontologist, 2001, 41 (Sp. issue): 87-87.
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.