EVOLUTION, MUTATIONS, AND HUMAN LONGEVITY - EUROPEAN ROYAL AND NOBLE FAMILIES

The evolutionary theory of aging predicts that the equilibrium gene fr equency for deleterious mutations should increase with age at onset of mutation action because of weaker (postponed) selection against later -acting mutations. According to this mutation accumulation hypothesis, one would expect the genetic variability for survival (additive genet ic variance) to increase with age. The ratio of additive genetic varia nce to the observed phenotypic variance (the heritability of longevity ) can be estimated most reliably as the doubled slope of the regressio n line for offspring life span on paternal age at death. Thus, if long evity is indeed determined by late-acting deleterious mutations, one w ould expect this slope to become steeper at higher paternal ages. To t est this prediction of evolutionary theory of aging, we computerized a nd analyzed the most reliable and accurate genealogical data on longev ity in European royal and noble families. Offspring longevity for each sex (8409 records for males and 3741 records for females) was conside red as a dependent variable in the multiple regression model and as a function of three independent predictors: paternal age at death (for e stimation of heritability of life span), paternal age at reproduction (control for parental age effects), and cohort life expectancy (contro l for cohort and secular trends and fluctuations). We found that the r egression slope for offspring longevity as a function of paternal long evity increases with paternal longevity, as predicted by the evolution ary theory of aging and by the mutation accumulation hypothesis in par ticular.