Evolution, mutations, and human longevity: European royal and noble families

The F ratio for each multiple regression was higher than 17.0, and all the regressions were statistically highly significant (p

+/- 0.02) born to fathers who lived 30 years or more (Table 1). At advanced paternal ages heritability estimates are much higher: 34% +/- 8% for sons (regression slope 0.17 +/- 0.04) and 58% +/- 12% for daughters (regression slope 0.29 +/- 0.06) born to fathers who lived 70 years or more (Table 1). It is worth noting that the heritability estimates were higher in daughters than in sons at all paternal ages, although this gender gap is statistically significant only at advanced paternal ages.

The higher heritability of longevity for daughters might be explained by their specific inheritance of the paternal X chromosome, which is richer in genetic information than the small paternal Y chromosome inherited by sons (Gavrilov and Gavrilova 1991, 1994).

Discussion

Our results demonstrate a significant increase in heritability of human longevity at advanced parental age at death (above age 60), predicted by the evolutionary theory of longevity and by the mutation accumulation hypothesis in particular. In fact, this observation is paradoxical because it is well known that there is strong selection against deleterious mutations and that by older ages most of such mutations should have been selected out. That is why one would expect an age-dependent decrease in heritability of human longevity rather than the increase in heritability found here. The fact that, despite strong selection against deleterious mutations, there is still significant genetic heterogeneity in the population with regard to longevity is remarkable. It should be noted, however, that the evolutionary theory of aging and the mutation accumulation theory are not the only possible explanations for the observed age-related increase in familial resemblance for longevity.

One of the alternative explanations of the observed phenomenon was proposed by one of the anonymous reviewers of this brief communication: Those persons who have parents that live long lives may have more similar environments, and those who have parents who die at an early age may have more variable social environments depending on other social situations. If this is the case, then the age-related increase in heritability estimates may be due to a decrease in environmental variation rather than to an increase in genetic variability. This may result in higher familial resemblance in longevity for those who have long-lived parents. This hypothesis could be tested through an analysis of longevity variance, because the hypothesis predicts that the observed total phenotypic variance for longevity of those born to long-lived parents should be less compared with those born to short-lived parents. Our analysis demonstrates, however, that the observed variance is essentially the same for all compared groups (standard deviation for longevity of the offspring surviving by age 30 is 14-15 years) and is not related to parental longevity. Thus the observed age-related increase in familial resemblance for human longevity could not be explained simply by the decrease in the environmental component of variance only. Further studies in this direction for larger sample sizes and other data sets are planned to clarify this issue.