adult age is associated with increasing mortality rates and decreasing fertility rates (1
). This age-related deterioration in functioning is partly subject to genetic regulation (2
). Several observational studies of human populations have demonstrated how these two life history traits are linked. Women bearing children at advanced ages have been shown to have better postmenopausal survival in natural fertility conditions (4
). For women born in 1896, childbearing after age 40 was found to be four times more frequent in centenarian women than in control women who died in their early seventies (10
). Contemporary women who reach advanced ages at natural menopause were also shown to experience significantly improved survival chances (7
), Experimental designs are also useful in demonstrating the close connection between fertility and mortality patterns. Experiments that select for late reproduction in female mice (14
) and Drosophila melanogaster
) have generated longer lived strains, which suggest that the timing of reproductive cessation in females is determined in part by the rate of senescence.
An important question in these studies is that the association measured between late female fertility and longevity within the same individual may arise for factors that are complex and often unobservable. Late female fertility and excess survival in the same woman may be observed because of a beneficial environment or selection of healthier women to continue with additional births. Some investigations have made serious efforts to consider the effects of these confounders, but this issue remains a concern in observational studies of human populations. For example, one study using genealogies of the British peerage from 1603 to 1959 found that the relationship between fertility and late-life mortality was obtained only when the influences of health differentials and mortality selection during reproductive ages were taken into account (17
). Another analysis also considered the effects of mortality selection in three natural fertility populations and found that it did not appreciably affect the association between fertility and subsequent survival (18
This body of work has not determined whether improved survival longevity is more likely in the relatives
of late-fertile (or late-menopausal) women, as would be predicted if genes that slow aging also enhance both late fertility in women and longer life spans in both sexes. It is plausible that late female fertility might enhance survival prospects in female relatives, especially in those with no or few children. For most women in natural fertility settings, however, their own reproductive schedules are likely to mask the potentially beneficial influences of having a late-fertile female kin. We are aware of only one study that has considered the association between late female reproduction and longevity among female relatives, but this was found to be insignificant, perhaps a result of the small sample size used (19
). We hypothesize that improved survival is partly attributable to genetic variants that slow the rate of aging in both sexes via a mechanism that also facilitates late female fertility. To test this hypothesis, we compare the survival of men who have a late-fertile sister to men with sisters who were not fertile late. To evaluate the possible role of socioenvironmental factors that may affect this hypothesized association, we examine survival among wives married to brothers of late and non–late-fertile women. This is the first study we are aware of that has considered fraternal longevity as a function of late fertility among female relatives.
This analysis uses brothers to assess familial aggregation of longevity associated with late female fertility for two primary reasons. First, men do not experience the physical challenges associated with pregnancy, childbirth, and their aftermath. Although men are not immune to the influences of their own fertility on their life span (4
), men represent an excellent population to study because the effects of late female (sister) fertility can be examined as a marker for slower aging but without the complications of their own fertility behaviors that are inherent in studies of women. Second, an examination of brothers’ survival as a function of their sister's late fertility focuses the attention on the possibility of shared genetic predisposition for slower aging. This particular sibling-based design (looking at brother's longevity as a function of sister's fertility) is preferred because the putative longevity benefits to women of having a late-fertile sister is complicated by a woman's own fertility history.
If evidence exists for genetic codetermination of late fertility in women and longevity in both sexes, then researchers can select for study the long-lived individuals most likely to carry genes for slower aging, that is, those from families containing late-fertile women. Furthermore, late fertility, along with other biomarkers of slower aging that can be measured in middle-aged women and their family members, may constitute a trait specific for slow aging to allow the identification of the relevant genes even when long-lived research participants are not available.