Late reproduction is associated with extended female survival but not with familial longevity

Abstract Objective Female reproductive health comprises adequate oocyte quality and quantity, normal fecundability, a normal course of pregnancy, and the delivery of healthy offspring. General aging patterns and the maintenance of somatic health have been associated with female reproductive health. However, it is unknown whether better long-term somatic maintenance is directly related to reproductive outcomes, and whether there is a shared genetic predisposition underlying both somatic and reproductive aging. Here we investigate whether reproductive health is related to female lifespan or familial longevity. Design Observational study Subjects 10,255 female members of a multigenerational historical cohort (1812-1910), the LINKing System for historical family reconstruction (LINKS) and 1,258 females from 651 long-lived families in the Leiden Longevity Study. Main outcome measures The association between reproductive characteristics and longevity was studied both on an individual and familial level. Individual survival was studied in relation to age at last childbirth and total number of children. Familial longevity was studied through parental survival and related to age at last childbirth, total number of children and a polygenic risk score (PRS) for age at menopause. Results Females giving birth to their last child at a higher age lived longer: for each year increase in the age of the birth of the last child, a woman’s lifespan increased with 0.06 years (22 days) (p<0.005). Females who lived to be in the top 10% survivors of their birth cohort (n=2,241, 21.9%) on average gave birth to their last child at a 1% later age than the remaining cohort (IRR=1.01, p<0.005). Females with 1 or 2 long-lived parents did not have a higher mean age of last childbirth. There was neither a significant association between an increasing number of long-lived ancestral family members (familial longevity), nor the PRS. Conclusion Female reproductive health associates with a longer lifespan and with survival to more extreme ages (longevity). The heritable component in familial longevity, however, does not associate to extended reproductive health and the PRS underlying age at menopause does not explain familial longevity. Other factors in somatic maintenance that support a longer lifespan are likely to have an impact on reproductive health.