Reproductive behaviors, genetic susceptibility and accelerated aging risk

We examined the associations of reproductive behaviors and genetic susceptibility with aging indicators among female participants in the UK Biobank. Reproductive behaviors included the number of children ever born (NEB), age at first birth (AFB), age at last birth (ALB), and span of years of births (SYB). Aging indicators included frailty, PhenoAge acceleration, KDM-BA acceleration, and brain age difference (BrainAGE-diff). In multivariable analyses, reproductive behaviors showed nonlinear associations with aging indicators. Women with NEB of 2-3 had lower frailty risk, PhenoAge acceleration, KDM-BA acceleration, and BrainAGE-diff. Later AFB and later ALB were also associated with lower levels of several aging indicators, whereas longer SYB was associated with higher frailty risk and PhenoAge acceleration. Mendelian randomization suggested that genetically predicted higher NEB was associated with higher frailty risk and greater PhenoAge acceleration, while genetically predicted later AFB was associated with lower frailty risk and lower PhenoAge and KDM-BA acceleration. Joint analyses showed that high polygenic risk scores combined with NEB > 3, AFB < 25 years, or SYB ≥ 6 years were associated with higher aging burden, although multiplicative interactions were not statistically significant.