Evidence for the causal relationship between age at first sexual intercourse and multidimensional aging phenotypes from a full life cycle perspective: A mendelian randomization study

The full life cycle perspective emphasizes the profound impact of early-life events on later health. Age at first sexual intercourse (AFS) marks the onset of an individual’s sexual development and behavior, which may influence the aging trajectory. This study aims to investigate the causal effects of AFS on multidimensional aging phenotypes and identify potential mediating mechanisms from a full life cycle perspective. Mendelian Randomization (MR) analysis. This study employed two-sample MR analysis, using genetic instruments for AFS to estimate its causal effects on various aging phenotypes, including aging-genetically independent phenotypes (aging-GIP), longevity, frailty index, parental lifespan, healthspan, and self-rated health. Subsequently, a two-step MR mediation analysis was conducted to determine the mediating effects between AFS and aging-GIP. Earlier AFS was causally associated with lower aging-GIP ( β , 0.42; 95%CI, 0.36–0.48). Similar association patterns were observed for longevity ( OR , 1.41; 95%CI, 1.11–1.78) and parental lifespan ( β , 0.33; 95%CI, 0.28–0.39), while negative causal relationships were found with frailty index ( β , −0.30; 95%CI, −0.36 to −0.25), healthspan ( β , −0.26; 95%CI, −0.33 to −0.18), and self-rated health ( β , −0.32; 95%CI, −0.37 to −0.26). Mediation analysis identified 34 exploratory mediators among 145 candidate mediators between AFS and aging-GIP. The findings underscore the importance of early sexual health education and suggest implementing targeted interventions to mitigate the adverse effects of early sexual behavior on aging. This approach can promote healthy aging and reduce aging disparities caused by early sexual initiation.