Sex differences in aging acceleration: higher susceptibility in women, greater preventability in men

Abstract Aging acceleration contributes to heterogeneity of chronic disease risk and mortality; however, the sex differences of its risk factors and population attributable fractions (PAFs) remain poorly characterized. We conducted an exposure-wide association analysis (ExWAS) among 236,099 UK Biobank participants and examined sex differences in exposure factors of aging acceleration and corresponding PAFs. Our results indicated that environmental exposures, lifestyles, early-life factors, psychosocial factors, and socioeconomic status were all associated with increased risk of accelerated aging. Additionally, several reproductive factors were found to be associated with aging acceleration in women. Notably, women showed higher risk of aging acceleration than men and were more susceptible to adverse lifestyle effects (OR 1.97 [1.91–2.04], PAF = 5.0%), while the potentially preventable proportion was higher in men (OR 1.87 [1.82–1.93], PAF = 16.8%). Collectively, we mapped the risk factor spectrum for accelerated aging and revealed sex differences in aging acceleration, with variation in risk factor effects and corresponding PAFs between sexes.