Timing of menarche and menopause and epigenetic aging among U.S. adults: results from the National Health and Nutrition Examination Survey 1999-2002

Abstract

Reproductive aging, including timing of menarche and menopause, influences long-term morbidity and mortality in women, yet underlying biological mechanisms remain poorly understood. Using DNA methylation-based biomarkers, we assessed associations of age at menarche (N = 1,033) and menopause (N = 658) with epigenetic aging in a nationally representative sample of women ≥ 50 years. Later age at menopause was associated with lower GrimAge epigenetic age deviation ( $B$ = - 0.10 years, 95% CI: - 0.19, - 0.02). No associations were observed for menarche timing. This suggests a connection between earlier menopause and biological aging, with potential clinical implications for identifying those at high risk for age-related disease.

Keywords: DNA methylation; Epigenetic aging; Menarche; Menopause.

Fig. 1

Adjusted estimates and 95% CI for associations of epigenetic age deviation with age at menarche and age at menopause. Associations were assessed using survey-weighted generalized linear regression models. All models were adjusted for chronological age in years (continuous), chronological age squared, and self-identified race/ethnicity. Estimates are regression coefficients ($B$) that represent the estimated change in each epigenetic age biomarker per one-year increase in age at menarche or age at menopause