Mechanisms of ageing and developmentSep 14, 2026

Biological Age from DNA Methylation and Its Relationship to Reproductive History: Review and Combined Analysis

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 15, 2026

Abstract

A total of 550,550 participants were analyzed, revealing that preterm birth and earlier age at menopause are associated with higher epigenetic age acceleration.

Each one-year earlier age at menopause is significantly linked to an increase in epigenetic age acceleration, particularly measured by GrimAge.
Meta-analysis indicates that higher age at menopause correlates with lower epigenetic age acceleration.
Parity is associated with epigenetic age acceleration, with an increase of 0.13 years for each additional delivery according to PhenoAge.
No consistent relationship between age at menarche and epigenetic age acceleration was observed across any DNA methylation clocks.
Findings suggest that specific aspects of reproductive history may influence biological aging as indicated by DNA methylation clocks.

Simplified

Reproductive history has implications for long-term health, with menopausal timing and parity associated with chronic disease risk. DNA methylation (DNAm) clocks are biomarkers of aging and estimate epigenetic age acceleration (EAA) in reproductive tissues and systemically. DNAm clocks provide mechanistic insight into how reproductive history relates to aging. This study aimed to identify associations between reproductive history and DNAm clocks. Twenty-nine studies comprising 550,550 participants (median mean age=35.4 (IQR: 30.3-62.7) years, 100% female) assessing associations between reproductive history and EAA were included. Across studies, preterm birth and earlier age at menopause was consistently associated with higher EAA, yet age at menarche, pregnancy complications, and adverse birth outcomes showed mixed findings. Meta-analysis of cross-sectional studies showed each one-year earlier age at menopause was significantly associated with higher EAA, strongest in GrimAge (n=5920, β=-0.08 years, 95% CI: -0.11, -0.05). No relationship was found between age at menarche and EAA in any DNAm clocks. Meta-analysis of parity showed associations with EAA using PhenoAge (n=4508, β=0.13 years per delivery, 95% CI: 0.04, 0.21). These findings highlight that aspects of reproductive history are cross-sectionally associated with higher EAA, particularly measured with 2^nd generation DNAm clocks (PhenoAge, GrimAge).

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Biological Age from DNA Methylation and Its Relationship to Reproductive History: Review and Combined Analysis

Abstract

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