DNA methylation clocks and reproductive history: systematic review and meta-analysis
In this abstract of a systematic review and meta-analysis of 29 studies in 550,550 female participants, earlier menopause and preterm birth were consistently linked to higher epigenetic age acceleration; age at menarche showed no such link. These are cross-sectional associations, not causes. [1]
Automatic summary · not editorially reviewed
The key findings
The review included 29 studies with 550,550 participants, all female, median mean age 35.4 years. [1]
Preterm birth and earlier menopause were consistently associated with higher epigenetic age acceleration, while age at menarche, pregnancy complications and adverse birth outcomes showed mixed findings. [1]
In cross-sectional meta-analysis, each one year earlier at menopause was associated with higher EAA, strongest for GrimAge, and PhenoAge showed an association with parity. [1]
The source at a glance
- Study type / format
- Systematic review and meta-analysis of cross-sectional studies (abstract).
- Population / context
- 550,550 female participants in 29 studies (median mean age 35.4 years).
- Summary based on
- Study abstract
- Original publication
- September 14, 2026
Reproductive history and epigenetic age in 550,550 women
The review asked whether reproductive history is associated with DNA methylation clocks, which are biomarkers of aging that estimate epigenetic age acceleration (EAA). It included 29 studies with 550,550 participants, all female, with a median mean age of 35.4 years (interquartile range 30.3–62.7). The authors describe menopausal timing and parity as linked to chronic disease risk and present the clocks as a way to study how reproductive history relates to aging.
Supporting source [1]
Earlier menopause and preterm birth linked to higher EAA
Across the studies, preterm birth and an earlier age at menopause were consistently associated with higher EAA. Age at menarche, pregnancy complications and adverse birth outcomes showed mixed findings. In the meta-analysis of cross-sectional studies, each one year earlier at menopause was significantly associated with higher EAA, strongest for GrimAge (n = 5,920; β = −0.08 years; 95% CI −0.11 to −0.05). No relationship was found between age at menarche and EAA in any clock. For parity, PhenoAge showed an association (n = 4,508; β = 0.13 years per delivery; 95% CI 0.04 to 0.21).
Supporting source [1]
Cross-sectional links, strongest with second-generation clocks
The authors conclude that aspects of reproductive history are cross-sectionally associated with higher EAA, particularly when measured with second-generation DNA methylation clocks (PhenoAge, GrimAge). Because the meta-analysed studies were cross-sectional, the results describe associations at one point in time and do not show that reproductive events cause changes in epigenetic age. This information comes from the abstract only; the full text was not reviewed.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. The meta-analysed studies were cross-sectional, so associations do not establish causation. Findings for age at menarche, pregnancy complications and adverse birth outcomes were mixed.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Simonson MW, Wang W, Tay JH, Hameed S, Min CH, Khan A, Reji A, Maier AB. · europepmc.org · September 14, 2026