The impact of adverse childhood experiences on DNA methylation age: a systematic review and meta-analysis

Jan 24, 2026Clinical epigenetics

How difficult childhood experiences are linked to changes in biological aging of DNA

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Abstract

A systematic review of 27 observational studies involving 1,036 participants found no significant associations between adverse childhood experiences (ACEs) and epigenetic age acceleration (EAA).

Cumulative exposure to ACEs may influence biological aging, but current evidence does not show a robust association with EAA.
Meta-analyses of six studies using first- and second-generation epigenetic clocks revealed standardized regression coefficients indicating no significant effects.
Most studies included more female participants, with a median of 56.6%, and used various epigenetic clocks, predominantly Horvath, GrimAge, and PhenoAge.
Many studies had concerns regarding risk of bias, primarily due to inadequate adjustment for important variables.
Narrative synthesis highlighted methodological inconsistencies and mixed findings, particularly with individual ACEs and advanced epigenetic clocks like DunedinPACE.

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Adverse childhood experiences (ACEs), such as abuse and neglect, are associated with poor health in adulthood. One proposed biological mechanism linking early adversity to health outcomes is epigenetic age acceleration (EAA), a measure of biological aging derived from DNA methylation. Understanding whether ACEs contribute to EAA might identify pathways linking early life stress to increased risk of morbidity and mortality.This systematic review and meta-analysis examined the relationship between cumulative ACE exposure and EAA in adults across 27 eligible observational studies from 1036 identified by comprehensive screening of the literature. Studies involved more female participants (median 56.6%) and employed a range of epigenetic clocks, most frequently Horvath, GrimAge, and PhenoAge. Risk of bias was assessed using the ROBINS-E tool, with most studies rated as having some concerns, primarily due to a lack of adjustment for key covariates. Meta-analyses of 6 studies using cumulative ACE exposure and standardised regression coefficients revealed no significant associations with EAA for first-generation clocks (Horvath: β = - 0.03, 95% CI - 0.15 to 0.09; Hannum: β = - 0.09, 95% CI - 0.41 to 0.23) or second-generation clocks (PhenoAge and GrimAge: both β = 0.21, 95% CIs spanning zero). Narrative synthesis of studies, including those that could not be considered in the meta-analyses, highlighted heterogeneous methodologies and mixed findings, particularly for individual ACEs and third generation clocks such as DunedinPACE. These findings suggest that while ACEs may influence biological aging, current evidence does not support a robust or consistent association with EAA. The study identifies the need for more consistent methodologies in future research.

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The impact of adverse childhood experiences on DNA methylation age: a systematic review and meta-analysis

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