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

## TL;DR

This study reviews whether childhood trauma affects biological aging through DNA methylation, finding inconsistent evidence.

## Contribution

A systematic review and meta-analysis of 27 studies on ACEs and DNA methylation age acceleration.

## Key findings

- Meta-analysis found no significant association between cumulative ACEs and first-generation DNA methylation clocks.
- Mixed results for second-generation clocks like PhenoAge and GrimAge, with confidence intervals spanning zero.
- Narrative synthesis highlights methodological heterogeneity and inconsistent findings across individual ACEs.

## Abstract

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.

The online version contains supplementary material available at 10.1186/s13148-025-02047-z.