A Systematic Review of Adverse Childhood Experiences and Epigenetic Age Acceleration in Later Adult Life Measured With Second and Third-Generation Epigenetic Clocks

We examined the relationship between adverse childhood experiences (ACEs) and epigenetic age acceleration (EAA) in adulthood as measured by second and third generation epigenetic clocks by performing a systematic review of the literature. The electronic databases MEDLINE and EMBASE were searched on 17 July 2023. All studies measuring epigenetic age using the second and third-generation clocks in adults who experienced ACEs when under the age of 18 were included. Papers from before 1 January 2018, papers where the full text was not available in the English language, and animal studies were excluded. Two independent reviewers extracted the data and screened the studies against the defined eligibility criteria, and any discrepancies were resolved by referral to an independent third reviewer. The Crowe Critical Appraisal Tool was used to assess bias. The outcome of interest was epigenetic age acceleration measured by second and third generation epigenetic clocks. Eight hundred thirty-six studies were identified by the search strategy. Ten studies were ultimately included in the review, nine of which were either high quality or very high quality. A consistent positive association between ACEs and EAA was seen across the studies with evidence of a dose-response effect. This study suggests that previously reported observations of childhood trauma leading to poorer adult health could be mediated by epigenetic changes to DNA among European populations. Further studies are needed to see if these findings are replicated in other ethnic groups.