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

Hannah Russell; Gregor Angus; Sam Singleton; Christopher G. Bell; Tim G Hales

doi:10.1186/s13148-025-02047-z

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

Hannah Russell
, Gregor Angus
, Sam Singleton
, Christopher G. Bell
, Tim G Hales (Lead / Corresponding author)

Neuroscience

Research output: Contribution to journal › Article › peer-review

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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 1,036 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.

Original language	English
Article number	33
Journal	Clinical Epigenetics
Volume	18
Issue number	1
Early online date	24 Jan 2026
DOIs	https://doi.org/10.1186/s13148-025-02047-z
Publication status	Published - 17 Feb 2026

Keywords

Trauma
neglect
biological age
epigenetic clock
Epigenetic clock
Neglect
Biological age

ASJC Scopus subject areas

Molecular Biology
Genetics
Developmental Biology
Genetics(clinical)

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10.1186/s13148-025-02047-zLicence: CC BY

Final published version
The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder
Final published version, 1.95 MBLicence: CC BY

Cite this

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title = "The impact of adverse childhood experiences on DNA methylation age: A systematic review and meta-analysis",

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 1,036 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.",

keywords = "Trauma, neglect, biological age, epigenetic clock, Epigenetic clock, Neglect, Biological age",

author = "Hannah Russell and Gregor Angus and Sam Singleton and Bell, \{Christopher G.\} and Hales, \{Tim G\}",

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AU - Bell, Christopher G.

AU - Hales, Tim G

N1 - Publisher Copyright: © The Author(s) 2026.

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Y1 - 2026/2/17

N2 - 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 1,036 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.

AB - 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 1,036 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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JO - Clinical Epigenetics

JF - Clinical Epigenetics

IS - 1

M1 - 33

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

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Consortium Against Pain InEquality (CAPE) - The Impact of Adverse Childhood Experiences on Chronic Pain and Responses to Treatment (Joint with University of Aberdeen, University of Edinburgh, University of Stirling and University College, London) (Advanced Pain Discovery Platform)

Cite this

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

Consortium Against Pain InEquality (CAPE) - The Impact of Adverse Childhood Experiences on Chronic Pain and Responses to Treatment (Joint with University of Aberdeen, University of Edinburgh, University of Stirling and University College, London) (Advanced Pain Discovery Platform)

Cite this