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The association between adverse childhood experiences and epigenetic age acceleration in the Canadian longitudinal study on aging (CLSA)
Authors:Divya Joshi  Andrea Gonzalez  David Lin  Parminder Raina
Institution:1. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada;2. Labarge Centre for Mobility in Aging, McMaster University, Hamilton, Ontario, Canada

McMaster Institute for Research on Aging, McMaster University, Hamilton, Ontario, Canada

Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada

Offord Centre for Child Studies, Hamilton, Ontario, Canada;3. Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada

Abstract:Research examining the association between exposure to a wide range of adverse childhood experiences (ACEs) and accelerated biological aging in older adults is limited. The purpose of this study was to examine the association of ACEs, both as a cumulative score and individual forms of adversity, with epigenetic age acceleration assessed using the DNA methylation (DNAm) GrimAge and DNAm PhenoAge epigenetic clocks in middle and older-aged adults. This cross-sectional study analyzed baseline and first follow-up data on 1445 participants aged 45–85 years from the Canadian Longitudinal Study on Aging (CLSA) who provided blood samples for DNAm analysis. ACEs were assessed using a validated self-reported questionnaire. Epigenetic age acceleration was estimated by regressing each epigenetic clock estimate on chronological age. Cumulative ACEs score was associated with higher DNAm GrimAge acceleration (β: 0.07; 95% CI: 0.02, 0.11) after adjusting for covariates. Childhood exposure to parental separation or divorce (β: 0.06; 95% CI: 0.00, 0.11) and emotional abuse (β: 0.06; 95% CI: 0.00, 0.12) were associated with higher DNAm GrimAge acceleration after adjusting for other adversities and covariates. There was no statistical association between ACEs and DNAm PhenoAge acceleration. Early life adversity may become biologically embedded and lead to premature biological aging, in relation to DNAm GrimAge, which estimates risk of mortality. Strategies that increase awareness of ACEs and promote healthy child development are needed to prevent ACEs.
Keywords:adverse childhood experiences  CLSA  epigenetic age acceleration  GrimAge  PhenoAge
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