Childhood trauma, accelerated biological aging and chronic pain across two population cohorts

Background Adverse childhood experiences are associated with reduced healthy longevity, multimorbidity, and chronic pain, but the biological mechanisms involved remain poorly understood. Epigenetic age acceleration (EAA), a DNA methylation marker of biological aging, may represent a pathway through which early-life stress becomes embedded. We therefore examined associations between childhood trauma (CT), EAA and chronic pain, and investigated whether accelerated biological aging mediates the relationship between CT and chronic pain in women and men. Methods We analysed two independent population cohorts from the UK and USA: Generation Scotland (n = 901) and MIDUS (n = 1041). EAA was derived from first-generation (Hannum and Horvath) and second-generation (GrimAge and PhenoAge) DNA methylation clocks relative to chronological age. DunedinPACE, a third-generation measure, was used to estimate pace of aging. Associations between CT, EAA and chronic pain were examined using sex-stratified regression models adjusted for confounders and covariates, followed by mediation analyses. Findings CT was associated with chronic pain and with accelerated biological aging measured primarily using second- and third-generation clocks. Associations were consistently stronger in women, and smoking-related methylation contributed substantially to the relationship between EAA and chronic pain. Mediation analyses revealed that EAA partially accounts for the link between CT and chronic pain in women. Interpretation Second- and third-generation clocks appeared more sensitive to the long-term consequences of childhood trauma than clocks trained primarily on chronological age. The findings suggest that CT contributes to chronic pain vulnerability partly through accelerated biological aging pathways, particularly in women.