Early life adversity and age acceleration at mid-life and older ages indexed using the next-generation GrimAge and Pace of Aging epigenetic clocks.

This retrospective cross-sectional study was designed to explore whether the experience of childhood adversity was associated with epigenetic age acceleration in mid-life and older ages using the next generation GrimAge and Pace of Aging DNA methylation clocks. The study involved a sub-sample of 490 individuals aged 50-87 years of age participating in the Irish Longitudinal Study on Aging (TILDA); a large nationally representative prospective cohort study of aging in Ireland. Childhood adversity was ascertained via self-report using 5-items that were deemed to indicate potentially nefarious childhood exposures, including growing up poor, death of a parent, parental substance abuse in the family, childhood physical abuse, and childhood sexual abuse. Only childhood poverty was associated with significant epigenetic age acceleration according to the GrimAge and Pace of Aging clocks, hastening biological aging by 2.04 years [CI= 1.07, 3.00; p < 0.001] and 1.16 years [CI= 0.11, 2.21; p = 0.030] respectively. Analysis of the dose-response pattern revealed each additional adversity was associated with 0.69 years of age acceleration [CI= 0.23, 1.15; p = 0.004] according to the GrimAge clock. Mediation analysis suggested that lifetime smoking explains a substantial portion (>50%) of the excess risk of age acceleration amongst those who experienced childhood poverty. This study adds to the growing body of evidence which implicates early life adversity, particularly deprivation as a potential precipitant of earlier biological aging, and implicates smoking-related changes to DNA methylation processes as a candidate pathway and mechanism through which the social environment gets transduced at a biological level to hasten the aging process.

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