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

ABSTRACT

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.