Childhood Maltreatment and Longitudinal Epigenetic Aging: NIMHD Social Epigenomics Program.

Importance: Child physical and emotional abuse and neglect may affect epigenetic signatures of accelerated aging several years after the exposure. Objective: To examine the longitudinal outcomes of early-childhood and midchildhood exposures to maltreatment on later childhood and adolescent profiles of epigenetic accelerated aging. Design, Setting, and Participants: This cohort study used data from the Future of Families and Child Wellbeing Study (enrolled 1998-2000), a US birth cohort study with available DNA methylation (DNAm) data at ages 9 and 15 years (assayed between 2017 and 2020) and phenotypic data at birth (wave 1), and ages 3 (wave 3), 5 (wave 4), 9 (wave 5), and 15 (wave 6) years. Data were analyzed between June 18 and December 10, 2023. Exposures: Emotional aggression, physical assault, emotional neglect, and physical neglect via the Parent-Child Conflict Tactics Scale at ages 3 and 5 years. Main Outcomes and Measures: Epigenetic accelerated aging (DNAmAA) was measured using 3 machine learning-derived surrogates of aging (GrimAge, PhenoAge, and DunedinPACE) and 2 machine learning-derived surrogates of age (Horvath and PedBE), residualized for age in months. Results: A total of 1971 children (992 [50.3%] male) representative of births in large US cities between 1998 and 2000 were included. Physical assault at age 3 years was positively associated with DNAmAA for PhenoAge (β = 0.073; 95% CI, 0.019-0.127), and emotional aggression at age 3 years was negatively associated with PhenoAge DNAmAA (β = -0.107; 95% CI, -0.162 to -0.052). Emotional neglect at age 5 years was positively associated with PhenoAge DNAmAA (β = 0.051; 95% CI, 0.006-0.097). Cumulative exposure to physical assault between ages 3 and 5 years was positively associated with PhenoAge DNAmAA (β = 0.063; 95% CI, 0.003-0.123); emotional aggression was negatively associated with PhenoAge DNAmAA (β = -0.104; 95% CI, -0.165 to -0.043). The association of these measures with age 15 years PhenoAge DNAmAA was almost fully mediated by age 9 years PhenoAge DNAm age acceleration. Similar patterns were found for GrimAge, DunedinPACE, and PhenoAge, but only those for PhenoAge remained after adjustments for multiple comparisons. Conclusions and Relevance: In this cohort study, altered patterns of DNAmAA were sensitive to the type and timing of child maltreatment exposure and appeared to be associated with more proximate biological embedding of stress.