Stability of DNA-Methylation Profiles of Biological Aging in Children and Adolescents

Abstract

AbstractBackground and ObjectivesMethylation profile scores (MPSs) index biological aging and aging-related disease in adults and are cross-sectionally associated with social determinants of health in childhood. MPSs thus provide an opportunity to trace how aging-related biology responds to environmental changes in early life. Information regarding the stability of MPSs in early life is currently lacking.MethodWe use longitudinal data from children and adolescents ages 8-18 (N = 428, M age = 12.15 years) from the Texas Twin Project. Participants contributed two waves of salivary DNA-methylation data (mean lag = 3.94 years), which were used to construct four MPSs reflecting multi-system physiological decline and mortality risk (PhenoAgeAccel and GrimAgeAccel), pace of biological aging (DunedinPACE), and cognitive function (Epigenetic-g). Furthermore, we exploit variation among participants in whether they were exposed to the COVID-19 pandemic during the course of study participation, in order to test how a historical period characterized by environmental disruption might affect children’s aging-related MPSs.ResultsAll MPSs showed moderate longitudinal stability (test-retestrs = 0.42, 0.44, 0.46, 0.51 for PhenoAgeAccel, GrimAgeAccel, and Epigenetic-g, and DunedinPACE, respectively). No differences in the stability of MPSs were apparent between those whose second assessment took place after the onset of the COVID-19 pandemic vs. those for whom both assessments took place prior to the pandemic.ConclusionsAging-related DNA-methylation patterns are less stable in childhood than has been previously observed in adulthood. Further developmental research on the methylome is necessary to understand which environmental perturbations in childhood impact trajectories of biological aging and when children are most sensitive to those impacts.Article SummaryMethylation profiles of biological aging are less stable in childhood than has been previously observed in adulthood.What’s Known on This SubjectMethylation profile scores (MPSs) index biological aging in adults and are cross-sectionally associated with social determinants of health in childhood. Aging-related MPSs in adulthood show very high test-retest stability but data on longitudinal stability of MPSs in childhood is sparse.What This Study AddsChildren’s methylation profiles of biological aging are moderately stable across an approximately four-year period. Methylation profiles are less stable in childhood than in adulthood, suggesting that aging-related biology in childhood might be more responsive to environmental changes than in adulthood.