Childhood early life environment associated with GrimAge DNA methylation acceleration in the Health and Retirement Study

BACKGROUND AND AIM[|]Exposure to social and environmental factors throughout childhood and adolescence can alter DNA methylation. Cumulative alterations in DNA methylation are a marker of biologic age. We sought to evaluate the association between three early life exposures and DNA methylation age.[¤]METHOD[|]The Health and Retirement Study is a longitudinal survey of individuals over 50 in the United States. Early life exposures (whether the participant lived in a rural area most of the time as a child, smoked during childhood, and years of schooling) were obtained via questionnaire between 2008 and 2016. DNA methylation in whole blood was measured among 4018 participants in 2016 using the Illumina EPIC array. To estimate DNA methylation acceleration, we used the residuals from regressing GrimAge on chronologic age. We used generalized linear regressions to test for associations between each exposure and accelerated GrimAge, adjusting for age, race/ethnicity, and sex.[¤]RESULTS[|]Participants were on average 69.8 years of age, had 13.3 years of schooling, 59.5% were female, and 72% were non-Hispanic White. Most participants reported not smoking during childhood (81.7%) and not living in a rural area during their childhood (58.4%). Participants who smoked in childhood had 2.72 years (95%CI: 2.34, 3.11) accelerated GrimAge acceleration in later life, relative to those who did not. Additionally, those who spent most of their time in a rural area during childhood had 0.32 years (95%CI: 0.007, 0.63) accelerated GrimAge in later life, relative to those who did not. With each additional year of schooling, participants had 0.295 years (95%CI: -0.352, -0.238) decelerated GrimAge in later life.[¤]CONCLUSIONS[|]We observed childhood residence in rural areas and childhood smoking was associated with accelerated GrimAge DNA methylation. Conversely, we observed that increased schooling was associated with decelerated GrimAge DNA methylation. Conditions in early life may be associated with biologic aging in later life.[¤]