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Historic redlining and accelerated biological aging in U.S. urban adolescents Sarah Laurent* Sarah Laurent Helen C.S. Meier Lorraine Halinka Malcoe

Background: Historic redlining has shaped present-day neighborhoods, inequitably exposing residents of formerly redlined regions to harmful conditions and stressors. Neighborhood disadvantage can accelerate biological aging measured via DNA methylation epigenetic clocks.

Objective: We examined the association between historic redlining and epigenetic accelerated aging in adolescents.

Methods: Data come from the Future of Families and Child Wellbeing Study. A total of 1,686 adolescents provided saliva samples used to derive DNA methylation accelerated aging (DNAmAA). Historic redlining scores assessed the proportion of census tracts graded by the Home Owners’ Loan Corporation (HOLC) “residential security” maps from the early 20th century multiplied by a weighted HOLC grade. Census tracts were categorized as “high” or “low” redlining; areas minimally assessed by HOLC were marked as “ungraded”. We used linear regression models to examine the association between redlining categories and DNAmAA using 8 epigenetic clocks, adjusting for age, baseline city, assay type, cell proportion, mother’s smoking during pregnancy and household poverty ratio.

Results: Residence in high redlining tracts was strongly racialized (p<0.001): 35.1% of Hispanic and 45.3% of non-Hispanic Black adolescents lived in high redlining tracts versus 12.7% of non-Hispanic whites. After adjusting for covariates, adolescents living in high redlining tracts had greater DNAmAA compared to those living in ungraded regions among the GrimAge (p<0.001), Horvath (p=0.008), PhenoAge (p=0.019) and Skin/Blood clocks (p=0.022). Sub-sample analyses examining non-Hispanic Black and Hispanic participants alone showed no significant associations.

Discussion: This study is the first to show how historic redlining may become biologically embedded in adolescents living in U.S. urban areas. Findings suggest that historic structural racism drives present-day health inequalities in adolescents via accelerated biological aging.