PROJECT SUMMARY/ABSTRACT Although research linking race-based residential segregation to health outcomes has been conducted for decades, there is currently a lack of understanding of how exposure to residential segregation affects the universal aging process that underlies development of chronic disease. Our long-term goal is to understand how a fundamental cause of racial health disparities, residential segregation, leads to physiologic dysregulation through examination of modifiable causal pathways. The overall objectives of this application are (i) to measure the association between residential segregation and age acceleration over the adult life course; and (ii) identify the mechanisms through which living in a segregated neighborhood affects age acceleration. The central hypothesis is that exposure to residential segregation over the adult life course is associated with worse (higher) clinical marker-derived age acceleration, a marker of stress-related cumulative physiological dysregulation. The rationale for this project is that our findings may strengthen the evidence base for policy recommendations by demonstrating that structural factors harm the universal aging process, making equity important for all of society. The central hypothesis will be tested by pursuing three specific aims: 1) Determine the relationship of exposure to levels of residential segregation and age acceleration in adulthood in Black CARDIA participants; 2) Identify neighborhood-level mediators of the relationship between residential segregation and age acceleration; and 3) Using a life-course lens, determine if timing and length of exposure to residential segregation affects its relationship with age acceleration. For the first aim mixed effects growth models and parallel process growth models will be used to measure the relationship between residential segregation and age acceleration. The second aim will use structural equation modeling to determine if neighborhood SDOH mediates the influence of living in residentially segregated neighborhoods and increased age acceleration. The third aim will use path analysis to test the pathways hypothesized through each life course model. The research proposed is innovative because 1) it will be the first attempt to link structural factors to our novel measure of accelerated biological aging, and 2) it focuses on untangling how residential segregation works to harm health over the adult life course. The proposed research is significant because research shows structural racism and its downstream consequences, termed the social determinants of health (SDOH), produce racial disparities in health outcomes but far less work has examined how structural racism affects the aging process that is the basis for many chronic diseases (e.g., cardiovascular diseases, diabetes, hypertension, stroke). Even less work has examined how the timing of exposure to structural and social determinants of health (S/SDOH) during the life course affects a...