PROJECT SUMMARY/ABSTRACT Intersecting structural conditions, including racism and other systems of oppression create structural adversity that impacts health and life expectancy, especially for Black Americans and other racialized communities. The proposed mixed-methods research will collect new data to complement a wealth of existing longitudinal data previously collected at key developmental stages over more than three decades from two ethnically, racially, and socioeconomically diverse cohorts from the Harlem Longitudinal Development Study and the Children in the Community Study. The sample will consist of 450 Black, Latinx and white adults previously surveyed in childhood/early adolescence, emerging adulthood, young adulthood, and midlife. The proposed research, informed by the Phenomenological Variant of Ecological Systems Theory, will quantify and contextualize the assocations of exposure to structural adversity, namely individual-level life-course experiences of adversity within and across institutions and social contexts over the life course (e.g., stigma/discrimination, socioeconomic disadvantage) and neighborhood-level ethnic-racial inequality with stress regulation, epigenetic modifications (i.e., epigentic age), and mental health (i.e., psychological distress, depression, anxiety, posttraumatic stress, race-based traumatic stress). This will be accomplished using four forms of data that will be triangulated to optimize results and interpretation: survey, biological, qualitative, and U.S. Census data. The proposed research will also include innovative development and validation of a new Intersectional Stigma in Context tool (ISIC) that will be compared and contrasted with existing stigma/discrimination measures. The quantitative survey and biological data will facilitate comprehensive analysis of racialized differences in structural adversity and its association with stress regulation, epigenetic aging, and mental health. These analyses will be further contextualized through in-depth interviews with a purposive sample selected from the study cohort. The qualitative data will innovatively provide deeper understanding and interpretation of structural adversity over the life course, including stigma/discrimination, stress, resilience, and other salient experiences that are often missed by quantitative data, including contexualized information of past generations. Further, this research will identify protective factors that can mitigate the deleterious sequelae of adversity and thus highlight areas of resilience that can be leveraged in interventions. In conclusion, identifying how racism and intersecting systems of oppression permeate and reproduce social conditions that manifest at the individual and neighborhood levels – creating structural adversity – will be examined for it’s association with biological stress regulation, epigenetic aging, and mental health. This will constitute a crucial step towards changing policies and systems tha...