Applying a life course approach to assess the impact of psychosocial stress on allostatic load - Allostatic load, characterized by dysregulation across multiple physiological systems, has been linked to increased risk of chronic diseases such as diabetes, heart disease, and stroke. However, the prevalence of allostatic load varies across segments of the US population, with some groups experiencing a higher burden, particularly during middle and older adulthood. The reasons for these differences are not fully understood, despite research into contributing factors such as diet and socioeconomic conditions. Psychosocial stress has emerged as a key risk factor for allostatic load. While it is understood to operate across multiple contexts—such as interpersonal interactions and neighborhood environments—the combined influence of multiple forms of psychosocial stress on physiological dysregulation remains understudied, as do the biological mechanisms that link these experiences to elevated allostatic load. This study aims to clarify the relationship between multiple forms of psychosocial stress and allostatic load using data from three large, nationally representative cohort studies, in order to inform more effective strategies to reduce physiological wear and tear over the life course. By assessing the associations between interpersonal and neighborhood-level psychosocial stress and allostatic load, the study will quantify how these stressors contribute to physiological burden. The study will also investigate whether the “Conserved Transcriptional Response to Adversity” (CTRA) gene expression profile mediates the relationship between psychosocial stress and allostatic load, and evaluate whether social integration buffers these associations. Overall, this study has the potential to inform the optimization of clinical and place-based interventions aimed at reducing allostatic load by identifying when, where, and for whom such efforts may be most effective.