How does life course exposure to contextual disadvantage accelerate biological aging? The role of psychological symptoms.

<h4>Objectives</h4>Recent research has found that life course exposure to contextual socioeconomic disadvantage may accelerate biological aging, providing key insight into an upstream driver of health disparities. However, questions about the intervening mechanisms remain. We examine the role of psychological symptoms in the direct and indirect relationships between cumulative neighborhood disadvantage and accelerated biological aging.<h4>Methods</h4>We leverage the Researching Epigenetic, Weathering, Aging, & Neighborhood Disadvantage (REWARD) Study, a subsample of the Survey of the Health of Wisconsin (SHOW) (2008-2019) that includes an assessment of cumulative neighborhood disadvantage based on long-term residential histories and three blood-based epigenetic clocks (i.e., GrimAge, PhenoAge, and DunedinPACE). We use path analysis to assess the direct and indirect relationship of cumulative neighborhood disadvantage and accelerated biological aging through psychological symptoms measured as overall distress and disaggregated as depression, anxiety, and stress symptoms.<h4>Results</h4>Cumulative neighborhood disadvantage is associated with epigenetic age acceleration directly and indirectly via overall psychological distress, with 10-13% of the neighborhood disadvantage effects mediated by increased distress across the aging clocks. Anxiety appears as a significant mediating factor for some clocks (most notably GrimAge and DunedinPACE).<h4>Discussion</h4>Contextual disadvantage is an important social determinant of health that operates throughout the life course and may lead to disparities in healthy aging through psychological symptoms.