Neighborhood opportunity and cellular senescence in a national sample of U.S. adults.

While prior research has documented associations between neighborhood conditions and physiological markers of aging, the relationship between neighborhood conditions and cellular aging remains underexplored. We quantified the association between neighborhood opportunity and expression of cellular senescence markers among 1,215 biomarker participants in the Midlife in the United States study. Neighborhood opportunity was assessed using the Childhood Opportunity Index 3.0 (Overall, Education, Health and Environment, Social and Economic Resources). Four transcriptomic markers of cellular senescence were examined from peripheral blood mononuclear cells: CDKN2A RNA abundance, DNA Damage Response (DDR30) composite score, and two Senescence-Associated Secretory Phenotype (SASP10, SASP57) composite scores. After covariate adjustment, individuals living in low-opportunity neighborhoods had significantly elevated CDKN2A RNA abundance (β = 0.32, 95% CI: 0.04, 0.59, p = 0.024) compared to those in high-opportunity neighborhoods. Secondary analysis suggested that this association was potentially driven by low Social and Economic Resources (β = 0.35, 95% CI: 0.07, 0.63, p = 0.013), rather than by Education or Health and Environment domains. No statistically significant relationships were observed for neighborhood opportunity with DDR30, SASP10, and SASP57. These findings provide molecular evidence that low neighborhood opportunity may be biologically embedded at the cellular level. The specificity of associations to social and economic resources and to upstream senescence regulation suggests that neighborhood associations with aging may operate through distinct biological pathways. Future longitudinal studies are needed to establish temporality and explore potential mechanisms linking neighborhood conditions to senescence.