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Abstract Importance Adverse neighborhood conditions can lead to poorer health outcomes, potentially through accelerated biological aging. However, whether these relationships are explained by individual- or neighborhood-level factors remains unclear. Objective To examine the association between neighborhood deprivation, measured by the Area Deprivation Index (ADI), and epigenetic age acceleration and assess whether individual- and neighborhood-level characteristics mediate or modify these associations. Design Cross-sectional study using data from a Yale Stress Center study between 2008 and 2012. Data analysis was conducted from July 2025 to January 2026. Setting Community-based sample from the greater New Haven, CT area. Participants A total of 370 healthy adults aged 18 to 50 years without major psychiatric, medical, or cognitive disorders who provided blood samples for DNA methylation analysis. Main Outcomes and Measures Epigenetic age acceleration measured from DNA methylation using four second-generation epigenetic clocks, with associations assessed among aging, neighborhood deprivation, and individual- and neighborhood-level factors. Results Data were analyzed from 370 participants (212 women 57.3%, 158 men 42.7%; mean SEM age, 29.3 0.46 years). Greater neighborhood deprivation was associated with greater lifetime adversity (β=0.112, p<.001) and lower educational attainment (β=-0.019, p=.012), and accelerated epigenetic aging as measured by GrimAge (β=0.037, p<.001), PCGrimAge (β=0.019, p<.001), and PCPhenoAge (β=0.041, p<.001), but not PhenoAge (p=.23). In multivariable models accounting for individual factors, neighborhood deprivation remained associated with these three clocks. Lifetime adversity partially mediated the association between ADI and accelerated GrimAge (20.3% of total effect) and PCGrimAge (23.3%). Race moderated the direct association between ADI and epigenetic aging, with stronger associations between neighborhood deprivation and accelerated GrimAge (β=0.061, p=.004) and PCPhenoAge (β=0.057, p=.02) observed among Black participants compared to White. Conclusions Greater neighborhood deprivation was associated with accelerated epigenetic aging across multiple second-generation clocks, with lifetime adversity partially mediating these associations. Stronger effects were observed among Black participants. These findings suggest that neighborhood environments and cumulative stress may contribute to biological aging and racial disparities in aging trajectories. Key Points Question Is neighborhood deprivation associated with epigenetic age acceleration, and if so, how do neighborhood- and individual-level factors impact this relationship? Findings In this cross-sectional study of 370 adults, greater neighborhood deprivation was associated with accelerated epigenetic aging across multiple second-generation clocks. Lifetime adversity partially mediated these associations, and the relationship between neighborhood deprivation and accelerated aging was stronger among Black participants than White participants. Meaning These findings suggest that neighborhood conditions and lifetime stress contribute to accelerated biological aging and suggest that epigenetic aging may represent one biological pathway through which neighborhood-level racial inequalities contribute to health disparities.
Koirala et al. (Mon,) studied this question.