Depression and biological aging: Unexpected vulnerability in relatively advantaged social risk profile group

BACKGROUND: Depression has significantly associated with biological aging. Although lower social status is generally linked to increased vulnerability to aging, the biological impact of depression may differ according to social status, possibly due to variations in stress perception and structural position. However, it remains unclear how depression is related to biological age acceleration across different social risk profile (SRP). METHODS: We analyzed 18,787 participants from NHANES 2005-2020. PhenoAgeAccel was used as a validated biomarker of biological aging. Depression was defined as PHQ-9 ≥ 10. SRP was categorized into four strata according eight socioeconomic indicators. Survey-weighted linear regression models analyzed the relationship between depression and PhenoAgeAccel, controlling for demographic and health-related covariates. Further SRP subgroups were conducted to investigate the correlation between depression and PhenoAgeAccel. The robustness was assessed with models that include SRP as a continuous variable together with all eight SRP components. Demographic subgroup analyses were performed to assess heterogeneity in these associations, applying Benjamini-Hochberg false discovery rate (BH-FDR) correction. RESULTS: Depression exhibited an independent correlated with PhenoAgeAccel. A more robust association was observed in High SRP (β = 0.96, 95% CI: 0.11-1.82) and Lower-middle SRP (β = 0.39, 95% CI: 0.01-0.77), but not in Low SRP. Subgroup analyses revealed a statistically significant association among White individuals in the High SRP group. CONCLUSION: Depression was associated with accelerated biological aging, especially among relatively advantaged SRP groups, alongside evidence of heterogeneity across racial groups. These suggested that social advantage may not mitigate the biological consequences of psychological suffering. Addressing aging disparities requires enhanced integration of mental health interventions with structural support.