Food insecurity, epigenetic age acceleration, and depression in middle-aged and older adults: a longitudinal cohort study.

Abstract

Depression in middle-aged and older adults is a major contributor to disability, yet upstream social adversity remains underrecognized in prevention. We assessed whether food insecurity (FI) was associated with incident depression and depressive-symptom burden in the US Health and Retirement Study, and whether epigenetic age acceleration (EAA) mediated this association. FI was measured using the six-item US Department of Agriculture Food Security Survey Module. Depressive symptoms were assessed with the eight-item Center for Epidemiologic Studies Depression Scale (CES-D-8), with incident depression defined as elevated depressive symptoms using the ≥3 threshold. Associations between FI and incident depression were estimated using multivariable Cox models, and symptom trajectories were analyzed using mixed-effects models. In an epigenetic subsample ( n = 1,430), 13 DNA methylation clocks were profiled. EAA was derived as age-adjusted residuals and its mediating role was assessed. Among 5,547 participants included, 1,320 developed incident depression over 7.9 years. Compared with high food security, low and very low food security were associated with higher hazards [hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.32-1.88; and HR 1.94, 95% CI 1.58-2.37], with evidence of a non-linear dose-response and an estimated 9% of incident cases attributable to FI. FI was also associated with a higher depressive-symptom burden (β = 0.72 and 1.59; both P < 0.001). Zhang AgeAccel accounted for a small proportion of this association, explaining 5.3% of the total effect. Food insecurity was associated with higher depression risk and sustained depressive-symptom burden in middle-aged and older adults. EAA accounted for a small proportion of this association.