Effects of Accelerated Biological Age on Depressive Symptoms in a Causal Reasoning Framework.

BACKGROUND:Depression in middle-aged and elderly individuals is multifaceted and heterogeneous, linked to biological age (BA) based on aging-related biomarkers. However, due to confounding with chronological age and the absence of subgroup analysis and causal reasoning, the association between BA and depressive symptoms (DS) might be unstable and requires further investigation.METHODS:We utilized data from the China Health and Retirement Longitudinal Study (N = 9478) to perform association analysis, causal inference, and subgroup analysis. BA acceleration (BAA) was derived using machine learning and adjusted for chronological age. A generalized linear mixed-effects model (GLMM) tree algorithm was employed to identify subgroups. The causal reasoning frame included propensity score matching and fast large-scale almost matching exactly.RESULTS:In the longitudinal analysis, BAA exhibited a consistent and significant positive association with DS, even after controlling for demographic characteristics, lifestyle factors, health status, and physical functions. This association remained unchanged within the causal framework. GLMM tree analysis identified three partitioning variables (sex, satisfaction, and BMI) and five subgroups. Further subgroup analysis revealed that BAA exerted the strongest effect on DS among women with less satisfying lives.LIMITATIONS:Depressive symptoms were evaluated through scale measurements rather than clinical diagnosis. The sample was derived from the general population, not the clinically depressed population.CONCLUSIONS:This study provided the first longitudinal evidence that biological age acceleration increases depressive symptoms under causal reasoning and subgroup analysis, particularly among less satisfied women. And the association between BAA and DS was independent of known risk factors.