Objective:To explore the mediating effect of unhealthy lifestyle and depressive symptom on the associations between life course factors and aging health.Methods:The study included 6 217 participants (aged ≥45 years) from the China Health and Retirement Longitudinal Study (CHARLS). We used principal component analysis (PCA) and hierarchical clustering analysis (HCA) to divide participants into six subgroups based on 70 life course factors. Five key life course factors were identified based on correlation analysis and their contribution to aging health. Physiological dysregulation (PD) was calculated by using eight biomarkers in the 2015 CHARLS biomarker dataset. Linear regression, logistic regression, and mediation models were used to explore the complex associations of life course subgroups, key factors, unhealthy lifestyle, depression symptom with PD.Results:Life course subgroups were significantly associated with PD after adjusting chronological age and gender ( β: 0.08-0.17, all P<0.05). Life-course subgroups and key factors, including adverse experiences in adulthood and lower education level, were significantly associated with unhealthy lifestyle ( β: 0.04-0.52, all P<0.05). Life-course subgroups and key factors, including childhood trauma, parental health in childhood, adverse experiences in adulthood, and lower education level, were significantly associated with depression symptom ( OR: 1.16-4.76, all P<0.05). Mediation analysis showed that unhealthy lifestyle had partial mediating effect on the association of life course subgroups and key factors, including adverse experiences in adulthood, and lower education levels, with PD (3.1%-3.6%). Depression symptom had partial mediating effect on the association of life course subgroups and key factors, including childhood trauma, adverse experience in adulthood, and lower education level, with PD (6.0%-16.2%). Conclusions:Unhealthy lifestyle and depression symptom has partial mediating effect on the impact of life course factors on aging health. It is important to pay attention to these two modifiable factors while targeting childhood trauma and adverse experience in adulthood.