Extended Data Fig. 8: Organismal and brain aging in mental well-being and psychiatric diseases.

a, Associations of brain and peripheral organ (kidney, intestine, and pancreas) aging (age gaps) with PHQ-4 score and depressive and anxiety symptoms at baseline in participants without neurodegenerative and psychiatric diseases (n = 37,764). Associations were estimated by linear regression, presented as beta coefficients. b, Associations of brain and peripheral organ aging with future mental health conditions at follow-up in participants without neurodegenerative and psychiatric diseases (n = 11,504). c, Associations of brain and peripheral organ aging with risk of incident psychiatric diseases and all-cause mortality in participants with psychological distress (symptoms of depression and anxiety) at baseline over 13 years follow-up (n = 3,958). d, Associations of brain and peripheral organ aging with incident NDs and all-cause mortality in healthy participants over 13 years follow-up (n = 43,616). e, Association between multiple markers (brain age gap, PRS for depression, and age) and risk of incident depression over 13 years follow-up (n = 43,616). Squares represent effect sizes (beta coefficients, ORs, or HRs) and error bars the corresponding 95% CIs in a-e. f, Cumulative incidence curves of depression across combined levels of brain age gap and PRS for depression. Participants were grouped into five bins based on the combined standardized scores: bin -2 (< -1.5 SD), bin -1 (-1.5 to -0.5 SD), bin 0 (-0.5 to +0.5 SD), bin +1 ( + 0.5 to +1.5 SD), and bin +2 (> +1.5 SD). Displayed HR reflects the depression risk per 1 SD increase in the combined scores. g, Change of top proteins in organ-specific (brain, kidney, intestine, and pancreas) aging clock that were also related to depression/anxiety with chronological age. Trajectories with age were fitted by Loess regression. Proteins in organismal model are preferentially colored as organ-specific if they are also included in organ-specific aging clocks. h, Effect of age on proteins in g. i, Protein-protein interaction network identified through STRING analysis. Displayed are interactions of the featured proteins from g and h, and their interacting proteins with a confidence score ≥ 0.4. j, Enriched biological pathways for featured proteins involved in aging and depression/anxiety. All relevant models were adjusted for age, sex, ethnicity, Townsend deprivation index, smoking, physical activity level, and recruitment center. Error bars indicate 95% CIs.