Bio-Psycho-Social Frailty and Mortality Risk in the GreatAge: The Salus in Apulia Study

This study explores the complex interplay between physical frailty and late-life depression (LLD) in predicting mortality among older adults. Drawing from the GreatAge / Salus in Apulia Study, a longitudinal cohort of individuals aged 65 years and older, the research examines how frailty and depression independently and synergistically impact survival outcomes. Participants were stratified into four phenotypic groups: healthy controls, only frail, only depressed, and frail depression, with survival differences analyzed using Kaplan- Meier curves and Cox proportional hazard models. The results demonstrate that frailty and depression significantly increase mortality risk, with the frail depression phenotype showing the highest hazard ratios. Elevated levels of inflammatory markers (e.g., IL-6, CRP) and multimorbidity scores were observed in individuals with combined frailty and depression, indicating a compounded biological and clinical burden. These findings emphasize the need for integrated, multidimensional interventions targeting both physical and psychological vulnerabilities to improve health outcomes and longevity in aging populations. This study contributes to a growing body of evidence advocating for a biopsychosocial framework in geriatric care, aligning with global public health strategies to promote healthy aging.