Inflammation, Metabolic Status and Mental Health as Potential Mediators of the Association Between Socioeconomic Deprivation and Frailty.

Frailty, a state of heightened vulnerability to stressors, is prevalent in older adults and imposes substantial health and economic burdens. While socioeconomic deprivation (measured by the Townsend Deprivation Index, TDI) is linked to adverse health outcomes, its specific associative relationship with frailty and the putative mediating roles of chronic inflammation, metabolic dysregulation, and mental health remain unclear. In this cross-sectional study of 264,475 middle-aged and older UK Biobank participants, frailty was assessed using the Fried phenotype criteria. Multinomial logistic regression examined TDI-frailty associations, and multiple mediation analyses (pathways: deprivation → mediators → frailty) evaluated effects of inflammatory (CRP), metabolic (vitamin D), and mental health markers, adjusted for sociodemographic, behavioral, and health-related covariates. Higher TDI scores were significantly associated with increased odds of pre-frail (OR = 1.060, P < 0.001) and frail (OR = 1.182, P < 0.001) status, with a stronger male association (OR = 4.680, P < 0.001) and dose-dependent gradient across quartiles. Collectively, mediators explained ~ 10% of the association, with depression (6.72%) and vitamin D (4.59%) being the strongest contributors. These findings highlight deprivation as a robust associative frailty predictor, particularly in males, and suggest targeted interventions may reduce risk in deprived populations.