Intrinsic capacity–frailty phenotypes and subclinical inflammation in community-dwelling octogenarians: A cross-sectional analysis from the ilSIRENTE study

Chronic low-grade inflammation contributes to frailty and functional decline in aging. Intrinsic capacity (IC), defined as the composite of physical and mental reserves, complements frailty assessment by reflecting functional resilience. This cross-sectional analysis used baseline data from the ilSIRENTE cohort to examine the relationship between IC–frailty phenotypes and systemic inflammation in community-dwelling octogenarians and identify IC domains most closely related to inflammatory burden. IC was assessed across five domains (locomotion, cognition, vitality, psychological well-being, and sensory function), rescaled to a 0–100 range, and combined with frailty status to define four IC–frailty phenotypes (concordant frail, discordant low IC, discordant high IC, concordant robust). Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured, and a composite inflammatory burden score (0–3) was derived. The analysis included 311 participants (mean age 85.4 ± 4.7 years, 66.6 % women). Median CRP, IL-6, and TNF-α levels increased progressively from concordant robust to concordant frail groups ( p < 0.01). In the fully adjusted model, concordant frail participants had higher inflammation compared with concordant robust (β = 0.71; 95 % CI 0.04–1.37; p = 0.03), while discordant high IC and discordant low IC showed intermediate values without statistical significance. A significant linear trend was observed across ordered phenotypes (β per category increment = 0.21, 95 % CI 0.06 to 0.37). Locomotion and vitality emerged as the domains most strongly linked to inflammation. IC–frailty phenotypes show a biological gradient of subclinical inflammation, with higher IC having lower inflammation levels. Preserved locomotion reflects key functional correlates of resilience and vitality in advanced age. • Intrinsic capacity–frailty phenotypes display a biological inflammation gradient. • Reduced intrinsic capacity is associated with elevated CRP, IL-6, and TNF-α levels. • Locomotion and vitality drive the link between functional decline and inflammation. • Results suggest impaired resilience as a pathway of inflammaging in late life. • Integrating intrinsic capacity with biomarkers refines geroscience models of aging.