A multidimensional biomarker model of vitality and its associations with intrinsic capacity and frailty.

<h4>Background</h4>The World Health Organisation has identified intrinsic capacity (IC) as a key determinant of healthy ageing. Within the IC framework, vitality reflects physiological reserve arising from neuromuscular, metabolic and inflammatory/stress-response systems. However, this multidomain physiological construct has not been empirically validated, and vitality is often operationalised using nutritional assessments alone.<h4>Objectives</h4>We evaluated a biomarker-derived vitality construct and examined its associations with IC domains and frailty, compared to nutritional measures.<h4>Methods</h4>Cross-sectional analysis of 300 community-dwelling, functionally-independent older adults (mean (SD) age 67.4 (7.1) years; 69% female) was conducted using exploratory (EFA) and confirmatory factor analyses (CFA) to characterise the latent structure of biomarker-defined vitality. Factor scores were examined for associations with IC domains, composite IC and frailty using linear regression, compared with the Mini Nutritional Assessment-Short Form (MNA-SF).<h4>Results</h4>EFA supported a multidimensional structure with biomarkers clustering into neuromuscular, metabolic and inflammatory domains. CFA supported a correlated three-factor model for vitality; while a bifactor model showed superior global fit, general factor dominance was limited (ECV = 0.28; ωH = 0.26), with most variance at the domain level. Higher neuromuscular vitality was associated with greater composite IC (β = 1.39, 95% CI 0.25-2.54) and cognitive capacity (β = 1.74, 95% CI 0.52-2.95). A better metabolic vitality profile was associated with higher locomotor capacity (β = 1.74, 95% CI 0.58-2.91), while a more favourable inflammatory vitality profile was associated with higher locomotor capacity (β = 1.33, 95% CI 0.09-2.57) and reduced frailty (β = -0.11, 95% CI - 0.22 to -0.022). In contrast, MNA-SF scores were associated only with lower frailty (β = -0.09, 95% CI - 0.17 to -0.004), and not with IC.<h4>Conclusions</h4>Vitality is better represented as a multidimensional, physiological construct than by nutrition-based measures alone. Distinct biomarker-derived vitality domains were associated with IC and frailty, supporting its role in characterising physiological determinants of healthy ageing. Longitudinal research is required to establish its prognostic value.