Abstract
Functional decline is a common condition among older adults but mechanisms that give rise to functional decline and disability are incompletely understood. To identify metabolic perturbations that may impact functional decline, non-targeted metabolomics was used to measure 350 metabolites in baseline plasma from 313 black men in the Health, Aging and Body Composition Study (median age 74 years, median BMI 26.7). Usual gait speed was measured over 20 meters. Cross-sectional relationships between gait speed and metabolites were explored with Pearson partial correlations adjusted for age, study site and smoking status. Risk of incident mobility disability (2 consecutive reports of inability to walk ¼ mile or climb 10 stairs) over 13 years of follow-up was additionally explored with cox regression models among 307 men who were initially free of mobility disability. Significance was determined at p≤0.01 and q≤0.30. Ten metabolites were correlated with gait speed. The most strongly correlated were hydroxyglutarate (r=-0.18), gluconurate (r=-0.18), homogentisate (r=-0.16), salicylurate (r=-0.19), and tryptophan (r=0.15). Sixteen metabolites; all uniqe from gait speed-correlated metabolites, were associated with incident mobility disability. The top metabolites were creatine (HR 5.21, 95% CI 1.85–14.7); symmetric dimethylarginine, a biomarker of kidney function (HR=3.30, 95% CI=1.46–7.48); inositol (HR 2.73, 95% CI 1.48–5.02) and quinolate; a metabolite of tryptophan degradation (HR 2.54, 95% CI 1.64–3.93). This hypothesis generating study identified 26 involved in biological mechanisms including tryptophan metabolism, prospectively associated with functional decline in older men. The novel function-related metabolites identified here may help target future investigation of perturbed metabolic pathways.