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Background: Metabolic pathways that give rise to functional decline and mobility disability in older adults are incompletely understood.

Methods: To identify metabolic perturbations that may affect functional decline, nontargeted metabolomics was used to measure 350 metabolites in baseline plasma from 313 black men in the Health ABC Study (median age 74 years). Usual gait speed was measured over 20 m. Cross-sectional relationships between gait speed and metabolites were explored with partial correlations adjusted for age, study site, and smoking status. Risk of incident mobility disability (two consecutive reports of severe difficulty walking quarter mile or climb 10 stairs) over 13 years of follow-up was explored with Cox regression models among 307 men who were initially free of mobility disability. Significance was determined at p ≤ .01 and q (false discovery rate) ≤ 0.30.

Results: Two metabolites were correlated with gait speed: salicylurate (r = -.19) and 2-hydroxyglutarate (r = -.18). Metabolites of amino acids and amino acid degradation (indoxy sulfate; hazard ratio [HR] = 1.48, 95% confidence interval [CI] = 1.09-2.03, symmetric dimethylarginine; HR = 3.58, 95% CI = 1.57-8.15, N-carbamoyl beta-alanine; HR = 1.91, 95% CI = 1.16-3.14, quinolinate; HR = 2.56, 95% CI = 1.65-3.96) and metabolites related to kidney function (aforementioned symmetric dimethylarginine and indoxy sulfate as well as creatinine; HR = 5.91, 95% CI = 2.06-16.9, inositol; HR = 2.70, 95% CI = 1.47-4.97) were among the 23 metabolites associated with incident mobility disability.

Conclusions: This study highlights the potential role of amino acid derivatives and products and kidney function early in the development of mobility disability and suggests metabolic profiles could help identify individuals at risk of functional decline.