Metabolites Associated with Vigor to Frailty Among Community-Dwelling Older Black Men

Black versus white older Americans are more likely to experience frailty, a condition associated with adverse health outcomes. To reduce racial disparities in health, a complete understanding of the pathophysiology of frailty is needed. Metabolomics may further our understanding by characterizing differences in the body during a vigorous versus frail state. We sought to identify metabolites and biological pathways associated with vigor to frailty among 287 black men ages 70-81 from the Health, Aging, and Body Composition study. Using liquid chromatography-mass spectrometry, 350 metabolites were measured in overnight-fasting plasma. The Scale of Aging Vigor in Epidemiology (SAVE) measured vigor to frailty based on weight change, strength, energy, gait speed, and physical activity. Thirty-seven metabolites correlated with SAVE scores (p < 0.05), while adjusting for age and site. Fourteen metabolites remained significant after multiple comparisons adjustment (false discovery rate < 0.30). Lower values of tryptophan, methionine, tyrosine, asparagine, C14:0 sphingomyelin, and 1-methylnicotinamide, and higher values of glucoronate, N-carbamoyl-beta-alanine, isocitrate, creatinine, C4-OH carnitine, cystathionine, hydroxyphenylacetate, and putrescine were associated with frailer SAVE scores. Pathway analyses identified nitrogen metabolism, aminoacyl-tRNA biosynthesis, and the citric acid cycle. Future studies need to confirm these SAVE-associated metabolites and pathways that may indicate novel mechanisms involved in the frailty syndrome.