Serum metabolites associate with physical performance among middle-aged adults: Evidence from the Bogalusa Heart Study

Age-related declines in physical performance predict cognitive impairment, disability, chronic disease exacerbation, and mortality. We conducted a metabolome-wide association study of physical performance among Bogalusa Heart Study participants. Bonferroni corrected multivariate-adjusted linear regression was employed to examine cross-sectional associations between single metabolites and baseline gait speed (N=1,227) and grip strength (N=1,164). In a sub-sample of participants with repeated assessments of gait speed (N=282) and grip strength (N=201), significant metabolites from the cross-sectional analyses were tested for association with change in physical performance over 2.9 years of follow-up. Thirty-five and seven metabolites associated with baseline gait speed and grip strength respectively, including six metabolites that associated with both phenotypes. Three metabolites associated with preservation or improvement in gait speed over follow-up, including: sphingomyelin (40:2) (P=2.6×10(-4)) and behenoyl sphingomyelin (d18:1/22:0) and ergothioneine (both P<0.05). Seven metabolites associated with declines in gait speed, including: 1-carboxyethylphenylalanine (P=8.8×10(-5)), and N-acetylaspartate, N-formylmethionine, S-adenosylhomocysteine, N-acetylneuraminate, N2,N2-dimethylguanosine, and gamma-glutamylphenylalanine (all P<0.05). Two metabolite modules reflecting sphingolipid and bile acid metabolism associated with physical performance (minimum P=7.6×10(-4)). These results add to the accumulating evidence suggesting an important role of the human metabolome in physical performance and specifically implicate lipid, nucleotide, and amino acid metabolism in early physical performance decline.