Cheng S, Larson MG, McCabe EL, Murabito JM, Rhee EP, Ho JE, Jacques PF, Ghorbani A, Magnusson M, Souza AL, Deik AA, Pierce KA, Bullock K, O'Donnell CJ, Melander O, Clish CB, Vasan RS, Gerszten RE, Wang TJ. Distinct metabolomic signatures are associated with longevity in humans. Nature communications. 6(6). 6791 p. PMID: 25864806 [PubMed] PMCID: PMC4396657 NIHMSID: NIHMS668518.
Alterations in metabolism influence lifespan in experimental models, but data in humans are lacking. Here we use liquid chromatography/mass spectrometry to quantify 217 plasma metabolites and examine their relation to longevity in a large cohort of men and women followed for up to 20 years. We find that, higher concentrations of the citric acid cycle intermediate, isocitrate, and the bile acid, taurocholate, are associated with lower odds of longevity, defined as attaining 80 years of age. Higher concentrations of isocitrate, but not taurocholate, are also associated with worse cardiovascular health at baseline, as well as risk of future cardiovascular disease and death. None of the metabolites identified are associated with cancer risk. Our findings suggest that some, but not all, metabolic pathways related to human longevity are linked to the risk of common causes of death.