Distinct metabolomic signatures are associated with longevity in humans.

Susan Cheng, Martin G Larson, Elizabeth L McCabe, Joanne M Murabito, Eugene P Rhee, Jennifer E Ho, Paul F Jacques, Anahita Ghorbani, Martin Magnusson, Amanda L Souza, Amy A Deik, Kerry A Pierce, Kevin Bullock, Christopher J O'Donnell, Olle Melander, Clary B Clish, Ramachandran S Vasan, Robert E Gerszten, Thomas J Wang

Journal: Nature communications 2016;6():6791

PMID: 25864806

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Abstract

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.

Address: Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (SC, MGL, JMM, JEH, CJO, RSV, TJW); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (SC); Department of Mathematics and Statistics, Boston University, Boston, MA (MGL); Department of Biostatistics, Boston University School of Public Health, Boston, MA (ELM); Cardiology Division (JEH, AG, CJO, REG), Cardiovascular Research Center (REG), and Renal Division (EPR), Massachusetts General Hospital, Harvard Medical School, Boston, MA; General Internal Medicine (JMM), Cardiology (JEH, RSV), and Preventive Medicine (RSV), Department of Medicine, Boston University School of Medicine, Boston, MA; Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA (PFJ); Department of Clinical Sciences, Lund University, Malmö (MM, OM); Broad Institute of MIT and Harvard, Cambridge, MA (ALS, AAD, KAP, KB, CBC, REG); National Heart, Lung & Blood Institute Division of Intramural Research, Bethesda, MD (CJO); and, Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (TJW).

DOI: 10.1038/ncomms7791

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MeSH Terms: Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Chromatography, Liquid, Female, Humans, Isocitrates, Longevity, Longitudinal Studies, Male, Mass Spectrometry, Metabolome, Middle Aged, Neoplasms, Odds Ratio, Prognosis, Survival Analysis, Taurocholic Acid