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 () and Thomas J. Wang ()
Additional contact information
Susan Cheng: Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine
Martin G. Larson: Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine
Elizabeth L. McCabe: Boston University School of Public Health
Joanne M. Murabito: Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine
Eugene P. Rhee: Massachusetts General Hospital, Harvard Medical School
Jennifer E. Ho: Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine
Paul F. Jacques: Tufts University
Anahita Ghorbani: Massachusetts General Hospital, Harvard Medical School
Martin Magnusson: Lund University
Amanda L. Souza: Broad Institute of MIT and Harvard
Amy A. Deik: Broad Institute of MIT and Harvard
Kerry A. Pierce: Broad Institute of MIT and Harvard
Kevin Bullock: Broad Institute of MIT and Harvard
Christopher J. O’Donnell: Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine
Olle Melander: Lund University
Clary B. Clish: Broad Institute of MIT and Harvard
Ramachandran S. Vasan: Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine
Robert E. Gerszten: Massachusetts General Hospital, Harvard Medical School
Thomas J. Wang: Vanderbilt University

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7791

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