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Plasma metabolomic profiles associated with mortality and longevity in a prospective analysis of 13,512 individuals

Author

Listed:
  • Fenglei Wang

    (Harvard T.H. Chan School of Public Health)

  • Anne-Julie Tessier

    (Harvard T.H. Chan School of Public Health)

  • Liming Liang

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health)

  • Clemens Wittenbecher

    (Harvard T.H. Chan School of Public Health
    Chalmers University of Technology)

  • Danielle E. Haslam

    (Harvard T.H. Chan School of Public Health
    Brigham and Women’s Hospital and Harvard Medical School)

  • Gonzalo Fernández-Duval

    (University of Navarra)

  • A. Heather Eliassen

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health
    Brigham and Women’s Hospital and Harvard Medical School)

  • Kathryn M. Rexrode

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital, and Harvard Medical School)

  • Deirdre K. Tobias

    (Harvard T.H. Chan School of Public Health
    Brigham and Women’s Hospital and Harvard Medical School)

  • Jun Li

    (Harvard T.H. Chan School of Public Health
    Brigham and Women’s Hospital and Harvard Medical School)

  • Oana Zeleznik

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Francine Grodstein

    (Rush University Medical Center)

  • Miguel A. Martínez-González

    (Harvard T.H. Chan School of Public Health
    University of Navarra
    Instituto de Salud Carlos III (ISCIII))

  • Jordi Salas-Salvadó

    (Instituto de Salud Carlos III (ISCIII)
    Unitat de Nutrició Humana
    Institut d’Investigació Sanitària Pere Virgili (IISPV))

  • Clary Clish

    (Broad Institute of MIT and Harvard)

  • Kyu Ha Lee

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health)

  • Qi Sun

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health
    Brigham and Women’s Hospital and Harvard Medical School)

  • Meir J. Stampfer

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health
    Brigham and Women’s Hospital and Harvard Medical School)

  • Frank B. Hu

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health
    Brigham and Women’s Hospital and Harvard Medical School)

  • Marta Guasch-Ferré

    (Harvard T.H. Chan School of Public Health
    University of Copenhagen
    University of Copenhagen)

Abstract

Experimental studies reported biochemical actions underpinning aging processes and mortality, but the relevant metabolic alterations in humans are not well understood. Here we examine the associations of 243 plasma metabolites with mortality and longevity (attaining age 85 years) in 11,634 US (median follow-up of 22.6 years, with 4288 deaths) and 1878 Spanish participants (median follow-up of 14.5 years, with 525 deaths). We find that, higher levels of N2,N2-dimethylguanosine, pseudouridine, N4-acetylcytidine, 4-acetamidobutanoic acid, N1-acetylspermidine, and lipids with fewer double bonds are associated with increased risk of all-cause mortality and reduced odds of longevity; whereas L-serine and lipids with more double bonds are associated with lower mortality risk and a higher likelihood of longevity. We further develop a multi-metabolite profile score that is associated with higher mortality risk. Our findings suggest that differences in levels of nucleosides, amino acids, and several lipid subclasses can predict mortality. The underlying mechanisms remain to be determined.

Suggested Citation

  • Fenglei Wang & Anne-Julie Tessier & Liming Liang & Clemens Wittenbecher & Danielle E. Haslam & Gonzalo Fernández-Duval & A. Heather Eliassen & Kathryn M. Rexrode & Deirdre K. Tobias & Jun Li & Oana Ze, 2023. "Plasma metabolomic profiles associated with mortality and longevity in a prospective analysis of 13,512 individuals," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41515-z
    DOI: 10.1038/s41467-023-41515-z
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    References listed on IDEAS

    as
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    2. Rosen, Allison B. & Stewart, Susan T. & Cutler, David M., 2009. "Forecasting the Effects of Obesity and Smoking on U.S. Life Expectancy," Scholarly Articles 5344184, Harvard University Department of Economics.
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