Plasma metabolomic profiles associated with mortality and longevity in a prospective analysis of 13,512 individuals
Journal article, 2023
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.
Author
Fenglei Wang
Harvard School of Public Health
Anne Julie Tessier
Harvard School of Public Health
Liming Liang
Harvard School of Public Health
Clemens Wittenbecher
Harvard School of Public Health
Chalmers, Life Sciences, Food and Nutrition Science
Danielle E. Haslam
Harvard School of Public Health
Brigham and Women's Hospital
Gonzalo Fernández-Duval
University of Navarra
A. Heather Eliassen
Brigham and Women's Hospital
Harvard School of Public Health
Kathryn Rexrode
Harvard Medical School
Brigham and Women's Hospital
Deirdre K. Tobias
Harvard School of Public Health
Brigham and Women's Hospital
Jun Li
Brigham and Women's Hospital
Harvard School of Public Health
Oana Zeleznik
Brigham and Women's Hospital
Francine Grodstein
Rush University Medical Center
Miguel A. Martínez-González
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
University of Navarra
Harvard School of Public Health
Jordi Salas-Salvadó
Rovira i Virgili University
Institut d'Investigació Sanitària Pere Virgili (IISPV)
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Clary B. Clish
Broad Institute
Kyu Ha Lee
Harvard School of Public Health
Qi Sun
Harvard School of Public Health
Brigham and Women's Hospital
Meir J. Stampfer
Brigham and Women's Hospital
Harvard School of Public Health
Frank B. Hu
Harvard School of Public Health
Brigham and Women's Hospital
Marta Guasch-Ferré
Harvard School of Public Health
Novo Nordisk Foundation
University of Copenhagen
Nature Communications
2041-1723 (ISSN) 20411723 (eISSN)
Vol. 14 1 5744Subject Categories (SSIF 2011)
Public Health, Global Health, Social Medicine and Epidemiology
DOI
10.1038/s41467-023-41515-z
PubMed
37717037