Plasma metabolites of a healthy lifestyle in relation to mortality and longevity: Four prospective US cohort studies
Journal article, 2024
Background: A healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity. Methods: In four large cohorts with 13,056 individuals and 28-year follow-up, we assessed five healthy lifestyle factors, used liquid chromatography mass spectrometry to profile plasma metabolites, and ascertained deaths with death certificates. The unique healthy lifestyle metabolomic signature was identified using an elastic regression. Multivariable Cox regressions were used to assess associations of the signature with mortality and longevity. Findings: The identified healthy lifestyle metabolomic signature was reflective of lipid metabolism pathways. Shorter and more saturated triacylglycerol and diacylglycerol metabolite sets were inversely associated with the healthy lifestyle score, whereas cholesteryl ester and phosphatidylcholine plasmalogen sets were positively associated. Participants with a higher healthy lifestyle metabolomic signature had a 17% lower risk of all-cause mortality, 19% for cardiovascular disease mortality, and 17% for cancer mortality and were 25% more likely to reach longevity. The healthy lifestyle metabolomic signature explained 38% of the association between the self-reported healthy lifestyle score and total mortality risk and 49% of the association with longevity. Conclusions: This study identifies a metabolomic signature that measures adherence to a healthy lifestyle and shows prediction of total and cause-specific mortality and longevity. Funding: This work was funded by the NIH, CIHR, AHA, Novo Nordisk Foundation, and SciLifeLab.
smoking
diet
physical activity
Translation to population health
metabolome
mortality
metabolomics
longevity
alcohol
lifestyle
BMI
Author
Anne Julie Tessier
Harvard School of Public Health
Fenglei Wang
Harvard School of Public Health
Liming Liang
Harvard School of Public Health
Clemens Wittenbecher
Chalmers, Life Sciences, Food and Nutrition Science
Danielle E. Haslam
Harvard School of Public Health
Brigham and Women's Hospital
A. Heather Eliassen
Harvard School of Public Health
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
Alberto Ascherio
Brigham and Women's Hospital
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
Francine Grodstein
Rush University Medical Center
Harvard School of Public Health
Kathryn Rexrode
Brigham and Women's Hospital
Jo Ann E. Manson
Brigham and Women's Hospital
Harvard School of Public Health
Raji Balasubramanian
University of Massachusetts
Clary B. Clish
Broad Institute
Miguel A. Martínez-González
University of Navarra
Harvard School of Public Health
Jorge E. Chavarro
Harvard School of Public Health
Brigham and Women's Hospital
Frank B. Hu
Harvard School of Public Health
Brigham and Women's Hospital
Marta Guasch-Ferré
Harvard School of Public Health
Novo Nordisk Foundation
Med
26666359 (ISSN) 26666340 (eISSN)
Vol. 5 3 224-238.e5Subject Categories
Cardiac and Cardiovascular Systems
Public Health, Global Health, Social Medicine and Epidemiology
Nutrition and Dietetics
DOI
10.1016/j.medj.2024.01.010
PubMed
38366602