Plasma metabolites of a healthy lifestyle in relation to mortality and longevity: Four prospective US cohort studies

Anne-Julie Tessier; Fenglei Wang; Liming Liang; Clemens Wittenbecher; Danielle E Haslam; A Heather Eliassen; Deirdre K Tobias; Jun Li; Oana A Zeleznik; Alberto Ascherio; Qi Sun; Meir J Stampfer; Francine Grodstein; Kathryn M Rexrode; JoAnn E Manson; Raji Balasubramanian; Clary B Clish; Miguel A Martínez-González; Jorge E Chavarro; Frank B Hu; Marta Guasch-Ferré

doi:10.1016/j.medj.2024.01.010

Plasma metabolites of a healthy lifestyle in relation to mortality and longevity: Four prospective US cohort studies

Med. 2024 Mar 8;5(3):224-238.e5. doi: 10.1016/j.medj.2024.01.010. Epub 2024 Feb 15.

Authors

Anne-Julie Tessier¹, Fenglei Wang², Liming Liang³, Clemens Wittenbecher⁴, Danielle E Haslam⁵, A Heather Eliassen⁶, Deirdre K Tobias⁷, Jun Li⁷, Oana A Zeleznik⁸, Alberto Ascherio⁵, Qi Sun⁵, Meir J Stampfer⁶, Francine Grodstein⁹, Kathryn M Rexrode¹⁰, JoAnn E Manson¹¹, Raji Balasubramanian¹², Clary B Clish¹³, Miguel A Martínez-González¹⁴, Jorge E Chavarro⁶, Frank B Hu⁶, Marta Guasch-Ferré¹⁵

Affiliations

¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: ajtessier@hsph.harvard.edu.
² Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴ Chalmers University of Technology, Gothenburg, Sweden.
⁵ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
¹⁰ Division of Women's Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹¹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹² Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA, USA.
¹³ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁴ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
¹⁵ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Public Health and Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: mguasch@hsph.harvard.edu.

PMID: 38366602
PMCID: PMC10940196 (available on 2025-03-08)
DOI: 10.1016/j.medj.2024.01.010

Abstract

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.

Keywords: BMI; Translation to population health; alcohol; diet; lifestyle; longevity; metabolome; metabolomics; mortality; physical activity; smoking.

MeSH terms

Cohort Studies
Healthy Lifestyle*
Humans
Longevity*
Prospective Studies
Risk Factors

Abstract

MeSH terms

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