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Examining the link between metabolism, mortality, and longevity

Staff Writer

October 20, 2023

October 20, 2023—A new study led by researchers at Harvard T.H. Chan School of Public Health has identified a group of metabolites—molecules resulting from bodily chemical processes such as digestion—associated with risk of mortality (early death), and another group linked with longevity.

The study was published on September 16 in Nature Communications.

While some research has examined the relationship between metabolism, mortality, and longevity in humans, findings have been limited because of small sample sizes, short study durations, and a low number of metabolites profiled. To learn more, the researchers developed a scoring system to track levels of metabolites in the blood of 11,634 American adults enrolled in the Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-up Study. They then looked at participants’ health outcomes, including longevity (defined as living to age 85 or older) and all-cause and specific-cause mortality. As a last step, the researchers replicated the analysis using health data from 1,878 Spanish adults enrolled in the PREvención con DIeta MEDiterránea (PREDIMED) study.

The researchers looked at various types of metabolites, including nucleosides (a metabolite found in DNA), amino acids (the metabolite that forms proteins), and lipids (the metabolite that forms fats). They found 72 metabolites that were positively associated with mortality and 32 that were inversely associated.

“Our findings suggest that differences in levels of nucleosides, amino acids, and several lipid subclasses can predict mortality,” the researchers wrote. The results also “highlight some potentially important metabolites and biological pathways in aging and diseases that may open up new avenues to incorporate these metabolomic markers in clinical and research settings.”

Co-authors of the study included Liming Liang, professor of statistical genetics in the Department of Epidemiology, and members of the Department of Nutrition: Fenglei Wang, doctoral student; Anne-Julie Tessier, research fellow; Danielle Haslam, research associate; A. Heather Eliassen, professor of nutrition and epidemiology; Deirdre Tobias, assistant professor; Jun Li, assistant professor; Miguel Martínez-González, adjunct professor; Kyu Ha Lee, assistant professor of integrative genomic epidemiology; Qi Sun, associate professor; Meir Stampfer, research professor; Marta Guasch-Ferre, adjunct associate professor; and Frank Hu, professor of nutrition and epidemiology and department chair.