Metabolite signatures of chronological age, aging, survival, and longevity

Authors: SEBASTIANI, PAOLA - Tufts Medical Center; MONTI, STEFANO - Boston University; LUSTGARTEN, MICHAEL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SONG, ZEYUAN - Boston University; ELLIS, DYLAN - Institute For Systems Biology; TIAN, QU - National Institute On Aging (NIA, NIH); SCHWAIGER-HABER, MICHAELA - Washington University; STANCLIFF, ETHAN - Washington University; ARDISSON KORAT, ANDRES - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GURINOVICH, ANASTASIA - Tufts Medical Center; KARAGIANNIS, TANYA - Tufts Medical Center; LESCHYK, ANASTASIA - Boston University; LI, MENGZE - Boston University; LORDS, HANNAH - Boston University; SHORT, MEGHAN - Tufts Medical Center; XIANG, QINGYAN - Vanderbilt University Medical Center; MARRON, MEGHAN - University Of Pittsburgh; FEITOSA, MARY - Washington University; WOJCZYNSKI, MARY - Washington University; O'CONNELL, JEFF - University Of Maryland School Of Medicine; MONTASSER, MAY - University Of Maryland; SCHORK, NICHOLAS - Translational Genomics Research Institute; ARBEEV, KONSTANTIN - Duke University; YASHIN, ANATOLIY - Duke University; KRISTENSEN, KAARE - University Of Southern Denmark; ANDERSEN, STACY - Boston University; FERRUCCI, LUIGI - National Institute On Aging (NIA, NIH); RAPPAPORT, NOA - Buck Institute For Age Research; PATTI, GARY - Washington University; PERLS, THOMAS - Boston University

Submitted to: Cell Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/10/2024
Publication Date: 11/26/2024
Citation: Sebastiani, P., Monti, S., Lustgarten, M., Song, Z., Ellis, D., Tian, Q., Schwaiger-Haber, M., Stancliff, E., Ardisson Korat, A., Gurinovich, A., Karagiannis, T., Leschyk, A., Li, M., Lords, H., Short, M., Xiang, Q., Marron, M.M., Feitosa, M., Wojczynski, M., O'Connell, J., Montasser, M., Schork, N., Arbeev, K., Yashin, A., Kristensen, K., Andersen, S.L., Ferrucci, L., Rappaport, N., Patti, G., Perls, T.T. 2024. Metabolite signatures of chronological age, aging, survival, and longevity . Cell Reports. https://doi.org/10.1016/j.celrep.2024.114913.
DOI: https://doi.org/10.1016/j.celrep.2024.114913

Interpretive Summary: Aging impacts multiple physiological functions, which puts older individuals at a higher risk for disease and mortality. Identification of metabolites and their corresponding pathways that serve as biomarkers of aging, extreme human longevity and mortality is an ongoing process-in this manuscript, we identified significant associations for metabolites derived from tryptophan metabolism and mitochondrial function with aging, mortality risk, and/or extreme longevity. Furthermore, our findings suggest a role for diet quality on metabolite profiles that were associated with healthy aging.

Technical Abstract: Metabolites that mark aging are not fully known. We analyze 408 plasma metabolites in Long Life Family Study participants to characterize markers of age, aging, extreme longevity, and mortality. We identify 308 metabolites associated with age, 258 metabolites that change over time, 230 metabolites associated with extreme longevity, and 152 metabolites associated with mortality risk. We replicate many associations in independent studies. By summarizing the results into 19 signatures, we differentiate between metabolites that may mark aging-associated compensatory mechanisms from metabolites that mark cumulative damage of aging and from metabolites that characterize extreme longevity. We generate and validate a metabolomic clock that predicts biological age. Network analysis of the age-associated metabolites reveals a critical role of essential fatty acids to connect lipids with other metabolic processes. These results characterize many metabolites involved in aging and point to nutrition as a source of intervention for healthy aging therapeutics.