Abstract
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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 5744 |
| Tidsskrift | Nature Communications |
| Vol/bind | 14 |
| Udgave nummer | 1 |
| Antal sider | 11 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:The authors thank the participants and staff of the NHS, NHSII, HPFS, and PREDIMED for their valuable contributions. The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) and/or the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia, Wyoming. This study is supported by the National Institutes of Health’s grant 1R21AG070375 to M.G.-F. The NHS, NHSII, HPFS, and PREDIMED are supported by grants from the National Institutes of Health (UM1 CA186107, U01 CA176726, U01 CA167552, U01 HL145386, R01 CA49449, R01 HL034594, R01 HL088521, R01 CA67262, R01 HL35464, R01 HL60712, R01 CA50385, P01 CA87969, R01 AR049880, R01 DK112940, R01 DK119268, R01 DK120870, P30 DK046200, R01 HL118264, and R01 DK127601). F.W. is supported by the American Heart Association Postdoctoral Fellowship (Grant number: 897161). A.-J.T. is supported by the Canadian Institutes of Health Research Postdoctoral Fellowship Award (Grant number: 181882). M.G.-F. is supported by Novo Nordisk Foundation grant NNF18CC0034900. The funders had no role in the design, conduct, analysis, or reporting of this study. The funding sources did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Funding Information:
The authors thank the participants and staff of the NHS, NHSII, HPFS, and PREDIMED for their valuable contributions. The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) and/or the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia, Wyoming. This study is supported by the National Institutes of Health’s grant 1R21AG070375 to M.G.-F. The NHS, NHSII, HPFS, and PREDIMED are supported by grants from the National Institutes of Health (UM1 CA186107, U01 CA176726, U01 CA167552, U01 HL145386, R01 CA49449, R01 HL034594, R01 HL088521, R01 CA67262, R01 HL35464, R01 HL60712, R01 CA50385, P01 CA87969, R01 AR049880, R01 DK112940, R01 DK119268, R01 DK120870, P30 DK046200, R01 HL118264, and R01 DK127601). F.W. is supported by the American Heart Association Postdoctoral Fellowship (Grant number: 897161). A.-J.T. is supported by the Canadian Institutes of Health Research Postdoctoral Fellowship Award (Grant number: 181882). M.G.-F. is supported by Novo Nordisk Foundation grant NNF18CC0034900. The funders had no role in the design, conduct, analysis, or reporting of this study. The funding sources did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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