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Host and microbiota metabolic signals in aging and longevity

Abstract

Aging is an inevitable biochemical process that adversely affects personal health and poses ever-increasing challenges to society. Recent research has revealed the crucial role of metabolism in regulating aging and longevity. During diverse metabolic processes, the host organism and their symbiotic partners—the microbiota—produce thousands of chemical products (metabolites). Emerging studies have uncovered specific metabolites that act as signaling molecules to actively regulate longevity. Here we review the latest progress in understanding the molecular mechanisms by which metabolites from the host and/or microbiota promote longevity. We also highlight state-of-the-art technologies for discovering, profiling and imaging aging- and longevity-regulating metabolites and for deciphering the molecular basis of their actions. The broad application of these technologies in aging research, together with future advances, will foster the systematic discovery of aging- and longevity-regulating metabolites and their signaling pathways. These metabolite signals should provide promising targets for developing new interventions to promote longevity and healthy aging.

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Fig. 1: Chemical structures and mechanisms of aging-regulating host metabolites.
Fig. 2: Microbial metabolites in aging regulation.
Fig. 3: Mechanisms by which microbial metabolites regulate host longevity.
Fig. 4: Comparative metabolomics in aging research.
Fig. 5: Chemical proteomics for identifying metabolite-binding targets.
Fig. 6: Chemical imaging methods for aging-regulating metabolites.

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Acknowledgements

This work was supported by NIH grants R01AG045183 (M.C.W.), R01AT009050 (M.C.W.), R01AG062257 (M.C.W.), P01AG066606 (M.C.W.) and DP1DK113644 (M.C.W.) and by the Welch Foundation (M.C.W.). M.C.W. is a Howard Hughes Medical Institute Investigator. We apologize to colleagues whose work was not cited owing to space limitations.

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Zhou, Y., Hu, G. & Wang, M.C. Host and microbiota metabolic signals in aging and longevity. Nat Chem Biol 17, 1027–1036 (2021). https://doi.org/10.1038/s41589-021-00837-z

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