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The cellular mechanisms by which noncaloric bioactives promote healthspan are not well understood, limiting their use in disease prevention. Here, we deploy a whole-organism, high-content screen in zebrafish to profile food-derived compounds for activation of autophagy, a cellular quality control mechanism that promotes healthy aging. We identify thymol and carvacrol as activators of autophagy and mitophagy through a transient dampening of the mitochondrial membrane potential. Chemical stabilization of thymol-induced mitochondrial depolarization blocks mitophagy activation, suggesting a mechanism originating from the mitochondrial membrane. Supplementation with thymol prevents excess liver fat accumulation in a mouse model of diet-induced obesity, improves\n                    <jats:italic>pink-1<\/jats:italic>\n                    -dependent heat stress resilience in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , and slows the decline of skeletal muscle performance while delaying epigenetic aging in SAMP8 mice. Thus, terpenoids from common herbs promote autophagy during aging and metabolic overload, making them attractive molecules for nutrition-based healthspan promotion.\n                  <\/jats:p>","DOI":"10.1038\/s43587-025-00957-4","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T09:15:11Z","timestamp":1758705311000},"page":"2003-2021","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Herbal terpenoids activate autophagy and mitophagy through modulation of bioenergetics and protect from metabolic stress, sarcopenia and epigenetic 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G.L., K.M., G.E.J., F.S., M.H., J.L.S.-G., B.J.B., P.L., B.B., A.-L.E., A.Z., J.R., A.H., L.T., S.M., M.C., J.N.F. and P.G. are employees of Nestl\u00e9 Research, part of Soci\u00e9t\u00e9 des Produits Nestl\u00e9 SA. Patents owned by Soci\u00e9t\u00e9 des Produits Nestl\u00e9 SA have been filed related to this work, and the list of inventors includes authors of this article. Patent application publications can be found using the following identifiers:\n                      \n                      ,\n                      \n                      and\n                      \n                      . M.A.Q., D.S.P. and S.A.V. are employees of NemaLife Inc., which has received fees from Nestl\u00e9 Research for preclinical services. The Regents of the University of California are the sole owners of patents and patent applications directed at epigenetic biomarkers and the mammalian array for which S.H. is a named inventor. S.H. is a founder and paid consultant of the nonprofit Epigenetic Clock Development Foundation, which licenses these patents. No new patents were filed for epigenetic age analysis as part of this study. S.H. is a principal investigator at Altos Labs. R.T.B. is a cofounder and employee of the nonprofit Epigenetic Clock Development Foundation. J.A. is a consultant and\/or scientific advisory board member of MitoBridge\/Astellas, MetroBiotech, Amazentis, Vandria, OrsoBio and NovMetapharma. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}