Civiletto Gabriele, Brunetti Dario, Lizzo Giulia, Muller Kamila, Jacot Guillaume E, Daskalaki Ioanna, Sizzano Federico, Huh Minji, Di Meo Ivano, Colombo Maria Nicol, Sanchez-Garcia José L, Bétrisey Bertrand J, Zollinger Alix, Lino Patricia, Neal Christopher, Egesipe Anne-Laure, Richard Joy, Chimen Myriam, Hermant Aurélie, Brinon Benjamin, Texari Lorane, Metairon Sylviane, Qureshi Mohammed Adnan, Patel Dhaval S, Vanapalli Siva A, Malavolta Marco, Gao Arwen W, Lalou Amelia, Provinciali Mauro, Orlando Fiorenza, Tiranti Valeria, Brooke Robert T, Horvath Steve, Auwerx Johan, Feige Jerome N, Gut Philipp
Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland.
Health, Nutrition and Care, DSM-Firmenich, Kaiseraugst, Switzerland.
Nat Aging. 2025 Sep 24. doi: 10.1038/s43587-025-00957-4.
Small molecular food components contribute to the health benefits of diets rich in fruits, vegetables, herbs and spices. 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 pink-1-dependent heat stress resilience in Caenorhabditis elegans, 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.
