PUBLICATION
Herbal terpenoids activate autophagy and mitophagy through modulation of bioenergetics and protect from metabolic stress, sarcopenia and epigenetic aging
- Authors
- Civiletto, G., Brunetti, D., Lizzo, G., Muller, K., Jacot, G.E., Daskalaki, I., Sizzano, F., Huh, M., Di Meo, I., Colombo, M.N., Sanchez-Garcia, J.L., Bétrisey, B.J., Zollinger, A., Lino, P., Neal, C., Egesipe, A.L., Richard, J., Chimen, M., Hermant, A., Brinon, B., Texari, L., Metairon, S., Qureshi, M.A., Patel, D.S., Vanapalli, S.A., Malavolta, M., Gao, A.W., Lalou, A., Provinciali, M., Orlando, F., Tiranti, V., Brooke, R.T., Horvath, S., Auwerx, J., Feige, J.N., Gut, P.
- ID
- ZDB-PUB-250925-9
- Date
- 2025
- Source
- Nature aging : (Journal)
- Registered Authors
- Civiletto, Gabriele, Gut, Philipp, Richard, Joy
- Keywords
- none
- MeSH Terms
-
- Aging*/drug effects
- Aging*/genetics
- Animals
- Autophagy*/drug effects
- Caenorhabditis elegans/drug effects
- Cymenes/pharmacology
- Energy Metabolism*/drug effects
- Epigenesis, Genetic*/drug effects
- Male
- Membrane Potential, Mitochondrial/drug effects
- Mice
- Mitophagy*/drug effects
- Muscle, Skeletal/drug effects
- Sarcopenia*/prevention & control
- Stress, Physiological*/drug effects
- Terpenes*/pharmacology
- Zebrafish
- PubMed
- 40993327 Full text @ Nat Aging
Citation
Civiletto, G., Brunetti, D., Lizzo, G., Muller, K., Jacot, G.E., Daskalaki, I., Sizzano, F., Huh, M., Di Meo, I., Colombo, M.N., Sanchez-Garcia, J.L., Bétrisey, B.J., Zollinger, A., Lino, P., Neal, C., Egesipe, A.L., Richard, J., Chimen, M., Hermant, A., Brinon, B., Texari, L., Metairon, S., Qureshi, M.A., Patel, D.S., Vanapalli, S.A., Malavolta, M., Gao, A.W., Lalou, A., Provinciali, M., Orlando, F., Tiranti, V., Brooke, R.T., Horvath, S., Auwerx, J., Feige, J.N., Gut, P. (2025) Herbal terpenoids activate autophagy and mitophagy through modulation of bioenergetics and protect from metabolic stress, sarcopenia and epigenetic aging. Nature aging. :.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping