The multi-institutional effort found that the herbal terpenoids could also promote mitophagy during aging across multiple species, including zebrafish, C. elegans (nematodes) and mice. Mitophagy is a process in which damaged mitochondria are recycled to permit a renewal with healthy mitochondria.
“This study broadens the mechanistic understanding of the health benefits mediated by oregano and thyme terpenoids and shows a potential link between their functions as secondary metabolites in plants to effects on mitochondrial bioenergetics, autophagy and mitophagy in eukaryotic cells,” wrote the researchers in Nature Aging.
“Thymol reaches high amounts in common oregano and thyme species and can be enriched in essential oregano oils making it a relatively simple to source and a cost-efficient ingredient for nutrition-based prevention, including as enhancers of autophagy-mediated benefits of CR [calorie restriction] and IF [intermittent fasting] regimens.”
Aging
There are 12 hallmarks of aging, outlined in a 2023 review by Professor Carlos López-Otín and co-workers, and dietary ingredients can potentially act on one or more of these processes. Two of these hallmarks are disabled macroautophagy and mitochondrial dysfunction.
Autophagy is thought to be activated during caloric restriction and intermittent fasting, but this can require an extended period of low-calorie intake. There are also reports of large variability in the efficacy of fasting regimes from one person to the next.
One approach to get around these challenges is to explore the potential of small molecules, preferably food-grade ingredients, to activate autophagy and mimic the benefits of caloric restriction and fasting, explained the research team, which included scientists from Nestlé Research, the University of Milan, the École Polytechnique Fédérale de Lausanne, Fondazione IRCCS Istituto Neurologico Carlo Besta (Milan), NemaLife, IRCCS INRCA (Ancona, Italy), Epigenetic Clock Development Foundation (Los Angeles), and the University of California, Los Angeles.
Study details
For the new study, the researchers used zebrafish to screen a range of natural compounds found in food and identified thymol and carvacrol as having potential to activate autophagy.
When tested in other animal models, the compounds were found to make the nematode C. elegans more resistant to heat stress, while the compounds also slowed muscle decline and epigenetic aging in older mice.
Thymol supplementation was found to prevent fatty liver in obese mice eating a high-fat diet.
“Rapid absorption in the duodenum further suggests that oral intake leads to transient peaks in thymol and its conjugates, reaching levels sufficient to activate autophagy in tissues before they are cleared,” the researchers added.
“Thus, terpenoids from common herbs promote autophagy during aging and metabolic overload, making them attractive for nutrition-based healthspan promotion.”
Translational science
“This study exemplifies how translational science can bridge natural bioactives with cellular mechanisms of aging,” said Dr. Siva Vanapalli, CEO of NemaLife and co-author on the paper. “We are honored to support this pioneering work with our AI-powered high-throughput C. elegans platform, accelerating discovery of dietary ingredients that hold real potential to improve healthspan.”
Dr. Vanapalli told NutraIngredients that the study was not designed to benchmark thymol and carvacrol against other healthy-aging bioactives.
“That said, they sit on the same autophagy map as urolithin A, spermidine, sulforaphane and quercetin, each with published, autophagy-linked healthspan benefits in the C. elegans model," he said. “Comparative profiling and smart design of combinations to unlock synergy would be a compelling next step.” Clinical studies will be required to translate the findings on thymol and carvacrol into preventive nutrition approaches leveraging its autophagy-inducing mechanisms.
Nestlé’s premium position in healthspan research
Advancements in healthspan, longevity and cellular aging are accelerating, and one company positioning itself strategically within this growing area is Nestlé, which continues to invest in promising ingredients and scientific substantiation to target the hallmarks of aging.
The company has previously published research on the benefits of a range of bioactives, including nicotinamide, pyridoxine, oleuropein and trigonelline, for cellular aging.
Source: Nature Aging. 2025. doi: 10.1038/s43587-025-00957-4. “Herbal terpenoids activate autophagy and mitophagy through modulation of bioenergetics and protect from metabolic stress, sarcopenia and epigenetic aging”. Authors: G. Civiletto, et al.
