New study reveals potential for combating age-related diseases and improving mobility, endurance and cellular protection.
A new study published in Cell Metabolism has demonstrated that ergothioneine, a naturally occurring compound found in mushrooms and fermented foods, improves healthspan in aged animals by enhancing mobility, endurance and stress resistance while protecting against cellular damage [1]. The research, led by Leibniz Institute for Analytical Sciences (ISAS) and involving collaborations across several international institutions, sheds light on how ergothioneine impacts age-related biomarkers and provides insight into its therapeutic potential for conditions such as sarcopenia and other age-related diseases.
“Our analyses now finally provide clarity about the mechanism and also show that ergothioneine has promising therapeutic potential for the prevention of age-related diseases,” commented Dr Miloš Filipović, head of the ERC Sulfaging research group at ISAS [2].
Longevity.Technology: This study highlights the growing focus on healthspan rather than lifespan in aging research, reflecting the increasing priority placed on maintaining physical and cellular health as we age. With ergothioneine now shown to improve endurance and mitigate aging processes in animal models, it could represent an important step toward addressing the challenges of age-related diseases, such as Alzheimer’s and sarcopenia, and extending the years spent in good health – especially since the molecule is already widely available in supplement form.
The research team, which included scientists from the University of Belgrade, Heidelberg University and the University of Cambridge, investigated the effects of ergothioneine in multiple animal models, including everyone’s favorite nematode Caenorhabditis elegans as well as rats. In the nematodes, treatment with ergothioneine from early adulthood not only extended lifespan but also improved mobility and stress resistance while reducing biomarkers of aging [1].
“As the animals got older, the contrast with the control group became more significant. In addition, we did not observe any undesirable side effects – nor did other studies,” explained Dr Dunja Petrovic, whose doctoral work at ISAS was central to the publication [2].
Enhanced endurance and muscle health in mammals
The positive effects of ergothioneine were not limited to nematodes; researchers at the University of Belgrade observed significant improvements in endurance, muscle mass and vascularization in rats treated with the compound. Over a three-week period, nine-month-old rats received daily doses of 10 milligrams of ergothioneine – equivalent to the amount found in approximately 4.5 grams of dried oyster mushrooms.
In addition to improved endurance, the researchers reported an increase in muscle stem cells and the formation of new small blood vessels in muscle tissue, highlighting its potential role in preventing sarcopenia [1].
Molecular mechanism – boosting cellular defenses and NAD+ levels
Using mass spectrometry and cell culture analyses, the team uncovered the molecular mechanism behind these observations. Ergothioneine serves as an alternative substrate for the enzyme cystathionine-γ-lyase (CSE), a key player in the production of hydrogen sulfide (H₂S) – a signaling molecule that protects cells from oxidative stress via a process known as persulfidation. Reduced persulfidation has been associated with aging and diseases such as cardiovascular and neurodegenerative conditions.
The researchers found that ergothioneine increased persulfidation of a specific enzyme, glycerol-3-phosphate dehydrogenase (GPDH), which in turn elevated levels of NAD+, a coenzyme known for its role in promoting longevity and metabolic health [1].
“The human body is not able to produce ergothioneine itself. However, such a specific utilization mechanism suggests that it is very important for us,” noted Petrovic [2].
This mechanism builds on earlier work by the same research team, which demonstrated in 2019 that persulfidation decreases with age but can be positively influenced by dietary interventions [3]. By stimulating this critical cellular process, ergothioneine emerges as a potential tool for mitigating the effects of aging at the molecular level.
Human studies planned to explore performance-enhancing effects
To further explore its benefits, the researchers conducted a short-term study with younger rats, administering ergothioneine daily for five days. The results revealed a notable increase in endurance and elevated NAD+ levels in the blood serum, suggesting the compound’s potential for enhancing physical performance [1].
“This indicates that ergothioneine influences the metabolism in a similar way to performance-enhancing agents,” said Filipović [2].
Encouraged by these findings, Filipović and his team plan to extend their research to human trials to evaluate whether ergothioneine could offer similar benefits in terms of physical performance and resistance to age-related decline.
By providing clarity on ergothioneine’s molecular mechanism, this study will hopefully open the door to therapeutics that can slow or prevent age-related diseases and improve quality of life. With further research, the compound may hold promise for maintaining healthspan in humans, addressing challenges such as sarcopenia, cardiovascular decline and neurodegeneration.
[1] https://www.sciencedirect.com/science/article/pii/S155041312400490X
[2] https://www.isas.de/en/press/archive/prolonged-health-with-ergothioneine
[3] https://pubmed.ncbi.nlm.nih.gov/31735592/
