Supplementation with a high dose of the amino acid ergothioneine may help people in their 30s and 40s stay just as fit as they were in their twenties. This is suggested by an animal study published in Cell Metabolism in 2025.

Study
The article published in Cell Metabolism by researchers from the German Leibniz Institute for Analytical Sciences is more than just an animal study. In their publication, the researchers describe a series of animal and in vitro studies through which they uncover a previously completely new mechanism of action of ergothioneine.

The researchers were able to conduct this research because their institute possesses the technology and expertise to record sulfur chemical reactions.

Ergothioneine contains a sulfur atom that plays a key role in the mechanism elucidated by the Germans.

Mechanism
The figures below show a simplified representation of the ergothioneine mechanism. Click on them for a larger version.

The amino acid is used by the enzyme cystathionine gamma-lyase [CSE] as a precursor for hydrogen sulfide.

Hydrogen sulfide [H2S] can react with the cysteine ​​units in enzymes such as cytosolic glycerol-3-phosphate dehydrogenase [cGPDH]. This reaction is called persulfidation. Persulfidation makes enzymes more active. In the case of cGPDH, this means that cells start producing more NAD+.

NAD+ is an energy molecule - or a coenzyme, as biochemists prefer to call it. It provides enzymes with energy. Because aging entails the body producing less NAD+, scientists suspect that boosting the concentration of NAD+ is a longevity strategy. [More]

Results
In an animal study, the Germans gave 9-month-old lab rats - if the rats had been humans, they would have been in their thirties - drinking water in which the researchers had dissolved ergothioneine for four weeks.

If the test animals had been adult humans, they would have ingested 25 to 35 milligrams of ergothioneine daily. Test animals in a control group received drinking water without ergothioneine.

After the supplementation period, the researchers had the rats run on a treadmill until they could no longer continue. The animals in the experimental group sustained this longer and covered a greater distance than the rats in the other group. The researchers found more NAD+ in the muscles of the rats in the experimental group. Those muscles of the rats in this group were also slightly larger.

Conclusion
"In conclusion, by unraveling the molecular intricacies of ergothioneine's actions, our research lays the groundwork for further exploration of its clinical applications and therapeutic implications," the Germans summarize.

"Future studies may explore the therapeutic potential of ergothioneine in mitigating age-related conditions and metabolic disorders, with a focus on translational approaches aimed at harnessing its rejuvenating properties for human health."