Key Points:
- Ergothioneine supplementation prolongs the lifespan of worms by 20%.
- Supplementation with ergothioneine increases muscle mass and improves the physical performance of middle-aged rats.
- The vital coenzyme NAD+ is increased in the muscle of rats upon treatment with ergothioneine.
In recent years, the quest for longevity has shifted towards not only extending life but also enhancing its quality—what scientists call “healthspan.” A fascinating study published in Cell Metabolism brings new insights into this field, highlighting the potential of a naturally occurring compound, found abundantly in mushrooms, called ergothioneine to significantly improve the healthspan of aged organisms.
Learning From Worms
Microscopic worms called nematodes (C. elegans) are one of the most widely studied animal models due to, among other factors, their short lifespans and ease of genetic manipulation. In their new Cell Metabolism study, Petrovic and colleagues, researchers based in Germany, Serbia, the U.K., France, Italy, and Spain found that ergothioneine prolongs the lifespan of nematodes by 20%.
Initially, it was thought that ergothioneine’s longevity effects arose from its direct antioxidant properties. However, Petrovic and colleagues point out that the antioxidant potential of ergothioneine itself is not strong. Antioxidants need to readily gain or lose electrons to neutralize reactive oxidants — compounds that cause damage to cells and accelerate aging — and ergothioneine does not readily gain or lose electrons.
To examine this conundrum further, the researchers turned to a compound that contributes to the stinky smell of rotten eggs, hydrogen sulfide (H2S). Compounds like ergothioneine are known to decompose into H2S. When inside our cells, H2S can bind to select proteins, change the shape of those proteins, and increase the activity of those proteins.
The researchers found that, in nematodes fed ergothioneine, there was an increase in the binding of H2S to over 300 proteins. These proteins, presumably more active after being bound to H2S, included antioxidant proteins. The findings suggest that ergothioneine indirectly neutralizes reactive oxidants by elevating H2S levels and activating antioxidant proteins.
Petrovic and colleagues also found that ergothioneine interacts with CSE (cystathionine gamma-lyase), one of the three main proteins that produce H2S. Moreover, the life-prolonging effects of ergothioneine disappeared if CSE was disabled in the nematodes through genetic manipulation. These results demonstrate that ergothioneine may prolong lifespan by increasing H2S via the CSE enzyme, at least in worms.
Ergothioneine Boosts NAD+ and Mitigates Muscle Aging
While part of the animal kingdom, nematodes are not as genetically similar to humans as rats. To test the healthspan-promoting effects of ergothioneine on rats, the researchers fed middle-aged rats 20 mg/kg of ergothioneine for three weeks. The rats were then placed onto treadmills to test their physical performance. As a result of ergothioneine treatment, the time it took for the rats to become exhausted from running nearly doubled. The ergothioneine-treated rats also ran nearly double the distance of untreated rats, demonstrating that ergothioneine improves physical performance.
In addition to improving physical performance, ergothioneine treatment led to a significant increase in muscle mass and muscle vascularization. The increase in muscle growth could be attributed to muscle stem cells, which are necessary for muscle growth and were elevated in ergothioneine-treated rats. Importantly, NAD+ (nicotinamide adenine dinucleotide) contributes to muscle vascularization and muscle stem cell health. NAD+ was found to be elevated in the muscles of ergothioneine-treated rats, suggesting that ergothioneine is an NAD+ booster.
How does ergothioneine boost NAD+? The G3P dehydrogenase (GPDH) protein is one of the main regulators of NAD+ regeneration in cells. The researchers discovered a significant increase in H2S-bound GPDH in the muscles of rats treated with ergothioneine, suggesting that ergothioneine boosts NAD+ by increasing GPDH activity. Moreover, they found the precise location of where H2S binds to GPDH, a region also observed in humans. These findings suggest that ergothioneine may potentially boost muscle NAD+ levels in humans.
Implications for Aging and Health
The findings from this research are particularly compelling, offering a new perspective on how dietary components can influence age-related cellular changes. Ergothioneine’s potential to boost NAD+ levels could make it a critical component in dietary supplements aimed at maintaining muscle strength, enhancing vascular health, and improving overall cellular function in the middle-aged and elderly.
Moreover, the study sheds light on the broader implications of ergothioneine beyond mere supplementation. By increasing the understanding of its biological mechanisms, researchers can develop targeted therapies that mimic or enhance its actions, potentially leading to breakthroughs in geriatric medicine and a better quality of life for the aging population.
Future Research and Considerations
While the study presents robust evidence of the benefits of ergothioneine, it also opens up several avenues for further research. Questions about the optimal dosage, long-term effects, and the potential implications of ergothioneine supplementation in different human populations remain to be explored. Additionally, understanding the interaction between ergothioneine and other dietary components could lead to more effective nutritional strategies for aging.
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