20% longer lifespan and improved NAD+ levels

In February 2025, an article was published in Cell Metabolism entitled "Ergothioneine improves healthspan of aged animals by enhancing cGPDH activity through CSE-dependent persulfidation". The goal of the study was to explore the potential effects of ergothioneine supplementation on the healthspan of aged animals and to elucidate the underlying mechanisms driving this effect.

The article indicates that ergothioneine prolongs life span and healthy lifespan in aged Cryptococcus hidradii nematodes and rats, and reveals the mechanism of action of ergothioneine in prolonging life span.

The study tested the effects of ergothioneine on the lifespan of Cryptomeria hidradii nematodes. Treatment with 5 mM ergothioneine from the first day of adulthood significantly prolonged median lifespan by 20%. The ergothioneine-treated nematodes showed a significant increase in mobility, as well as an increase in stress tolerance and a decrease in age-related biomarkers (intestinal autofluorescence, sometimes referred to as lipofuscin or "age pigment").

In addition, the study treated 9-month-old rats (20 mg/kg of ergothioneine in drinking water for 3 weeks), followed by exercise endurance testing. The study found that ergothioneine administration enhanced exercise endurance, muscle mass, and blood vessel formation, along with higher levels of NAD + in the muscle.

Mechanistic studies found that ergothioneine acts as an alternative substrate for the longevity-promoting gene cystathionine gamma-cleaving enzyme (CSE), leading to increased production of hydrogen sulfide (H2S), followed by protein supersulfuration (PSSH). Ergothioneine treatment leads to an increase in mitochondrial respiration, ATP production, and cell growth, accompanied by elevated NAD+ levels in vivo and in vitro. These changes occurred via persulfuration and activation of cytoplasmic glycerol-3-phosphate dehydrogenase (cGPDH), which increased NAD+ levels, resulting in improved muscle mass, vascularization, myocyte stemness, and treadmill endurance in aged rats.

Ergothioneine is a naturally occurring amino acid that was named after a unique crystalline sulfur-containing compound isolated by Charles Tanret in 1909 during his study of the ergot fungus, which destroys rye grain.In 1911, Barger and Ewins determined its structure and found that ergothioneine is a In 1911, Barger and Ewins determined its structure and found that ergothioneine was a histidine betaine derivative. The fact that ergothioneine has both thiol and thione isomers, and that the thione isomer dominates at physiological pH, gives ergothioneine exceptionally strong antioxidant properties. Clinical data show that ergothioneine has 14 times the free radical scavenging capacity of glutathione and 30 times the capacity of coenzyme Q10.

In 2018, Bruce Ames, an American biochemist and professor in the Department of Biochemistry and Molecular Biology at the University of California, defined ergothioneine as a "longevity vitamin" in his article "Prolonging healthy aging: Longevity vitamins and proteins". In his article "Prolonging healthy aging: Longevity vitamins and proteins," Bruce Ames, professor of medicine at the University of California at Berkeley, defines ergothioneine as a "longevity vitamin. And unlike other nutrients in the body, ergothioneine has an exclusive transporter protein, OCTN-1, which can transport ergothioneine directly into the mitochondria for targeted scavenging of free radicals, making it more efficient in combating premature aging. In addition, more and more studies have shown that ergothioneine is a kind of body self-defense "Stress Vitamin", when subjected to stress stimuli (such as starvation, ultraviolet irradiation, metabolic acidosis, etc.), the level of ergothioneine in the organism will increase, and automatically open the body's defense mechanism, to combat stress. against stress.

Based on the characteristics of strong antioxidant, high stability and non-toxicity, ergothioneine has been gradually confirmed by more and more studies that it can play a positive role in human health, in antioxidant, anti-inflammatory, and has a positive effect on skin health, urinary health, intestinal health, cardiovascular system health, prevention of dementia, and improvement of sleep disorders, which has a better application scenario in the fields of biomedicine and beauty and health.

1) Improve cognitive function Oxidative stress is one of the main causes of neurodegenerative diseases. For example, oxidative stress caused by β-amyloid (Aβ) deposition plays an important role in the pathogenesis of Alzheimer's disease. Studies have shown that ergothioneine protects brain health and improves cognitive function, and it can penetrate the blood-brain barrier to enter the brain to do so.

Beginning in 2020, the Japanese market began to introduce functional labeled foods containing ergothioneine, focusing on improving memory function in the elderly, and LS Corporation launched ergothioneine supplements, a product targeting memory decline in middle- and senior-aged seniors.

2) Supporting Skin HealthSkin aging is a multifactorial process that includes aging of the epidermis due to UV radiation, aging of the dermis due to loss of collagen, and inflammation of the sarcoplasmic layer due to apoptosis. Ergothioneine demonstrates significant anti-aging effects at different skin levels through its unique bioactivity: A. Epidermal UV protection: Ergothioneine, as a potent antioxidant, plays an important role in protecting the skin against skin damage caused by UVA and UVB radiation. It protects skin cells from DNA breakage and mutation as well as mitochondrial damage by mitigating the inflammatory response triggered by UV radiation. B. Collagen maintenance in the dermis: In the dermis, ergothioneine enhances collagen synthesis and reduces collagen loss after UV exposure. Studies have shown that ergothioneine significantly improves the viability of fibroblasts, inhibits UV-induced photoaging by reducing matrix metalloproteinase (MMP-1) activity and boosts type I collagen production, reducing collagen damage by as much as 72.9%. C. Cellular Energization and Repair in the Basal Layer of the Skin: In the basal layer of the skin, ergothioneine has a positive effect on cellular energy metabolism, it increases telomerase activity, prolongs cellular energy metabolism and reduces cellular energy metabolism by Increasing telomerase activity, prolonging cell life and promoting rapid renewal and repair of skin tissue.

(3) Eye protectionErgothioneine is present in high concentrations in eye tissues, including lens, retina, cornea and retinal pigment epithelium, and can help protect the eyes by scavenging chronic reactive oxygen radicals (ROS), reducing intracellular ROS production and inhibiting oxidation-induced epithelial mesenchymal transition (EMT).

(4) Sleep Improvement Ergothioneine can penetrate the blood-brain barrier through a variety of biological mechanisms, inhibit the formation of peroxynitrite and nitration of tyrosine residues to impede the apoptosis of brain neuronal cells, thus lowering stress, soothing depression, and improving sleep difficulties.

5) Cardiovascular health studies have shown that ergothioneine can couple glutathione to reduce iron-based myoglobin, chelate transition metal iron to scavenge reactive oxygen species and reactive nitrogen species (ROS/RNS), free radicals, and regulate pro-inflammatory cytokines produced during ischemia-reperfusion.