Ergothioneine Mitigates Telomere Shortening under Oxidative Stress Conditions

Shortened telomeres are associated with aging and age-related diseases. Oxidative stress is thought to be a major contributor to telomere shortening, and antioxidants may be able to mitigate these effects. Ergothioneine is a naturally occurring amino acid with potent antioxidant properties. In order to investigate ergothioneine's effects on telomere length, we cultured primary human fibroblasts under standard and oxidative (10 µM H2O2) conditions and treated cells with 0.04, 0.1, 0.3, or 1.0 mg/ml ergothioneine for 8 weeks. Telomere length measurements were performed using high-throughput quantitative fluorescent in situ hybridization (HT Q-FISH). Treatment with ergothioneine transiently increased relative telomerase activity after 24 h (p < 0.05 for all concentrations). Under oxidative conditions, ergothioneine treatment resulted in significantly longer median telomere length and 20th percentile telomere length, and significantly reduced the percentage of short telomeres (<3 kilobase pairs) for all treatment concentrations after 8 weeks. Telomere shortening rate was also reduced. Overall, ergothioneine demonstrated beneficial effects by decreasing the rate of telomere shortening and preserving telomere length under oxidative stress conditions. Our data support a potential role for ergothioneine in oxidative stress-related conditions and healthy aging.