How NAD+ and Ergothioneine Contribute to Exceptional Longevity
Recently, a study published on bioRxiv revealed the metabolic secrets behind the remarkable longevity of centenarians. Led by Boston University, the research conducted metabolomic analyses on 213 participants—including 70 centenarians, 80 offspring of centenarians, and 63 control individuals. The study discovered unique metabolic characteristics in centenarians, with the NAD+ metabolic pathway and the role of ergothioneine being particularly prominent.
Using untargeted serum metabolomics techniques, the researchers analyzed more than 1,400 metabolites. The results showed that bile acid metabolism in centenarians is unusually active, with significantly elevated levels of both primary and secondary bile acids, such as increased concentrations of cholic acid and lithocholic acid. Meanwhile, levels of biliverdin and bilirubin were also markedly higher, whereas certain steroid hormone levels remained stable.
These metabolic changes are strongly associated with reduced mortality, suggesting that they may play important roles in slowing the aging process. The study also identified several specific metabolic markers linked with exceptional longevity and confirmed these findings across multiple cohorts totaling 5,128 participants, demonstrating consistent patterns across diverse populations.
NAD+ (nicotinamide adenine dinucleotide) is a central molecule in cellular energy metabolism. The study found that the tryptophan/kynurenine ratio decreases with age—the lower the ratio, the poorer the efficiency of NAD+ synthesis and the higher the level of inflammation.
However, in centenarians, this ratio remains at relatively high levels, indicating a more favorable NAD+ metabolic state. In addition, the aspartate/quinolinic acid ratio is also closely associated with NAD+ metabolism, with higher ratios reflecting healthier metabolic regulation. Multiple age-related metabolic changes consistently point to the pivotal role of NAD+ metabolism in healthy aging.
Ergothioneine is a natural antioxidant commonly found in mushrooms, and animal studies have shown that it has lifespan-extending effects. The research revealed that human ergothioneine levels decline with age, a trend also observed in centenarians.
Interestingly, ergothioneine interacts with the gut microbiota: it can be degraded by bacteria into trimethylamine (TMA), which is then converted into trimethylamine-N-oxide (TMAO). The ergothioneine/TMAO ratio reflects the metabolic activity of gut bacteria: a higher ratio indicates weaker bacterial degradation. This ratio is negatively correlated with uremic toxins, suggesting potential benefits for kidney health.
Based on these findings, maintaining a healthy NAD+ metabolic state is considered a common feature among centenarians. The study highlights that the tryptophan/kynurenine ratio is a key indicator for evaluating NAD+ synthesis efficiency, and this marker performs particularly well in long-lived populations.
This research not only uncovers the unique metabolic profiles of centenarians but also emphasizes the importance of NAD+-related metabolic pathways and ergothioneine in promoting healthy longevity. These insights provide strong scientific foundations for future development and application of NAD+ supplements.
PART 01
Metabolomic Features of Centenarian PopulationsUsing untargeted serum metabolomics techniques, the researchers analyzed more than 1,400 metabolites. The results showed that bile acid metabolism in centenarians is unusually active, with significantly elevated levels of both primary and secondary bile acids, such as increased concentrations of cholic acid and lithocholic acid. Meanwhile, levels of biliverdin and bilirubin were also markedly higher, whereas certain steroid hormone levels remained stable.
These metabolic changes are strongly associated with reduced mortality, suggesting that they may play important roles in slowing the aging process. The study also identified several specific metabolic markers linked with exceptional longevity and confirmed these findings across multiple cohorts totaling 5,128 participants, demonstrating consistent patterns across diverse populations.
PART 02
NAD+: A Key to Maintaining Metabolic VitalityNAD+ (nicotinamide adenine dinucleotide) is a central molecule in cellular energy metabolism. The study found that the tryptophan/kynurenine ratio decreases with age—the lower the ratio, the poorer the efficiency of NAD+ synthesis and the higher the level of inflammation.
However, in centenarians, this ratio remains at relatively high levels, indicating a more favorable NAD+ metabolic state. In addition, the aspartate/quinolinic acid ratio is also closely associated with NAD+ metabolism, with higher ratios reflecting healthier metabolic regulation. Multiple age-related metabolic changes consistently point to the pivotal role of NAD+ metabolism in healthy aging.
PART 03
Ergothioneine: The “Guardian of Longevity” from MushroomsErgothioneine is a natural antioxidant commonly found in mushrooms, and animal studies have shown that it has lifespan-extending effects. The research revealed that human ergothioneine levels decline with age, a trend also observed in centenarians.
Interestingly, ergothioneine interacts with the gut microbiota: it can be degraded by bacteria into trimethylamine (TMA), which is then converted into trimethylamine-N-oxide (TMAO). The ergothioneine/TMAO ratio reflects the metabolic activity of gut bacteria: a higher ratio indicates weaker bacterial degradation. This ratio is negatively correlated with uremic toxins, suggesting potential benefits for kidney health.
PART 04
NAD+ Supplementation: A New Direction for Scientific Anti-AgingBased on these findings, maintaining a healthy NAD+ metabolic state is considered a common feature among centenarians. The study highlights that the tryptophan/kynurenine ratio is a key indicator for evaluating NAD+ synthesis efficiency, and this marker performs particularly well in long-lived populations.
This research not only uncovers the unique metabolic profiles of centenarians but also emphasizes the importance of NAD+-related metabolic pathways and ergothioneine in promoting healthy longevity. These insights provide strong scientific foundations for future development and application of NAD+ supplements.
