Adult stem cells (ASCs) are undifferentiated cells present in a differentiated tissue that are capable of self-renewal and differentiate to form the cells that make up that type of tissue. However, ASCs inevitably undergo senescence with age, often accompanied by abnormal mitochondrial function. Therefore, it is very important to develop an effective anti-aging drug and functional food to delay the aging of ASCs.
In November 2022, a research team from Jilin University explored the effects of NMN supplementation on mitochondrial function and cellular aging. The results showed that NMN supplementation could increase the activity of long-lived protein sirtuin 3 (Sirt3), reduce stem cell senescence and restore mitochondrial function.
1. NMN restores mitochondrial function and reduces aging of old stem cells
Mitochondrial dysfunction hinders ATP production while also exacerbating the production of reactive oxygen species (ROS), harmful compounds that induce oxidative stress and have been shown to promote cellular senescence. With this in mind, the research team investigated whether treating old stem cells with NMN could improve mitochondrial function and limit the increase in senescent cells.
Before treatment, old stem cells had decreased ATP and increased ROS, indicating abnormal mitochondrial function. After treatment, ATP and ROS levels in old stem cells increased, while the number of senescent cells in old stem cells decreased. The results suggest that NMN can restore mitochondrial function to slow down cellular senescence.
2. The beneficial effect of NMN depends on the activation of Sirt3
Sirt3 is a key mitochondrial protein that helps regulate oxidative stress and plays a key role in ATP production. Given Sirt3's involvement in these key processes, the research team tested whether NMN altered Sirt3 activity in old stem cells. Accordingly, Sirt3 activity was significantly higher in old stem cells treated with NMN, highlighting a potential link between Sirt3 activation and the mitochondrial benefits observed after NMN treatment. To further demonstrate whether Sirt3 activation controls the mitochondrial benefits of NMN, the research team examined whether inhibiting Sirt3 protein in old stem cells would reverse the effects of NMN on mitochondria after treatment. The results showed that blocking SIRT3 abolished the effect of NMN, suggesting that the effect of NMN is mediated by Sirt3.
Collectively, NMN supplementation restored mitochondrial dysfunction and slowed ASCs aging, which provides a promising strategy for the development of antiaging drugs and functional foods.
