Adult stem cells (ASCs) are undifferentiated cells that are present in a differentiated tissue and are capable of self-renewal and differentiation to form the cells that make up that type of tissue. However, ASCs inevitably undergo senescence with age, often accompanied by abnormal mitochondrial function. It is therefore essential to develop an effective anti-ageing drug and functional food to slow down the ageing of ASCs.
In November 2022, a research team from Jilin University published a paper in the International Journal of Molecular Sciences entitled "Nicotinamide Mononucleotide Supplementation Improves Mitochondrial Dysfunction and Rescues Cellular Senescence by NAD+/Sirt3 Pathway in Mesenchymal Stem Cells.
This study explored the effects of NMN supplementation on mitochondrial function and cellular senescence. The results showed that NMN supplementation increased the activity of the longevity protein sirtuin 3 (Sirt3), reduced stem cell senescence and restored mitochondrial function.
1, NMN restores mitochondrial function and reduces senescence in old stem cells
Abnormal mitochondrial function prevents the production of ATP and also increases 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 team investigated whether treating old stem cells with NMN could improve mitochondrial function and limit the increase in senescent cells.
Prior to treatment, old stem cells had reduced ATP and increased ROS, indicating abnormal mitochondrial function. After treatment, ATP increased and ROS levels decreased in the old stem cells, while the number of senescent cells in the old stem cells was reduced. The results suggest that NMN can restore mitochondrial function to slow down cellular senescence.
(NMN increases ATP levels, decreases ROS levels and reduces senescent cells)
2,The beneficial effects of NMN are dependent on the activation of Sirt3
Sirt3 is a key mitochondrial protein that contributes to the regulation of oxidative stress and plays a key role in ATP production. Given that Sirt3 is involved in these key processes, the team tested whether NMN altered the activity of Sirt3 in old stem cells. As a result, Sirt3 activity was significantly higher in old stem cells treated with NMN, highlighting a potential link between Sirt3 activation and the mitochondrial benefits observed following NMN treatment. To further demonstrate whether Sirt3 activation controls the mitochondrial benefits of NMN, the team examined whether inhibition of Sirt3 protein in old stem cells would reverse the mitochondrial effects of NMN after treatment. The results showed that blocking sirt3 abrogated the effects of NMN, suggesting that the effects of NMN are mediated by Sirt3.
(NMN enhances Sirt3 activity)
Overall, NMN supplementation restores abnormal mitochondrial function and slows down the ageing of ASCs, which provides a promising strategy for the development of anti-ageing drugs and functional foods.
