Beta-nicotinamide mononucleotide (NMN) has been very popular recently, so I checked some relevant literature and found it interesting, so I will share it.
NMN structure
β-Nicotinamide mononucleotide (NMN) is the precursor of a key coenzyme nicotinamide adenine dinucleotide (NAD+) in mammals. Its main function is embodied by NAD+ and participates in many key processes, including energy Metabolism, gene expression and DNA repair.
Figure 1 In vivo NMN to NAD+ pathway
NAD+ is a key coenzyme in cellular energy metabolism and adaptive response to oxidative stress. The NAD+-centered mammalian aging theory believes that NAD+ levels determine the speed and degree of aging.
NAD+ is present in all cells of the human body and is an important cofactor or co-substrate for a variety of enzymatic processes, including glycolysis, the TCA cycle, oxidative phosphorylation, DNA repair, and protein deacetylation.
NAD+ levels are important for maintaining mitochondrial homeostasis, the metabolism of organisms, the normal function of organs and tissues, and delaying aging.
In middle age, the level of NAD+ in the human body will drop to half of that of young people, and exogenous NMN supplementation can increase the level of NAD+ in the body, so NMN supplementation is very helpful to delay aging, and NMN is widely found in natural foods, vegetables, NMN was found in fungi, meat, and shrimp (Table 1).
In addition, another oral experiment showed that when a lower concentration of NMN was taken, NMN could be rapidly absorbed within 30 minutes, effectively transported to the blood circulation, and immediately converted into NAD+ in the main metabolic tissues.
Wang Huan studied the effect of NMN on mitochondrial function and cell senescence of aging MSCs, MSCs: mesenchymal stem cells. Master's thesis: NMN improves mitochondrial function and inhibits senescence of mesenchymal stem cells through NAD+/Sirt3 pathway
In order to explore whether NMN , the precursor of NAD+, can improve the mitochondrial function of senescent MSCs, 100 μM NMN was added to senescent MSCs (LPMSCs, LP), and Mito-Tracker Red (MTR) fluorescence staining was performed 24 h later.
The results are shown in Figure 2. The mitochondria in the LP group were scattered and fragmented, while the mitochondria in the LP+NMN group were concentrated, indicating that NMN could make the mitochondrial morphology of aging MSCs tend to be normal.
Figure 2 The effect of NMN on the mitochondrial morphology of senescent MSCs (MTR fluorescence staining observed mitochondrial morphology)
To investigate whether NMN affects mitochondrial function? The researchers also tested the content of ATP (adenosine triphosphate, a coenzyme, which has the effect of improving the body's metabolism and is involved in the metabolism of fat, protein, sugar, nucleic acid and nucleotides in the body) and ROS (reactive oxygen free radicals).
The results showed that compared with the LP group, the intracellular ATP content in the LP+NMN group was significantly increased (P<0.05, Figure 3A), while the ROS level was significantly decreased (P<0.001, Figure 3B). The results of JC-1 staining showed that the red fluorescence of mitochondria in the LP+NMN group was stronger and the green fluorescence was weaker, that is, NMN increased the mitochondrial membrane potential of senescent MSCs (Fig. 4A); flow cytometry detection also obtained
Consistent results (Fig. 4B). Therefore, NMN can effectively improve the mitochondrial function of aging MSCs.
Figure 3 Effects of NMN on ATP content and ROS level in aging MSCs
Figure 4 The effect of NMN on mitochondrial membrane potential of senescent MSCs.
A: JC-1 staining showed that the mitochondrial membrane potential of cells in the LP+NMN group was increased.
B: Flow cytometry to detect mitochondrial membrane potential.
In order to explore whether the effect of NMN is related to intracellular NAD+ content and NAD+/NADH ratio, the intracellular NAD+ content and NAD+/NADH ratio after NMN treatment were measured.
As shown in Figure 5, compared with the LP group, the intracellular NAD+ content in the LP+NMN group was significantly increased (P<0.001), and the ratio of NAD+/NADH was also significantly increased (P<0.01). That is, NMN may exert its regulatory effect on mitochondrial function and MSCs aging by up-regulating NAD+ content and NAD+/NADH ratio.
Fig. 5 Effects of NMN on NAD+ content and NAD+/NADH ratio in senescent MSCs. A: The detection results of NAD+ content showed that the intracellular NAD+ content of LP+NMN group increased. B: The measurement results of NAD+/NADH ratio showed that the intracellular NAD+/NADH ratio of LP+NMN group increased summary
1. Compared with young MSCs (bone marrow mesenchymal stem cells), the morphology of aging MSCs changed significantly, the cells were spread, the boundaries became blurred, the three-dimensional sense was lost, the surface area increased and the aspect ratio decreased;
2. Mitochondrial dysfunction in aging MSCs, manifested as: mitochondrial distribution is scattered, and fragmentation is obvious; the content of ATP in aging MSCs decreases and the production of ROS increases;
3. NMN changed the cell morphology of senescent MSCs, decreased the surface area and increased the aspect ratio; NMN could improve the mitochondrial function of senescent MSCs, the mitochondrial distribution became concentrated, the content of ATP in senescent cells increased, and the level of ROS decreased;
4. NMN can improve the mitochondrial function of senescent MSCs and inhibit the senescence of MSCs. This regulation is achieved by up-regulating the intracellular NAD+ content and Sirt3 (mitochondrial NAD+-dependent deacetylase) expression.
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