In May 2024, a groundbreaking study was published focusing on the effects of β-nicotinamide mononucleotide (NMN) on the lifespan and gut health of aging mice. This research offers new insights into how NMN can contribute to slowing the aging process and improving overall health.

Figure 1: The Longevity and Vulnerability Indices of Zmpste24-/- Mice after NMN Treatment.

In the first figure of the study, Zmpste24−/− mice, which are genetically engineered to age prematurely, were treated with NMN. The mice received a dosage every other day via oral administration with PBS or NMN (100/300 mg kg−1) until their natural death, starting at an age of 5-7 weeks. The main findings are as follows:

• Longevity and Health: Supplementation with NMN extends the lifespan of prematurely aged Zmpste24-/- mice and reduces signs of frailty in these mice.
• Gut Health: NMN improves the integrity of the intestinal epithelial barrier, increases the expression of intestinal tight junction proteins such as Claudin1 and the number of goblet cells, which contributes to an improved mucosal barrier function. In addition, NMN increases the expression of anti-inflammatory factors and reduces intestinal permeability.
• Gene Expression and Cell Activity: NMN increases the expression of genes such as SIRT1, NMNAT2, and NMNAT3, which are involved in the aging processes. It reduces the expression of the P53 protein, which is associated with cell aging, and stimulates the activity of intestinal stem cells (ISCs) via the Wnt/β-catenin signaling pathway, which contributes to the regeneration of intestinal tissue.
• Gut Microbiome: NMN supplementation leads to an increase in beneficial gut bacteria such as Akkermansia muciniphila and Bifidobacterium pseudolongum. There are significant changes in metabolic pathways, including choline metabolism in cancer, suggesting an improvement in gut health.
• Fecal Metabolites: Analysis of fecal metabolites shows that NMN significantly alters the composition of fecal metabolites. NMN increases the levels of certain metabolites associated with improved gut health and reduces the levels of metabolites associated with aging.

Figure 2: NMN Restored the Integrity of the Epithelial Layer of the Large Intestine and the Expression of Aging-Related Genes in Aging Mice

In the second figure, it was investigated how NMN affects the integrity of the intestinal epithelial barrier and the expression of aging-related genes in aging mice. C57BL/6 mice received a dosage every other day via oral administration with a vehicle or NMN (300 mg kg−1) until sacrifice, starting at 10 months of age. The main findings are:

• Weight gain: The mice receiving NMN showed significant weight gain compared with the control group.
• Histological Analysis: Histological analysis showed that NMN improves the integrity of the intestinal epithelial barrier and increases the number of mucosal cup cells, contributing to improved mucosal barrier function.
• Gene Expression: NMN increased the expression of anti-inflammatory factors such as Il-10, as well as the expression of genes such as SIRTs, NMNAT1, NMNAT2, and NMNAT3. It also reduces the expression of the P53 protein.
• Western Blot Analysis: Western blot analysis showed that NMN increases the protein levels of Claudin1, SIRT1, NMNAT2 and NMNAT3, contributing to the improvement of intestinal health.

Conclusion

The study concludes that NMN supplementation can prolong lifespan and improve gut health in aging mice. This is achieved by improving the integrity of the intestinal epithelial barrier, regulating gene expression and cell activity, stimulating intestinal stem cells, and improving the composition of the gut microbiome and fecal metabolites. NMN therefore has potential as a means to promote healthy aging and reduce age-related intestinal problems.

Future Research

The research suggests that further studies are needed to better understand the specific mechanisms by which NMN regulates the various aspects of gut health. In addition, it is important to further investigate the interactions between NMN and gut bacteria, as well as the role of autophagy in the processes regulated by NMN.

Source

Gu, Y., Gao, L., He, J., Luo, M., Hu, M., Lin, Y., … & Yu, Y. (2024). β-Nicotinamide mononucleotide supplementation prolongs the lifespan of prematurely aged mice and protects colon function in ageing mice. Food & Function, 15, 3199-3213.