New Insights into the Benefits of NMN: Extended Longevity and Improved Intestinal Health in Aging Mice
In May 2024, a landmark study focusing on the effects of β-nicotinamide mononucleotide (NMN) on longevity and gut function health in aging mice was published.
This research provides new insights into how NMN can help slow the aging process and improve overall health. 
Figure 1: The Longevity and Vulnerability Indices of Zmpste24-/- Mice after NMN Treatment.
In the first figure of the study, Zmpste24-/- mice, genetically engineered to age at an accelerated rate, were treated with NMN.
The mice were dosed every other day via oral administration with PBS or NMN (100/300 mg kg-1) until natural death, starting at 5-7 weeks of age.
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.
- Intestinal 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 mucosal cup cells, contributing to improved mucosal barrier function.
Moreover, NMN increases the expression of anti-inflammatory factors and decreases intestinal permeability. - Gene Expression and Cell Activity: NMN increases the expression of genes such as SIRT1, NMNAT2 and NMNAT3, which are involved in aging processes.
It decreases the expression of the P53 protein, which is associated with cell aging, and stimulates the activity of intestinal stem cells (ISCs) through the Wnt/β-catenin signaling pathway, which contributes to intestinal tissue regeneration. - 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, indicating 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 intestinal health and decreases 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
The second figure examined how NMN affects the integrity of the intestinal epithelial barrier and the expression of aging-related genes in aging mice.
C57BL/6 mice were dosed 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 decreased 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 extend 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 thus has potential as a means to promote healthy aging and reduce aging-related intestinal problems.
Future Research
The research suggests that further studies are needed to better understand the specific mechanisms by which NMN regulates 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.
