β-Nicotinamide Mononucleotide Supplementation Prolongs The Lifespan Of Premature Ageing Mice And Protects Colon Function In Ageing Mice

Ageing is defined as the degenerative process of physiological functions in numerous tissues and organs of an organism that occur with the ageing process. As we ageing, the gut undergoes a series of changes and weaknesses that may contribute to overall ageing. Emerging evidence suggests that β-nicotinamide mononucleotide (NMN) plays a role in regulating intestinal function, but there is still a lack of literature on the colon of ageing mice. In our research the Zmpste24-/- mice proved that NMN prolonged life span and delayed senescence. This study was designed to investigate the effects of a long-term intervention on regulating colon function in ageing mice. Our results indicated that NMN improved the pathology of intestinal epithelial cells and the intestinal permeability by upregulating the expression of intestinal tight junction proteins , the number of goblet cells, increasing the release of anti-inflammatory factors, and increasing beneficial intestinal bacteria. NMN increased the expression of the protein SIRT1, NMNAT2, NMNAT3 and decreased the expression of the protein P53. NMN regulated the activity of ISCs by increasing Wnt/β-catenin and Lgr5. Our findings revealed that NMN exhibit a significant increase in the relative abundance of Akkermansia muciniphila and Bifidobacterium pseudolongum , and notable differences in metabolic pathways related to Choline metabolism in cancer. In summary, NMN supplementation can delay frailty in old age, preserve healthy ageing, and delay gut ageing.

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