Fathoming Out the Role of NMN in Maintaining the Colon Health of Ageing Mice

Fathoming Out the Role of NMN in Maintaining the Colon Health of Ageing Mice



Introduction

The gut is a diverse and dynamic microbiotic system. There are about 100 trillion microorganisms in the gut, which is mainly composed of anaerobic, partially anaerobic, and aerobic bacteria. In the process of ageing, the intestinal tract may show an increase in the permeability of the epithelial barrier and impaired tight junction proteins. Notably, supplementing β-Nicotinamide mononucleotide (NMN) to elevate NAD+ level has been proved to prolong life and maintain the colon health in ageing Mice.

Research protocol

Zmpste24−/− mice are frequently used in the construction of the prematurely ageing model, due to their features of slow weight gain, malnutrition and progressive hair loss, with a short median survival of about 20 weeks. Herein, to fathom out the role of NMN in maintaining the colon health of ageing mice, Zmpste24−/− mice aged 5-7 weeks are orally gavaged with phosphate-buffered saline (PBS), or NMN at 100/300 mg kg−1 every other day until natural death. Likewise, natural ageing C57BL/6 mice aged 10 months old are subjected to the oral gavage of PBS or NMN at 300 mg kg−1, serving as the the control. During experiments, the body weight of mice is recorded, and their frailty index and fecal samples are detected.

The life span and frailty indices in Zmpste24-/- mice after NMN treatment

NMN extends the healthy and median lifespan of Zmpste24−/−improves the Zmpste24−/− ageing phenotype. Specifically, the median lifespan of the mice is increased from 21.4 weeks to 25.7 weeks post NMN intervention, with more than 20% growth. Also, NMN effectively increases body weight. Meanwhile, mice have better overall health after NMN treatment, as manifested by the slowly increasing trend towards Sinclairs frailty indices.

The role of NMN in the intestinal tract of ageing mice

NMN adjusts the activity of genes involved in ageing mice colons. Simply put, in the presence of NMN supplement, the protein level of transcriptional regulator P53 is reduced, while the expression levels of ageing marker Sirt1, NMNAT2 and NMNAT3 are elevated.



NMN improves the pathology of intestinal epithelial cells and intestinal permeability, as evidenced by the upregulation of intestinal tight junction protein (Claudin1,) and the number of goblet cells, the elevated release of anti-inflammatory factor (IL-10), and the increasing beneficial intestinal bacteria (Akkermansia muciniphila and Bifidobacterium pseudolongum).




 

Conclusion

NMN supplementation exerts a protective effect on colon mucosa by controlling the activity of genes involved in ageing, intestinal stem cell differentiation and improving intestinal flora homeostasis, which may be a viable strategy for maintaining healthy ageing in the gut.

Reference

Yanrou Gu, Lidan Gao, Jiamin He et al. β-Nicotinamide mononucleotide supplementation prolongs the lifespan of prematurely aged mice and protects colon function in ageing mice. Food Funct., 2024 (15): 3199-3213. DOI: 10.1039/D3FO05221D

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