# Advances in the Synthesis and Physiological Metabolic Regulation of Nicotinamide Mononucleotide
## 4 NMN Regulates Physiological Metabolism
### Other Diseases  
Restoring NAD\({}^{+}\) levels through supplementation with NMN has become a therapeutic approach for the prevention and treatment of various aging-related diseases, with the aim of restoring health and vitality in the elderly (Figure 6). In a mouse model of carotid artery occlusion, exogenous NMN supplementation reduced retinal inflammation and photoreceptor death while activating antioxidant genes and reducing retinal dysfunction in the early retinal detachment phase [143]. NMN can also reduce corneal inflammation caused by hypertonic tears at the early stage of dry eye by regulating the interaction between corneal epithelial cells and macrophages [144]. In a mouse model of acute kidney injury (AKI), NMN treatment significantly reduced renal tubular injury, cellular aging, and renal fibrosis [145]. In another study, NMN was found to increase the levels of NAD\({}^{+}\) and reduce oxidative stress and barrier dysfunction in the gut of aging mice [146]. Similarly, NMN treatment reduced ethanol-induced liver injury in mice by increasing NAD\({}^{+}\) levels, restoring the ERK1/2 pathway, or blocking the overexpression of ATF3 [147]. In summary, NMN seems to indirectly promote healthy aging and ameliorate related disease states by directly increasing NAD\({}^{+}\) levels (Table 2).  
\begin{table}
\begin{tabular}{c c c} \hline \hline
**Research Field** & **Research Progress** & **Reference** \\ \hline DNA repair & NMN increased the telomere length of liver cells in fibrotic mice. & [148] \\  & NMN activated DNA repair proteins, such as PARP1, in aged mice. & [149] \\  & NMN increased insulin sensitivity in mice and humans. & [150] \\ Metabolism & NMN increased the number of mitochondria in the liver of obese mice. & [151] \\  & NMN enhanced the efficiency of energy production in mouse mitochondria. & [152] \\ Cancer & NMN enhanced the efficacy of PD-1-mediated immunotherapy. & [153] \\ Bone repair & NMN improved the cognitive function of mice after chemotherapy. & [154] \\ Cardiovascular & NMN evolved the number of new bone-forming cells in mice. & [155] \\ Eye function & NMN reduced photoreceptor cell death after retinal detachment in mice. & [156] \\ Immunity & NMN enhanced the action of immune T cells and stimulated the production & [158] \\  & of immunoglobulins. & [9] \\ Lifespan & NMN prolonged the lifespan of mice. & [146] \\ Nervous system & NMN improved cognition and memory in a rodent model of Alzheimer’s disease. & [142] \\  & NMN ameliorated depressive behavior in model mice. & [159] \\  & NMN improved the reproductive ability of female mice. & \\ Reproductive system & NMN protected porcine oocytes from cell death due to exposure to & [160] \\  & environmental toxins. & \\ Skin and muscles & NMN promoted muscle remodeling in older individuals. & [161] \\  & NMN reduced liver damage in chronic alcohol intake model mice, reduced renal cell & [162] \\ Organ health & death, and protected the kidneys from ischemic damage. & [163] \\  & NMN promoted the development and differentiation of intestinal stem cells in mice. & \\ \hline \hline \end{tabular}
\end{table}
Table 2: Recent progress on the regulation of physiological metabolism by NMN.  
Figure 6: Potential benefits of NMN supplementation. As a supplemental precursor of NAD+, NMN has a modulating effect on the aging-related deterioration of physical function or diseases, including preventing cognitive decline, improving tissue and organ function, improving metabolic health, reducing inflammation, and increasing physiological benefits, which together may extend a patient’s healthy and overall lifespan.