Nicotinamide adenine dinucleotide (NAD+) exists in all living organisms and is well known as a coenzyme in oxidation−reduction reaction.  Recent research has drawn attention to its relation to “sirtuin” represented by NAD+−dependent protein deacetylases, which is to regulate various life phenomena as aging, people are especially paying high attention to “Anti-aging effect”. The turnover of the oxidized form of nicotinamide adenine dinucleotide (NAD+) has attracted interest in regard to longevity. Meanwhile, sirtuin is NAD+−dependent and increase of cellular NAD+ level is expected to have similar effects to the STACs, thus nicotinamide mononucleotide, an intermediate of NAD+ biosynthesis, is also in the spotlight [1].

Nicotinamide mononucleotide (NMN) has been shown to enhance NAD+ biosynthesis and ameliorate various pathologies in mouse disease models. In this study, researchers conducted a 12-month-long NMN administration to regular chow-fed wild-type mice during their normal aging (scheme 1). Orally administered NMN was quickly utilized to synthesize NAD+ in tissues. Remarkably, NMN effectively mitigates age-associated physiological decline in mice. Without any obvious toxicity or deleterious effects, NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile, and ameliorated eye function and other pathophysiologies. Consistent with these phenotypes, NMN prevented age-associated gene expression changes in key metabolic organs and enhanced mitochondrial oxidative metabolism and mitonuclear protein imbalance in skeletal muscle. These effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective anti-aging interventions in humans [2].

NMN proved to be effective in treating high fat diet-induced type 2 diabetes, which is a chronic and progressive disease with continuously increasing prevalence and rising financial pressure on the worldwide healthcare systems. Recently, the insulin resistance, hallmark of type 2 diabetes, was cured in mice treated with NAD+ precursor β-nicotinamide mononucleotide (NMN), no toxic effects being reported.  NAD+ is present in all living organisms and is a well-known coenzyme in oxidation-reduction reactions. NAD+−dependent protein deacetylases such as SIRT1 and SIRT6 serve as metabolic sensors, and regulate downstream pathways, which eventually restore mitochondrial function and insulin sensitivity [3]. The low cost of the growing media, simple and inexpensive process equipment required may lead to a price reduction of NMN to a level suitable for treating type 2 diabetes and aging related diseases in humans. This finding extends the research domain of NAD+ effects to other degenerative diseases associated with aging, such as: cardiovascular, cancer, arthritis, osteoporosis or Alzheimer’s diseases.

Scheme 1 Control experiment with and without Nicotinamide mononucleotide (NMN)

References

[1] https://www.oyc-bio.jp/products/view/nmn002

[2] Kathryn F. Mills, etc., Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice, Cell Metabolism 24, 795–806, December 13, 2016

[3] George C?t?lin Marinescu, etc., β-nicotinamide mononucleotide (NMN) production in Escherichia coli, 16 August 2018, Scientific RePortS | (2018) 8:12278, 1-11.