Supplementation with Nicotinamide Mononucleotide (NMN) has preventive and therapeutic effects against age-associated functional decline and common ailments of aging. Even though science has improved our understanding of the progressive decline in function our bodies experience because of aging, there is not yet a clear mechanism that can explain why chronic diseases are an inherent part of the aging process. We expect to live longer lives, but our quality of life is affected by age-related diseases.
Maintaining Cellular Energy Levels at Youthful levels
Many of these age-related impairments have common roots at the cellular level and can be traced back to deficits in the production of cellular energy. NMN has an important effect on the production of cellular energy because it is a critical component in the production of NAD+. Levels of NAD+ are of critical importance for keeping mitochondria, the body’s powerhouse, working at peak, youthful levels. Because of its importance as a NAD+ intermediate, active supplementation with NMN increases the concentration of NAD+ in the body, providing a readily available supply of this important nutrient for the amelioration of age-associated diseases and conditions. As we get older, NAD+ levels consistently decline, energy production is less efficient, and the aging process gains momentum, which contributes to the development of many of the “typical” diseases of aging. 1
When it comes to the production of NAD+, no other nutrient is more important than NMN. In fact, NMN is considered to be the rate-limiting biosynthetic enzyme for the production of NAD+, not only in humans, but in all mammals. Multiple studies have demonstrated that supplementation with NMN promotes the biosynthesis of NAD+ across organs such as the pancreas, liver, muscle, kidneys, eyes, and blood vessels. 2-7
Countering Age Related Metabolic Decline
The effects if NMN supplementation go beyond just the increased production of NAD+. Studies done in rodents have shown that NMN improves glucose tolerance in aging mice who developed diabetes because of high-sugar diets. These findings suggest similar effects might be possible in older humans who develop diabetes because of a poor diet. 3, 8 Further studies have demonstrated the benefits of NMN supplementation for improving sugar metabolism as we age. NMN increases the production of insulin, when insulin-resistance has been caused by a high-fat diet. This is achieved by restoring adequate production of NAD+ and by reducing inflammation and stress caused by free radical damage, countering the effects of age-related chronic inflammation. 3 These studies have also shown that NMN reduces inflammation in fatty tissue, and improves sensitivity to insulin across several different organs. 9 Most importantly, these beneficial effects were found to be more effective in old age.
Keeping Circulation Young
Subscribe to the World's Most Popular Fibromyalgia Newsletter (it's free!)
The circulatory system carries blood rich in oxygen, exchanges heat and nutrients, and removes waste from all the organs and systems in the body. The aging process may lead to chronic changes that diminish the density of the blood vessels that compromise this system. This decline in blood flow worsens over time and contributes to the occurrence of chronic disease and premature aging. 10 One of the direct consequences of this reduction in blood flow is the loss of muscle mass. This progressive loss of muscle mass is a huge contributor to decreased quality of life in old age due to its impact on performance and loss of mobility. NAD+ precursors such as NMN increase the production and maintenance of blood vessels by repairing damaged DNA at the cellular level, optimizing mitochondrial energy production, and promoting glucose tolerance. 7
Sirtuin deacetylase (SIRT1) is a compound critical for the production and maintenance of new and existing blood vessels. NAD+ precursors such as NMN are an effective way of stimulating SIRT1 activity. 5 Studies done in rodents show that supplementation with NMN has a dramatic effect on the preservation of blood vessels. In one study, NMN was shown to restore the number of blood vessels and increase circulatory density in old mice, effectively reverting circulatory capacity to levels seen in young mice. Remarkably, the mice that received the NMN supplementations demonstrated a 60-80% improvement in muscle endurance. 11
Preserving a Sharp Mind in Old Age
One of the most exciting findings regarding how NMN can promote the production of NAD+, is that administration of NMN was shown to cause an increase of NAD+ production in the brain. 12, 13 Findings from recent studies suggest that NMN may be of benefit for preserving cognitive function and protecting neuronal health. Studies done with models for Alzheimer’s showed that NMN had significant, beneficial effects on memory and cognition. 14, 15 NMN not only is protective against the decline in cognitive abilities associated with old age, but has found to be of value for preservation of neurons after a stroke. 16, 17
Extending Cellular Lifespan
Research into the anti-aging properties of NMN shows that the notion of aging being an irreversible process may no longer be an absolute, experiments done in human stem cells have demonstrated that providing an environment rich in NMN extends the lifespan of these cells by delaying age related decline that is a result of continued cell replication. These anti-aging benefits have been related to NMN’s ability to maintain a high production of NAD+ for production of energy in the cell’s mitochondria. 18
Anti-aging research has shown that supplementation with NMN, a key NAD+ intermediate, is effective at mitigating age-associated metabolic decline and slowing the progression of a multitude of age-related diseases. NMN has beneficial effects on the production of energy at the cellular level, improves tolerance to glucose, reduces inflammation, helps preserve the circulatory system, repairs DNA, and has beneficial effects on the preservation of cognitive function. NMN has also shown potential as a therapeutic agent against Alzheimer’s disease and other neurodegenerative disorders typical of old age. Supplementation with NMN may be of benefit in preserving endurance and mobility. Preserving the functions of these diverse systems across the body promotes health and longevity and significantly improves quality of life as aging progresses.
1. Canto, C., Menzies, K.J., and Auwerx, J. (2015). NAD(+) metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell Metab. 22, 31–53.
2. Guan, Y., Wang, S.R., Huang, X.Z., Xie, Q.H., Xu, Y.Y., Shang, D., and Hao, C.M. (2017). Nicotinamide mononucleotide, an NAD+ precursor, rescues age-associated susceptibility to AKI in a sirtuin 1-dependent manner. J. Am. Soc. Nephrol. 28, 2337–2352.
3. Yoshino, J., Mills, K.F., Yoon, M.J., and Imai, S. (2011). Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 14, 528–536.
4. Peek, C.B., Affinati, A.H., Ramsey, K.M., Kuo, H.Y., Yu, W., Sena, L.A., Ilkayeva, O., Marcheva, B., Kobayashi, Y., Omura, C., et al. (2013). Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342, 1243417.
5. Gomes, A.P., Price, N.L., Ling, A.J., Moslehi, J.J., Montgomery, M.K., Rajman, L., White, J.P., Teodoro, J.S., Wrann, C.D., Hubbard, B.P., et al. (2013). Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155, 1624–1638.
6. Lin, J.B., Kubota, S., Ban, N., Yoshida, M., Santeford, A., Sene, A., Nakamura, R., Zapata, N., Kubota, M., Tsubota, K., et al. (2016). NAMPT-mediated NAD (+) biosynthesis is essential for vision in mice. Cell Rep. 17, 69–85.
7. de Picciotto, N.E., Gano, L.B., Johnson, L.C., Martens, C.R., Sindler, A.L., Mills, K.F., Imai, S., and Seals, D.R. (2016). Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell 15, 522–530.
8. Caton, P.W., Kieswich, J., Yaqoob, M.M., Holness, M.J., and Sugden, M.C. (2011). Nicotinamide mononucleotide protects against pro-inflammatory cytokine-mediate impairment of mouse islet function. Diabetologia 54, 3083–3092.
9. Stromsdorfer, K.L., Yamaguchi, S., Yoon, M.J., Moseley, A.C., Franczyk, M.P., Kelly, S.C., Qi, N., Imai, S., and Yoshino, J. (2016). NAMPT-mediated NAD(+) biosynthesis in adipocytes regulates adipose tissue function and multi-organ insulin sensitivity in mice. Cell Rep. 16, 1851–1860.
10. Le Couteur, D.G., and Lakatta, E.G. (2010). A vascular theory of aging. J. Gerontol. A Biol. Sci. Med. Sci. 65, 1025–1027
11. Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Sinclair, D. A. (2018). Impairment of an Endothelial NAD + -H 2 S Signaling Network Is a Reversible Cause of Vascular Aging. Cell, 173(1), 74–89.e20. doi:10.1016/j.cell.2018.02.00
12. Stein, L.R., and Imai, S. (2014). Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging. EMBO J. 33,1321–1340.
13. Yoon, M.J., Yoshida, M., Johnson, S., Takikawa, A., Usui, I., Tobe, K., Nakagawa, T., Yoshino, J., and Imai, S. (2015). SIRT1-mediated eNAMPT secretion from adipose tissue regulates hypothalamic NAD(+) and function in mice. Cell Metab. 21, 706–717.
14. Wang, X., Zhang, Z.F., Zheng, G.H., Wang, A.M., Sun, C.H., Qin, S.P., Zhuang, J., Lu, J., Ma, D.F., and Zheng, Y.L. (2017). The inhibitory effects of purple sweet potato color on hepatic inflammation is associated with restoration of NAD(+) levels and attenuation of NLRP3 inflammasome activation in high-fat-diet-treated mice. Molecules 22, https://doi.or 3390/molecules22081315.
15. Yao, Z., Yang, W., Gao, Z., and Jia, P. (2017). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease. Neurosci. Lett. 647, 133–140.
16. Park, J.H., Long, A., Owens, K., and Kristian, T. (2016). Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically amelioratesbrain damage following global cerebral ischemia. Neurobiol. Dis. 95, 102–110.
17. Wei, C.C., Kong, Y.Y., Li, G.Q., Guan, Y.F., Wang, P., and Miao, C.Y. (2017a). Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway. Sci. Rep. 7, 717
18. Son MJ, Kwon Y, Son T, Cho YS. Restoration of Mitochondrial NAD+ Levels Delays Stem Cell Senescence and Facilitates Reprogramming of Aged Somatic Cells. Stem Cells. 2016 Dec; 34(12):2840-2851. doi: 10.1002/stem.2460. Epub 2016 Jul 22