How NMN Supplements Can Help Keep You Young: The Basics and Anti-Aging Benefits of This NAD+ Precursor

Rate this article

average: 0 out of 5)

average: 0 out of 5)

Rate this article

PRINT Print
How NMN Supplements Can Help Keep You Young: The Basics and Anti-Aging Benefits of This NAD+ Precursor

Within a few short years in the early 1900s, two seemingly unrelated events took place. In 1902, mysterious symptoms started popping up all over the American South and baffling doctors, including skin rashes, cognitive dysfunction, and confusion. Four years later and some four thousand miles away, two scientists named Harden and Young discovered NAD+ (nicotinamide adenine dinucleotide), originally pinpointing this phenomenon as a compound that enhanced yeast fermentation rates. 

Southern doctors did not yet know, and wouldn’t fully understand until three decades and multiple missteps later, that these debilitating symptoms commonly affecting lower-income individuals were directly related to NAD+ — or lack thereof. Known as pellagra (“rough skin” in Italian), this diet-related disease is caused by inadequate intake of an NAD+ precursor called niacin, or vitamin B3 (found in high amounts in meat, milk, and brewer’s yeast.) Although it would take many more years to fully put these pieces together, it was becoming clear that NAD+ was not just needed for yeast fermentation — it was necessary for human life, too. 

So, what do these century-old stories have to do with aging? As it turns out — a whole lot. From its early pellagra-fighting public health days to later years in lab research worldwide, scientists have shown just how vital NAD+ is to health and longevity. However, NAD+ levels tend to decline as we grow older, accelerating aging and disease. But, there are ways to combat this decline, including one NAD+ precursor called nicotinamide mononucleotide (NMN). As NMN supplements are becoming more popular for health and longevity, you may wonder what the research behind these anti-aging supplements is — let’s take a closer look. 

The ABCs of NAD+

NAD+ is a molecule known as a coenzyme, meaning it helps other enzymes to function properly. Without NAD+, hundreds of life-giving reactions would not be able to take place — both on a larger-level scale, like pumping blood through the body, and the microscopic, like repairing damaged DNA or helping our cell’s mitochondrial powerplants generate energy from food. So, it’s safe to say that NAD+ is a vital part of our daily lives. 

And, NAD+ is not only required for maintaining life but also for having a long life. However, as it turns out, most people experience a drop in NAD+ activity as they age. Some research has found that levels of this crucial coenzyme can drop by as much as 50% between the ages of 40 and 60, with an additional decline upon reaching older age.

Concurrently with this drop in NAD+ increases in signs of accelerated aging or physiological decline — the dysfunctional ​​changes that can occur across all organ systems and contribute to disease states. 

Now for some good news: researchers have found that the compound NMN acts as a direct precursor to NAD+, combating both the age-related decline in NAD+ and the detrimental health outcomes that come along with it.

Concurrently with this drop in NAD+ increases in signs of accelerated aging or physiological decline — the dysfunctional ​​changes that can occur across all organ systems and contribute to disease states.

Is NMN an Anti-Aging Supplement?

Although it was discovered way back in 1963, interest in NMN as an anti-aging supplement didn’t hit the longevity research scene until about a decade ago. With Drs. David Sinclair and Shin-ichiro Imai at its helm, NMN research with lab animals came to the forefront in the early-to-mid 2010s, starting with studies that showed NMN to extend lifespan and improve blood sugar control in mice. 

Since then, NMN has been studied for its anti-aging properties in various body systems. From the external signs of aging, like wrinkled skin and greying hair, to internal characteristics, like cognitive decline and cellular dysfunction, NMN may help to support a healthier aging process. Although much of this research has been done with animals or in cell-based lab settings, studies of humans taking NMN are, slowly but surely, growing too. 

How NMN Can Keep You Young: The Top Anti-Aging Benefits of NMN 

1. Lengthens Lifespan in Lesser Species

Although we don’t have evidence from human studies — yet — research has shown that boosting NAD+ levels through precursors like NMN extends lifespan in lesser species, like yeast and worms. For example, one 2013 study published in Cell found that both NMN and another NAD+ precursor, nicotinamide riboside (NR), extended the lifespan of the commonly studied lab worm, C. elegans, by over 10%. 

However, the research on NMN and lifespan in rodents and humans is still lacking. We will need additional studies before we can state definitively if NMN can lengthen lifespan in humans. 

2. From Sirtuins to Senescence 

One group of enzymes that is dependent on NAD+ are the sirtuins, a family of seven proteins (SIRT1-SIRT7) that play a vital role in aging and longevity. Unfortunately, as NAD+ levels drop with age, the functioning of sirtuins declines right alongside it. 

From repairing damaged DNA to supporting antioxidant pathways to boosting mitochondrial activity, sirtuins are highly involved in many of the key processes regulating aging. However, when sirtuin activity drops, these processes can become dysfunctional and lead to aging or disease. Therefore, supporting your body’s NAD+ levels as you age — with NAD+ precursors like NMN or NR — is essential for healthy sirtuin function, which, in turn, keeps your anti-aging activity flowing smoothly. 

Another way that NMN may help to fight aging is by preventing cellular senescence. Simply put, senescence is when cells stop dividing and lose their function but remain in the body. This irreversible growth arrest causes these zombie-like cells to leave a trail of inflammatory debris in their wake, accelerating aging and causing additional inflammation. One way to slow this process may be by boosting NAD+, as seen in a 2016 study that found restoring mitochondrial NAD+ levels in human stem cells to delay senescence and extend the lifespan of the cells.

3Brain-Boosting Benefits 

A crucial component of feeling young relies on the sharpness of our memory and cognition. Although poor cognition is multifaceted, the symptoms of confusion and cognitive decline that arose in pellagra patients in the 1900s lead us to believe that a reduction in brain NAD+ levels may be one culprit — and NMN may be able to help. 

One 2019 study found that older mice who received supplemental NMN had improvements in memory, gait coordination, and neurovascular health — the network of blood vessels in our brains that are highly involved in cognition. Similarly, a 2020 study reported that NMN improved the health and integrity of both the neurovascular system and the brain as a whole in a group of aged mice, which an uptick in SIRT1 activity may have mediated.

NMN shows brain-supporting benefits

4. Supporting Skin

From wrinkles to sun damage to age spots, our skin takes the brunt of the damage from UV exposure, contributing largely to external aging. Although some people don’t mind these outward signs of aging on their skin, many others do — and one way to support skin health may be by boosting NAD+ levels. 

One recent study found that a combination of NMN and probiotic bacteria could reverse the detrimental effects of skin aging in mice exposed to UVB rays. Adding to the evidence is another paper, authored by scientists in Japan, that found ​​repleting lost NAD+ in UV-exposed skin cells with NMN or NR preserved skin cell integrity and energy production and protected the cells from damage.

5. Fighting Frailty 

Lastly, a common concern amongst aging adults is reduced mobility, which can arise from changes in body composition that cause loss of muscle mass and strength. Not only does this reduction in muscle strength impact mobility, but it also can cause a decline in quality of life, a loss of independence, and an increased risk of mortality.

Once again, a drop in NAD+ levels parallels the typical age-related decline in muscle mass, leading researchers to target NAD+ precursors for fighting frailty. In a 2021 study published in Cell Reports, supplemental NR was found to restore mitochondrial function and muscle integrity in worms, mice, and human cells. Although we don’t know for sure if these results will translate to aging humans with declining muscular function, these species-spanning results are promising.  

Another aspect of physical health that can decline with age is our aerobic capacity — a measure of how well the cardiovascular system can deliver oxygen to muscles — with estimates of a 15% reduction per decade once we reach our 50s. Recent research out of Guangzhou Sport University provided the first-of-its-kind evidence that combining NMN with exercise supports aerobic function in humans. 

The results were found to have a dose-dependent manner. This means that more NMN produced a more significant effect — while the lower dose of NMN (300 mg/day) still exhibited aerobic-boosting benefits, they were about half that of the highest dose group (1200 mg/day). Although this study was done with young- to middle-aged adults, the results are promising for potentially translating to supporting older adults with diminished physical function.

Can NMN Supplements Help Turn Back Time? 

While the anti-aging evidence on NMN and other NAD+ precursor compounds is undoubtedly exciting, this area of research is still in its infancy. However, recent papers have shown that NMN is safe for human consumption, and clinical studies of its use in humans are growing rapidly. So, while we can’t say for sure yet if NMN supplements will turn back the aging clock, the available evidence thus far is certainly encouraging.  

Show references
 

Hong W, Mo F, Zhang Z, Huang M, Wei X. Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Front Cell Dev Biol. 2020;8:246. Published 2020 Apr 28. doi:10.3389/fcell.2020.00246

Irie J, Inagaki E, Fujita M, Nakaya H, Mitsuishi M, Yamaguchi S, Yamashita K, Shigaki S, Ono T, Yukioka H, Okano H, Nabeshima YI, Imai SI, Yasui M, Tsubota K, Itoh H. Endocr J. 2020 Feb 28;67(2):153-160. DOI: 10.1507/endocrj.EJ19-0313. Epub 2019 Nov 2. PMID: 31685720.

Katayoshi T, Nakajo T, Tsuji-Naito K. Restoring NAD+ by NAMPT is essential for the SIRT1/p53-mediated survival of UVA- and UVB-irradiated epidermal keratinocytes [published online ahead of print, 2021 Jun 12] . J Photochem Photobiol B. 2021;221:112238. doi:10.1016/j.jphotobiol.2021.112238

Kiss T, Nyúl-Tóth Á, Balasubramanian P, et al. Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice. Geroscience. 2020;42(2):527-546. doi:10.1007/s11357-020-00165-5

Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr. 2021;18(1):54. Published 2021 Jul 8. doi:10.1186/s12970-021-00442-4

Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. doi:10.1371/journal.pone.0042357

Mills KF, Yoshida S, Stein LR, et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016;24(6):795-806. doi:10.1016/j.cmet.2016.09.013

Mouchiroud L, Houtkooper RH, Moullan N, et al. The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell. 2013;154(2):430-441. doi:10.1016/j.cell.2013.06.016

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;34(12):2840-2851. doi:10.1002/stem.2460

North BJ, Rosenberg MA, Jeganathan KB, et al. SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. EMBO J. 2014;33(13):1438-1453. doi:10.15252/embj.201386907

Poddar SK, Sifat AE, Haque S, Nahid NA, Chowdhury S, Mehedi I. Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule. Biomolecules. 2019;9(1):34. Published 2019 Jan 21. doi:10.3390/biom9010034

Tarantini S, Valcarcel-Ares MN, Toth P, et al. Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses. Redox Biol. 2019;24:101192. doi:10.1016/j.redox.2019.101192

Yoshino J, Baur JA, Imai SI. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018;27(3):513-528. doi:10.1016/j.cmet.2017.11.002

Zhou X, Du HH, Ni L, et al. Nicotinamide Mononucleotide Combined With Lactobacillus fermentum TKSN041 Reduces the Photoaging Damage in Murine Skin by Activating AMPK Signaling Pathway. Front Pharmacol. 2021;12:643089. Published 2021 Mar 25. doi:10.3389/fphar.2021.643089

Rate this article

Rate this article

Share This Article

Share your Comments
Enrich and inform our Longevity Community. Your opinion matters!