Highlights

  • Animal studies show NMN restores lifespan in premature aging models and improves inflammation and metabolic functioning.
  • Human studies confirm that NMN boosts blood nicotinamide adenine dinucleotide (NAD+) levels, improves markers of healthy metabolism, alleviates fatigue, and enhances physical performance during aging.
  • Future NMN research challenges include determining whether the molecule is the best at boosting NAD+ along with quantifying the exact extent of its lifespan-extending capabilities.

Successfully managing communicable diseases during the 20th century has resulted in significant average lifespan increases. Along those lines, the global number of people over age 65 is expected to reach 1.6 billion by 2050, up from 771 million in 2022. Finding easily administered and accessible treatments to counter physiological ravages that occur during aging has become a paramount endeavor for a number of researchers.

Published in Aging and Disease, Wu and colleagues from Shanghai Jiao Tong University in China review the current state of NMN research, highlighting its potential anti-aging benefits. The researchers describe animal studies showing NMN alleviates age-associated diseases linked to longevity and metabolic impairments. The group also surveys human studies showing that, as expected, NMN effectively increases blood NAD+, improves insulin sensitivity, reduces fatigue, and improves physical function. Wu and colleagues also illuminate some NMN research challenges like the high cost of producing the molecule. This review article provides a crucial and comprehensive investigation of previous NMN research that will help for the planning of future NMN studies, all the while remaining cognizant of current research challenges.

NMN Improves Metabolism, Reduces Inflammation, and Enhances Physical Function

To begin their investigation of NMN’s potential anti-aging benefits, Wu and colleagues performed a thorough literature review of animal model research using NMN. Wu and colleagues reviewed a study that utilized an animal model perhaps not as reliable as other models like rodents showing that NMN increases lifespan for a worm model with an accelerated aging condition called Werner syndrome by ~30%. This study, published in 2019, presented some of the first research suggesting that NMN can promote longevity by potentially exerting anti-aging benefits.

(Fang et al., 2019 | Nature Communications) Administering NMN to worms with an accelerated aging condition called Werner syndrome significantly increased their median survival. Median survival improved to ~20 days for Werner syndrome worms treated with NMN (orange line) compared to ~15 days for non-treated Werner syndrome worms (red line).

The researchers also referred to a study showing that NAD+ declines during aging in mice but that NMN restores it to improve the function of the cell’s powerhouse (the mitochondria). They referred to another study showing that NMN improves body weight, insulin sensitivity, and energy expenditure in mice fed a high-fat diet. Further coverage of the studies showed that NMN reverses age-related increased inflammatory gene activation, suggesting NMN’s anti-inflammatory effects. These mouse studies provided researchers with glimmers of hope that NMN can effectively ameliorate age-associated conditions, possibly even in humans.

Wu and colleagues then investigated the current state of human trial research to find whether the promising findings from animal models apply to people. They reviewed a study showing that NMN restores the length of chromosome ends (telomeres), which fray with age, thus correlating with physiological decline. Moreover, they showed that NMN improves metabolic parameters like insulin sensitivity in prediabetic women. Furthermore, another study in older men showed that NMN improves mental and physical fatigue to possibly counter the onset of age-related frailty. All of the clinical trials reviewed in the survey lend credulity that NMN may improve physiological function during aging.

Determining Whether NMN Is the Superior NAD+ Boosting Molecule

A key question remaining for researchers is which NAD+-boosting nutraceutical, whether NMN or another like nicotinamide riboside (NR), is superior to effectively allay the ravages of aging. NMN is a larger molecule, making it not as easily absorbed into cells as NR, however, an NMN transporter (SLC12A8) was identified in the gut of mice that absorbs NMN. This transporter exists in the human gut, also, but whether it performs the same function as the one in mice remains to be studied.

(Rahman et al., 2023 | Aging and Disease) NMN enters the cell as NR which is then converted to NMN within cells or is absorbed through its gut transporter, SLC12A8.