Highlights

  • NMN extends the median as well as the maximum lifespan in a mouse model of premature aging.
  • Supplementing with NMN restores multiprotein complexes that are crucial to intestinal barrier formation — tight junctions — in healthy, middle-aged mice.
  • NMN also beneficially restructures the gut microbial composition — the microbiome — of middle-aged mice.

Published in Food & Function, Yu and colleagues from Wenzhou Medical University in China show that oral NMN extends the average (14%), median (20%), and maximum (10%) lifespans of mice that prematurely age. The researchers also found that NMN restored intestinal tight junction multiprotein complexes, crucial contributors to the intestinal barrier, in healthy, middle-aged mice not undergoing premature aging. Additionally, NMN revamped the abundance of beneficial intestinal bacteria, further highlighting its capabilities to restore gut health.

While other studies have already shown that NMN enhances gut health and improves the microbiome, this is the first to show lifespan extension in fast-aging mice (progeria mice). The findings of lifespan extension in genetically mutant mice that age prematurely may pave the way for future experiments testing whether NMN extends life in healthy, aged mice. Positive lifespan-extension findings using healthy mice would be one of the first steps to trigger research on whether NMN also extends human lifespan.

A 20% Extension on Life for Premature Aging Mice and Boosted Gut Function

Since progeria mice’s lifespan only reaches about five months, compared to healthy mice that live up to 2.5 years, studying their lifespan is more time- and cost-effective. In other words, with their much shorter lifespans, studying NMN’s effects on progeria mice lifespan takes much less time, which requires less cost for laboratory work.

The observation that prematurely aged mice treated with NMN lived a 20% longer median lifespan bolsters the findings in another mouse model that NMN increases amyotrophic lateral sclerosis (ALS) mouse lifespan. In the case of the ALS model mice, median lifespans were only increased by about 3.5%.

In addition to NMN markedly increasing the median lifespan of progeria mice, it also extended the maximum mouse lifespan by about 10%. In contrast, NMN had no effect on maximum lifespan in ALS mice. With these findings in progeria mice, researchers could be more compelled to find whether NMN extends healthy mouse lifespan.

(Gu et al., 2024 | Food & Function) NMN boosts median and maximum lifespan by about 20% and 10%, respectively, in fast-aging mice. Progeria mice given NMN (N300; blue line) exhibited a median lifespan (Median survival) about 20% longer than non-treated mice (PBS; black line). NMN also nearly extended the maximum lifespan of these mice by 10%.

While another previous study showed that NMN increased gene activity for intestinal tight junction proteins (Claudin-1 proteins), Yu and colleagues went a step further by measuring protein levels. They showed that NMN increases levels of these tight junction proteins about fourfold compared to other middle-aged mice not given NMN. These findings corroborate other findings suggesting that NMN restores tight junctions, which are key to establishing a functional barrier between the gut and what enters circulation, in middle-aged mice. Since intestinal dysfunction may contribute to aging and a shorter lifespan, improving the intestinal barrier could be one of the ways that NMN extends life.

(Gu et al., 2024 | Food & Function) NMN increased the abundance of the intestinal gap junction constituent protein Claudin-1 about fourfold. NMN increased intestinal Claudin-1 protein abundance about fourfold (NMN; red bar) compared to non-treated mice (PBS; blue bar).

A healthy microbiome composition is crucial for avoiding digestive problems from age-related gut microbe imbalances — dysbiosis. In that regard, Yu and colleagues identified that NMN increases the abundance of a few beneficial gut bacteria, Bifidobacterium pseudolongum and Akkermansia muciniphila. As such, Bifidobacterium pseudolongum has been shown to possess anticancer properties. Furthermore, elevated Akkermansia muciniphila abundance has been associated with longer-lived individuals who reach 100 (centenarians). By increasing the abundance of these two species in the intestines, NMN may propel a healthier gut during aging.

Determining Whether NMN Extends Healthy, Aged Mouse Lifespan

As with NMN, nicotinamide riboside (NR) is a precursor of nicotinamide adenine dinucleotide (NAD+). NAD+ levels drop with age, and increasing its cellular concentrations with precursors like NMN or NR has been shown to alleviate age-related neurodegenerative, cardiovascular, and metabolic conditions. Interestingly, both NMN and NR have now been shown to extend progeria mouse lifespan. All the same, research has been conducted showing that NR does not extend healthy mouse lifespan.

Yu and colleagues’ findings that NMN extends the lifespan of progeria mice by ~20% offers a clue that it may do so in healthy mice. On the other hand, it could fail to extend healthy mouse lifespan just like NR.

Along those lines, Dr. Rich Miller, who is one of the architects of a consortium that tests potential lifespan-extending interventions in healthy mice (the Interventions Testing Program [ITP]), hints that his team may test NMN soon. In that regard, he says that he is collaborating with private NMN vendors to obtain enough of this supplement to test NMN’s effects on lifespan in healthy mice. If Dr. Miller and colleagues find that NMN does in fact extend healthy mouse lifespan, this would provide some evidence that NMN’s anti-aging effects are superior to NR’s.

Furthermore, if healthy mouse NMN experiments give positive lifespan extension findings, this could pave the way to further testing NMN’s potential in humans. In that regard, figuring out whether NMN boosts the number of healthy, disease-free years people live (healthspan) and lifespan would become paramount.

Such a scenario would come in the face of the FDA’s ban on selling NMN as a supplement. Along those lines, it is possible that positive effects on healthy mouse lifespan from NMN could also help sway the FDA to reverse its ban.