Highlights: 

  • Increasing cellular NAD+ with NMN restores the structure of the intestinal wall in old mice, suggesting improved nutrient absorption. 
  • NMN increases the activation of genes associated with gut barrier integrity, providing a means to restore the function of a leaky gut.  
  • Intestinal wall fortification is achieved by boosting antioxidant defenses and reducing inflammation via NMN. 

Our intestines not only absorb the nutrients necessary to sustain life but also act as a protective barrier from the outside world. When this barrier is disrupted, harmful molecules like pathogens can sneak into our bloodstream and wreak havoc on the rest of our organs. Research suggests that this barrier becomes compromised with aging. However, a new study published in Food & Function shows that nicotinamide mononucleotide (NMN) can help. 

Researchers from the Jiangxi Academy of Sciences in China report that NMN, a molecule capable of boosting nicotinamide adenine dinucleotide (NAD+), protects against age-related intestinal dysfunction. Ru and colleagues show that NMN boosts NAD+ and restores intestinal wall structure in older mice. They also show that NMN increases genes associated with gut barrier integrity. Additionally, the results suggest that NMN works by reducing inflammation and boosting natural (endogenous) antioxidants.

NMN Rebuilds and Fortifies the Intestinal Lining of Old Mice

Our intestinal lining is far from smooth, consisting of projections called villi. These tiny gut wall folds increase the surface area of our intestine to the size of a tennis court, maximizing nutrient absorption. Ru and colleagues found that putting NMN in the drinking water of old mice increases the height of their villi, suggesting improved nutrient absorption. Furthermore, NMN was shown to increase NAD+ levels in the same area of the small intestine called the jejunum. 

(Ru et al., 2022 | Food & Function) Boosting NAD+ with NMN Restores Intestinal Wall Structure in Old Mice. In a portion of the small intestine called the jejunum, oral NMN treatment increases villus height (left) and raises NAD+ levels (right).

The cells that make up our intestinal lining have gaps between them that, if too wide, can allow large harmful molecules into our bloodstream. These gaps can be narrowed by specific proteins at choke points called tight junctions (see the main image). Ru and colleagues found that NMN increases the activation of the genes associated with these proteins in older mice, suggesting that NMN reduces gut wall permeability to harmful molecules.

(Ru et al., 2022 | Food & Function) NMN Elevates Gut Barrier Genes in Old Mice. NMN increases the activation of genes associated with gut barrier integrity (Occludin and Claudin-1). 

To determine how NMN could be reversing intestinal aging, Ru and colleagues measured genes associated with natural antioxidants and inflammation. They found that NMN increases the activation of genes associated with antioxidants (such as SOD2 and Nrf2) and decreases genes associated with inflammation. Antioxidants are capable of quelling harmful free radicals called reactive oxygen species (ROS), which contribute largely to inflammation and the organ and tissue dysfunction associated with aging. 

Furthermore, NMN increases the activation of sirtuins (Sirt3 and Sirt6) — enzymes that use NAD+ as fuel, associated with improving antioxidant capacity and reducing inflammation. These findings suggest that NMN reverses intestinal aging by boosting antioxidants and mitigating inflammation through sirtuin activation.

Can NMN Prevent Multiple Diseases?

In addition to this study, NMN has been shown to protect the intestinal tract, rejuvenate intestinal stem cells, and rescue colon degeneration in older rodents. Another NAD+ precursor, nicotinamide riboside (NR) has been shown to improve intestinal lining function and also rejuvenate intestinal stem cells. These studies suggest that boosting NAD+, a molecule that declines with aging and is thought to underlie age-related conditions like neurodegeneration, heart disease, and obesity, may also underlie intestinal aging. Since leaky gut has been associated with liver disease and Alzheimer’s disease, it’s possible that boosting NAD+ with NMN can contribute to preventing or mitigating these diseases and other diseases by reversing intestinal aging as well.