Nicotinamide Mononucleotide Reduces Age-Related Health Decline in Mice

As cells age, their ability to produce and efficiently utilize energy begins to decline, potentially resulting in deterioration in health. While the reason behind this age-related energy decline is unknown, researchers at Washington University School of Medicine in St. Louis have shown that giving a nicotinamide mononucleotide (NMN) supplement to healthy mice could be compensatory for the decline in cellular energy production.

These researchers found that NMN was able to reduce multiple signs of aging, including weight gain, diminished physical activity and loss of insulin sensitivity. The research was published in the journal, Cell Metabolism.

“We have shown a way to slow the physiologic decline that we see in aging mice,” said Dr. Shin-ichiro Imai, a professor of developmental biology and of medicine at the Washington University School of Medicine. “This means older mice have metabolism and energy levels resembling that of younger mice. Since human cells rely on this same energy production process, we are hopeful this will translate into a method to help people remain healthier as they age.”

Based on the promising results Imai and his team identified in preclinical mouse studies, the compound is now being tested in humans. A Phase I clinical trial testing the safety of NMN in human participants was started earlier this year at Keio University School of Medicine in Tokyo.

Levels of a key component of cellular energy production – known as nicotinamide adenine dinucleotide (NAD) – decline in many tissue types as cells age. Previous work conducted by Imai and his colleagues has shown that directly supplementing mice with NAD was not an effective method to boost cellular energy levels.

Instead, the researchers decided to supplement mice with NMN, which happens to be a key component of the NAD coenzyme generation pathway. As a derivative of vitamin B3, NMN is found in multiple foods, including cabbage, broccoli and cucumber.

By dissolving the supplement in water, the researchers were able to rapidly deliver NMN to the bloodstream of mice in fewer than three minutes. Imai and his team also found that the NMN was quickly converted to NAD in multiple tissue types throughout the mice.

“We wanted to make sure that when we give NMN through drinking water, it actually goes into the blood circulation and into tissues,” said Imai. “Our data show that NMN absorption happens very rapidly.”

To determine how NMN supplementation affects the long-term health of the mice, the researchers split the animals into three test groups receiving a high dose of NMN, low dose of NMN or no dose of NMN as a control. Animals that received either dose of NMN saw benefits to multiple tissues, including liver function, bone density, insulin sensitivity and immune function. Interestingly, these benefits were only observed in older mice.

“When we give NMN to the young mice, they do not become healthier young mice,” said Dr. Jun Yoshino, an assistant professor of medicine at Washington University School of Medicine. “NMN supplementation has no effect in the young mice because they are still making plenty of their own NMN. We suspect that the increase in inflammation that happens with aging reduces the body’s ability to make NMN and, by extension, NAD.”