Taking NMN by under-the-skin injections or oral consumption improves immune cells that attack cancer and virally infected cells in mice.(Alpha Tauri 3D Graphics | Shutterstock)
· NMN increases natural killer cell capabilities to destroy cancer cells (cytotoxicity) without increasing immune cell numbers.
· The study supports that taking NMN may be a way to rejuvenate natural killer immune cell activation to preserve tissue health during aging.
As the average human lifespan increases, people are experiencing poor health and age-related diseases longer, incurring major financial and societal costs. One substantial contributing factor to age-related diseases and their progression is degraded immune function. Specifically, NK cells that terminate cancer and virally infected cells become less effective. At present, no remedy exists to restore the function of NK cells during aging. So, compounds that stimulate NK cell activation may prevent age-related ailments or slow their advancement.
Okumura and colleagues from Juntendo University in Japan treated mice with nicotinamide mononucleotide (NMN) to restore NK cell cytotoxicity — the ability to destroy malfunctioning cells. Published in Biomedical Research, NK cell stimulation in mice occurred when NMN was injected (313, 625, or 1250 mg/kg) or orally administered (625 mg/kg) for four days. Notably, the boosted NK cell cytotoxicity didn’t come from their enhanced proliferation or higher NK cell numbers but rather improved NK cell abilities to destroy cancer cells. These findings support that NMN supplementation may boost NK cell immunity and overall tissue health by curtailing the accumulation of precancerous and viral-infected cells as people age.
Many aspects of immunity decline with age, and NK immune cell function is no exception to this phenomenon. The age-related deterioration of immune function with age is linked to levels of an essential molecule called nicotinamide adenine dinucleotide (NAD+), which also declines with age. However, boosting NAD+ levels has been shown to improve immune function in mice. For example, studies have shown that increasing NAD+ levels by inhibiting an NAD+-consuming enzyme improves immunity to attenuate tumors in mice.
The NAD+ precursor NMN helps with age-related disorders like insulin insensitivity and metabolic impairments like obesity in aged mice. Also, since boosting NAD+ levels have been shown to work against tumors in mice, it may also potentially enhance anti-tumor NK cell activity. Figuring out whether NMN has these immunity-restoring effects in NK cells is critical for determining if it is the compound we’ve been looking for to restore their cytotoxicity.
To analyze NMN’s influence on NK cells, Takeda and Okumura injected mice at various ages with NMN and evaluated the activation and cytotoxicity of NK cells. The research duo injected varying doses of 1250, 625, 313, or 125 mg/kg/day of NMN for four days into 36-week old mice and then harvested NK cells from the liver and spleen. These NK cells were then put into a dish with cancer cells at different ratios and were analyzed for cytotoxicity based on the percentage of destroyed cancer cells. These findings indicate that injecting 313 mg/kg or more of NMN enhances aged NK cell capabilities to destroy dysfunctional cells in mice.
Using the same cytotoxicity measurement method, the research team then sought to determine whether similar benefits come from administering NMN orally. In the 32-week-old mice Takeda and Okumura used for their analysis, 625 mg/kg of orally-supplemented NMN significantly enhanced NK cell cytotoxicity. Neither injecting or orally dosing NMN increased the NK cell numbers. This result strongly supports that NMN supplementation improves overall NK cell cytotoxicity in mice, because NK cells show improved, potent cancer cell-destroying abilities without becoming more abundant.
“We have herein demonstrated that intraperitoneal or oral administration of NMN, a key NAD+ intermediate in mammals, augments the cytotoxicity of NK cells,” said Okumura and colleagues in their publication.
Studies continue to show the translatability of NMN’s health benefits from mice to humans in conditions like reduced insulin sensitivity, running endurance, and aged muscle function. So, although how and whether these results apply to humans remain up in the air, the study offers hope for the tantalizing prospect that NMN improves aged human immunity through improved NK cell cytotoxicity.
Some study limitations include that NMN boosts NK cell cytotoxicity optimally at different ratios of NK cells to cancer cells, but the significance of this finding wasn’t explored. For example, the optimal proportion of NK cells to cancer cells with oral dosages is 10 to 20 in the liver but 200 in the spleen. The precise meaning of this finding remains uncertain.
Another limitation is that the cytotoxicity analyses were done in laboratory dishes, which don’t always translate to live tissue. Future experiments can utilize cytotoxicity measurements in live animal tissues to further support that NMN boosts NK cell cytotoxicity.