By the year 2050, researchers project that the global population over the age of 60 will be as high as 1.2 billion, constituting what aging scientists call the “silver tsunami.” And as people get older, the repeated DNA sequences at the ends of our chromosomes (telomeres) shorten. The erosion of telomeres leads to disorders associated with aging like metabolic disease and heart complications.
Along these lines, inflammation from aging disrupts the balance between helpful and harmful gut bacteria, leading to inflammation that precedes age-related diseases (inflammaging). Previous studies have indicated that the nicotinamide adenine dinucleotide (NAD+) precursor, NMN, lengthens telomeres and restores healthy gut microbes. Whether NMN provides these benefits for people has not yet been examined thoroughly with clinical trials.
Wu and colleagues from the Tianjin Institute of Industrial Biotechnology have shown in a recent publication from a clinical trial that administering 500 mg/L of NMN in drinking water to 16-month-old pre-aging mice (equivalent to 45-60 year-old people) for 40 days reduces gut microbiome diversity and increases telomere length. The China-based team also found that oral NMN supplementation doubles telomere length over 90 days in human blood cells called peripheral blood mononuclear cells (PBMCs). Given these findings, it’s possible that increasing telomere length may inhibit the onset of age-related diseases to enhance healthspan and also potentially increase lifespan.
NMN Boosts Metabolism in Mice
To establish the benefits of NMN given to mice, Wu and colleagues measured thermogenesis, the output of body heat, which correlates to increased cell energy production. Thermogenesis is a biomarker, a biological indicator, of metabolism — the generation of energy through cellular processes that produce the energy packet molecule adenosine triphosphate (ATP). The assessment of metabolism through body heat showed that administering NMN over a 40-week time course increases thermogenesis by about 10%, confirming that the compound improves metabolic function.
(Wu et al., 2021 | Frontiers in Nutrition) Short-term NMN supplementation in middle-aged mice significantly increases thermogenesis, the metabolic production of body heat. The left figure is a heat map showing body heat production of a healthy mouse on the left and an NMN-fed mouse with amplified thermogenesis on the right. The bar graph on the right illustrates that the heat yield after 40 weeks of NMN administration increased by about 10%.
NMN Alters Intestinal Bacteria Diversity
Wu and colleagues next measured fecal bacteria composition in mice and found that NMN promotes a healthy gut by improving bacterial composition. Intestinal bacteria health is a biomarker of overall physiological well-being. The Tianjin researchers observed that short-term NMN administration reduced the diversity of bacterial species in the intestine. Notably, several species of healthy gut-associated bacteria species increased in abundance, like Mucispirillum, Colidextribacter, and Candidatus_Saccharimonas. On the other hand, bacteria often found in patients with age-related diseases like Staphylococcus, Corynebacterium, and Paenalcaligenes diminished in prevalence.
Oral Usage of NMN Drives Telomere Extension
Wu and colleagues then measured the length of telomeres in mice and humans. The team found that administering NMN for short time periods increases telomere lengths 20-25% in mice. The researchers also found that taking NMN for short periods of time (90 days) almost doubles the length of telomeres in humans, indicating potentially breakthrough health benefits and lifespan extension effects.
(Wu et al., 2021 | Frontiers in Nutrition) Administering NMN to mice and people substantially extends telomere length in immune cells. The left figure shows telomere length increased by about 20% in peripheral blood mononuclear cells (PBMCs). The figure on the right illustrates that telomere lengths linearly increase such that by 90 days of orally taking NMN, telomere length almost doubled.
The evidence gathered from this research study provides insight that NMN improves gut microbial composition in mice and telomere length in mice along with people, and these effects may drastically improve healthspan. Whether or not NMN promotes a longer lifespan, the study indicates that it might help people extend the number of years they live in health and wellbeing.
Limitations to the study include that long-term NMN supplementation was not examined. The way that the body metabolizes NMN, especially in higher dosages, must be checked, also. Furthermore, what effects a lower diversity of gut flora may have during aging will require further investigation. In essence, a concern that researchers should confront soon is “how much NMN is too much?” The answer to this question will likely depend on the medical history and available clinical guidance for those who decide to use this compound.
Niu KM, Bao T, Gao L, Ru M, Li Y, Jiang L, Ye C, Wang S, Wu X. The Impacts of Short-Term NMN Supplementation on Serum Metabolism, Fecal Microbiota, and Telomere Length in Pre-Aging Phase. Front Nutr. 2021 Nov 29;8:756243. doi: 10.3389/fnut.2021.756243. PMID: 34912838; PMCID: PMC8667784.