Tier 3 — preclinical

Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice

Kathryn F Mills, Shohei Yoshida, Liana R Stein, Alessia Grozio, Shunsuke Kubota, Yo Sasaki, Philip Redpath, Marie E Migaud, Rajendra S Apte, Koji Uchida, Jun Yoshino, Shin-Ichiro Imai
Cell Metabolism 2016 24(6):795-806

Bibliography

PubMed
PMID 28068222
PubMed Central
PMC5668137
DOI
10.1016/j.cmet.2016.09.013
Funding
Conducted under a sponsored research agreement between Washington University and Oriental Yeast Co.; additional support included U.K. Research Councils/BBSRC and institutional research-center resources.
Competing interests
Rajendra S. Apte was a co-founder of Metro Midwest Biotech; Marie E. Migaud served as a consultant for ChromaDex. Oriental Yeast Co. supported the sponsored research and produced NMN used in the study.

Study snapshot

Design12-month controlled oral NMN intervention in naturally aging wild-type C57BL/6N mice, plus pharmacokinetic tracing, tissue analyses and food-source NMN quantification.
ModelRegular chow-fed wild-type C57BL/6N mice undergoing normal aging.
SampleMouse cohorts varied by endpoint; longitudinal treatment groups generally included approximately 9–15 animals per group.
InterventionNMN in drinking water at 100 or 300 mg/kg/day for 12 months; additional acute pharmacokinetic experiments used oral NMN.
Duration12 months for the chronic aging intervention.
EndpointsTissue NAD+; Body weight; Energy expenditure; Physical activity; Insulin sensitivity; Plasma lipids; Eye function; Bone density; Immune-cell composition; Tissue gene expression; Mitochondrial function; Natural-food NMN content

What the study showed, in plain terms

This landmark mouse study gave NMN continuously for 12 months during normal aging and found broad improvements across several physiological and metabolic measures, without obvious toxicity in the treated mice.

It is also one of the commonly cited primary sources for naturally occurring NMN in foods. The measured concentrations were fractions to low single-digit milligrams per 100 grams of food — far below the hundreds of milligrams used in modern human supplementation trials.

The study is foundational preclinical evidence, but its anti-aging outcomes occurred in mice and should not be presented as proof that NMN slows human aging.

Key findings

  • Long-term oral NMN increased tissue NAD+ availability and was well tolerated in the mouse model.
  • NMN suppressed age-associated weight gain and improved energy metabolism, physical activity, insulin sensitivity and several other age-related measures in mice.
  • Skeletal-muscle mitochondrial oxidative metabolism and tissue gene-expression patterns were favorably altered.
  • The study detected NMN in foods including edamame, broccoli, cucumber, cabbage, avocado, tomato, mushroom, raw beef and shrimp.
  • Food concentrations were orders of magnitude below common human supplemental doses.

What this study can and cannot tell us

The central efficacy findings are from mice, not people. Mouse doses and physiology cannot be translated directly into claims of human lifespan or healthspan benefit.

The food measurements establish that NMN occurs naturally but do not show that eating these foods raises human NAD+ to the same degree as supplemental doses.

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Editorial review

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology