Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice
Mills KF, Yoshida S, Stein LR, et al.
Key finding
12 months of oral NMN at 100-300 mg/kg/day prevents multi-system age-associated physiological decline in mice without adverse effects. Source: Mills KF, Yoshida S, Stein LR, et al. Cell Metabolism, 2016.
Summary
12-month chronic-administration study of oral NMN in wild-type C57BL/6N mice, from the Imai laboratory. Animals received 100 or 300 mg/kg/day NMN in drinking water starting at 5 months of age and continuing through 17 months. NMN supplementation significantly mitigated age-associated declines in insulin sensitivity, plasma lipids, body composition (retained lean mass and reduced fat mass), energy expenditure, physical activity, and mitochondrial function in skeletal muscle. Eye function and bone density were also preserved. Importantly, long-term NMN raised tissue NAD+ without adverse effects on liver or kidney function across a full year of continuous exposure, addressing safety concerns that had limited chronic rodent studies up to that point. The study is the most frequently cited preclinical justification for human NMN trials, both in magnitude of tissue effect and in demonstrating durable multi-system benefit over near-lifespan timescales. Dose-response was evident, with 300 mg/kg/day producing larger effects than 100 mg/kg/day.
For background on the compound studied here, see our NMN precursor reference.
Frequently asked questions
- What did Mills et al. (2016) find about NMN?
- 12 months of oral NMN at 100-300 mg/kg/day prevents multi-system age-associated physiological decline in mice without adverse effects. Source: Mills KF, Yoshida S, Stein LR, et al. "Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice." Cell Metabolism, 2016.
- What kind of study is Mills 2016?
- It is a mechanism study on NMN published in Cell Metabolism in 2016. 12-month chronic-administration study of oral NMN in wild-type C57BL/6N mice, from the Imai laboratory. Animals received 100 or 300 mg/kg/day NMN in drinking water starting at 5 months of age and continuing through 17 months. NMN supplementation significantly mitigated age-associated declines in insulin sensitivity, plasma lipids, body composition (retained lean mass and reduced fat mass), energy expenditure, physical activity, and mitochondrial function in skeletal muscle. Eye function and bone density were also preserved. Importantly, long-term NMN raised tissue NAD+ without adverse effects on liver or kidney function across a full year of continuous exposure, addressing safety concerns that had limited chronic rodent studies up to that point. The study is the most frequently cited preclinical justification for human NMN trials, both in magnitude of tissue effect and in demonstrating durable multi-system benefit over near-lifespan timescales. Dose-response was evident, with 300 mg/kg/day producing larger effects than 100 mg/kg/day.
- Where can I read the full Mills 2016 paper?
- The primary source is available on PubMed (PMID 28068222) and via DOI 10.1016/j.cmet.2016.09.013.
Access the full paper
Related research
Nature Metabolism · 2019
Slc12a8 is a nicotinamide mononucleotide transporter
Oral NMN reaches tissues intact via a dedicated intestinal transporter.
Science · 2021
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
NMN improved skeletal muscle insulin sensitivity and gene expression in postmenopausal women.
Cell · 2013
Declining NAD induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging
Short-term NMN restores aged-mouse muscle NAD+ and reverses pseudohypoxic mitochondrial dysfunction, implicating NAD+ decline as a causal aging driver.