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.
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.
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