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Cell Metab. 2016 Dec 13;24(6):795-806. doi: 10.1016/j.cmet.2016.09.013. Epub 2016 Oct 27.

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

Author information

1
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Oriental Yeast Company, Tokyo 174-0051, Japan.
3
Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
5
School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland BT7 1NN, UK.
6
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO 63110, USA.
7
Division of Geriatrics and Nutritional Science, Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: jyoshino@wustl.edu.
8
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: imaishin@wustl.edu.

Abstract

NAD+ availability decreases with age and in certain disease conditions. Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been shown to enhance NAD+ biosynthesis and ameliorate various pathologies in mouse disease models. In this study, we conducted a 12-month-long NMN administration to regular chow-fed wild-type C57BL/6N mice during their normal aging. Orally administered NMN was quickly utilized to synthesize NAD+ in tissues. Remarkably, NMN effectively mitigates age-associated physiological decline in mice. Without any obvious toxicity or deleterious effects, NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile, and ameliorated eye function and other pathophysiologies. Consistent with these phenotypes, NMN prevented age-associated gene expression changes in key metabolic organs and enhanced mitochondrial oxidative metabolism and mitonuclear protein imbalance in skeletal muscle. These effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective anti-aging interventions in humans.

KEYWORDS:

NAD(+); NAD(+) precursor; NMN; aging; anti-aging; energy metabolism; eye function; glucose metabolism; insulin sensitivity; mitochondria; nicotinamide mononucleotide

PMID:
28068222
PMCID:
PMC5668137
DOI:
10.1016/j.cmet.2016.09.013
[Indexed for MEDLINE]
Free PMC Article

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