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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aging / drug effects*
  • Aging / genetics
  • Aging / physiology*
  • Animals
  • Bone Density / drug effects
  • Cell Respiration / drug effects
  • Darkness
  • Drinking / drug effects
  • Eating / drug effects
  • Energy Metabolism / drug effects
  • Food
  • Gene Expression Regulation / drug effects
  • Insulin / pharmacology
  • Lipids / blood
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Myeloid Cells / drug effects
  • Myeloid Cells / metabolism
  • NAD / metabolism
  • Nicotinamide Mononucleotide / administration & dosage*
  • Nicotinamide Mononucleotide / blood
  • Nicotinamide Mononucleotide / pharmacology*
  • Physical Conditioning, Animal
  • Time Factors
  • Weight Gain / drug effects

Substances

  • Insulin
  • Lipids
  • NAD
  • Nicotinamide Mononucleotide