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

*Corresponding author for this work

Research output: Contribution to journalArticle

184 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)795-806
Number of pages12
JournalCell metabolism
Volume24
Issue number6
Early online date27 Oct 2016
DOIs
Publication statusPublished - 13 Dec 2016

Keywords

  • aging
  • anti-aging
  • energy metabolism
  • eye function
  • glucose metabolism
  • insulin sensitivity
  • mitochondria
  • NAD
  • NAD precursor
  • nicotinamide mononucleotide
  • NMN

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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