NAD + Intermediates: The Biology and Therapeutic Potential of NMN and NR

Jun Yoshino, Joseph A. Baur, Shin ichiro Imai

Research output: Contribution to journalReview articlepeer-review

302 Scopus citations

Abstract

Research on the biology of NAD + has been gaining momentum, providing many critical insights into the pathogenesis of age-associated functional decline and diseases. In particular, two key NAD + intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years. Supplementing these NAD + intermediates has shown preventive and therapeutic effects, ameliorating age-associated pathophysiologies and disease conditions. Although the pharmacokinetics and metabolic fates of NMN and NR are still under intensive investigation, these NAD + intermediates can exhibit distinct behavior, and their fates appear to depend on the tissue distribution and expression levels of NAD + biosynthetic enzymes, nucleotidases, and presumptive transporters for each. A comprehensive concept that connects NAD + metabolism to the control of aging and longevity in mammals has been proposed, and the stage is now set to test whether these exciting preclinical results can be translated to improve human health. NAD + is increasingly being recognized to play an important role in the pathogenesis of age-associated functional decline and diseases. Two key NAD + intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been instrumental in driving recent discoveries. We discuss key findings and future therapeutic and translational potential for these molecules.

Original languageEnglish
Pages (from-to)513-528
Number of pages16
JournalCell metabolism
Volume27
Issue number3
DOIs
StatePublished - Mar 6 2018

Keywords

  • NAD
  • NAMPT
  • NMN
  • NMN adenylyltransferases
  • NMNATs
  • NR
  • NR kinases
  • NRKs
  • PARPs
  • aging
  • metabolism
  • nicotinamide adenine dinucleotide
  • nicotinamide mononucleotide
  • nicotinamide phosphoribosyltransferase
  • nicotinamide riboside
  • poly-ADP-ribose polymerases
  • sirtuins

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