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

Cell Metab. 2018 Mar 6;27(3):513-528. doi: 10.1016/j.cmet.2017.11.002. Epub 2017 Dec 14.

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.

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.

Publication types

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

MeSH terms

  • Aging / metabolism*
  • Animals
  • Humans
  • NAD / metabolism*
  • Niacinamide / analogs & derivatives*
  • Niacinamide / metabolism
  • Nicotinamide Mononucleotide / metabolism*

Substances

  • nicotinamide-beta-riboside
  • NAD
  • Nicotinamide Mononucleotide
  • Niacinamide