The Central Role of the NAD+ Molecule in the Development of Aging and the Prevention of Chronic Age-Related Diseases: Strategies for NAD+ Modulation

Int J Mol Sci. 2023 Feb 3;24(3):2959. doi: 10.3390/ijms24032959.

Abstract

The molecule NAD+ is a coenzyme for enzymes catalyzing cellular redox reactions in several metabolic pathways, encompassing glycolysis, TCA cycle, and oxidative phosphorylation, and is a substrate for NAD+-dependent enzymes. In addition to a hydride and electron transfer in redox reactions, NAD+ is a substrate for sirtuins and poly(adenosine diphosphate-ribose) polymerases and even moderate decreases in its cellular concentrations modify signaling of NAD+-consuming enzymes. Age-related reduction in cellular NAD+ concentrations results in metabolic and aging-associated disorders, while the consequences of increased NAD+ production or decreased degradation seem beneficial. This article reviews the NAD+ molecule in the development of aging and the prevention of chronic age-related diseases and discusses the strategies of NAD+ modulation for healthy aging and longevity.

Keywords: NAD+ levels; NAD+ precursors; PARP; sirtuin.

Publication types

  • Review

MeSH terms

  • Electron Transport
  • NAD* / metabolism
  • Oxidation-Reduction
  • Poly(ADP-ribose) Polymerases / metabolism
  • Sirtuins* / metabolism

Substances

  • NAD
  • Poly(ADP-ribose) Polymerases
  • Sirtuins

Grants and funding

This research was funded by Slovenian Research Agency, grant numbers P3-0388 and P3-0019.