NAD+

Research · NAD+

Overview

NAD+ (nicotinamide adenine dinucleotide, oxidized form) is a ubiquitous dinucleotide cofactor composed of nicotinamide mononucleotide and adenosine monophosphate joined by a pyrophosphate bridge. It functions as a central electron carrier in cellular energy metabolism and as a consumed substrate for several enzyme families. It is a standard reagent in enzymology and metabolic research, and tissue NAD+ levels are widely measured in studies of cellular aging. It is supplied as a reagent for dehydrogenase assays and for studies of sirtuin and PARP enzymology.

Mechanism of action

As a hydride acceptor, NAD+ is reduced to NADH in glycolysis, the tricarboxylic acid pathway, and fatty acid oxidation, with NADH reoxidized by mitochondrial complex I to drive oxidative phosphorylation. Separately, NAD+ is cleaved as a substrate by sirtuin deacylases, poly(ADP-ribose) polymerases involved in DNA repair, and the CD38/CD157 glycohydrolases, releasing nicotinamide. Cellular pools are maintained primarily through the salvage pathway, in which nicotinamide phosphoribosyltransferase (NAMPT) is rate-limiting, with additional de novo synthesis from tryptophan and the Preiss-Handler pathway from nicotinic acid. Compartmentalized pools in the nucleus, cytosol, and mitochondria are maintained semi-independently.

Key research findings

1. 01

   Rodent and human tissue studies have characterized age-associated declines in NAD+ levels across multiple organs.

2. 02

   Mouse studies have linked tissue NAD+ decline to increased CD38 expression, including on inflammatory macrophages activated by senescent cells.

3. 03

   Preclinical models have characterized the effects of supplying precursors such as nicotinamide riboside and nicotinamide mononucleotide on tissue NAD+ content and sirtuin-dependent signaling.

4. 04

   Early-phase clinical studies have characterized the pharmacokinetics of NAD+ precursors and their effects on blood NAD+ metabolite levels in healthy participants.

Published references

• NAD(+) metabolism and its roles in cellular processes during ageing

  Covarrubias AJ et al. — Nat Rev Mol Cell Biol, 2021 · PMID: 33353981

• NAD⁺ in aging, metabolism, and neurodegeneration

  Verdin E — Science, 2015 · PMID: 26785480

The information above is derived from published preclinical and clinical research. It is provided for educational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations.