NAD+ homeostasis in health and disease

Abstract

The conceptual evolution of nicotinamide adenine dinucleotide (NAD+) from being seen as a simple metabolic cofactor to a pivotal cosubstrate for proteins regulating metabolism and longevity, including the sirtuin family of protein deacylases, has led to a new wave of scientific interest in NAD+. NAD+ levels decline during ageing, and alterations in NAD+ homeostasis can be found in virtually all age-related diseases, including neurodegeneration, diabetes and cancer. In preclinical settings, various strategies to increase NAD+ levels have shown beneficial effects, thus starting a competitive race to discover marketable NAD+ boosters to improve healthspan and lifespan. Here, we review the basics of NAD+ biochemistry and metabolism, and its roles in health and disease, and we discuss current challenges and the future translational potential of NAD+ research.

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Fig. 1: Main biochemical reactions requiring NAD+/NADH as a coenzyme.
Fig. 2: The main NAD+-consuming enzymes.
Fig. 3: NAD+-biosynthesis pathways.
Fig. 4: Disease conditions associated with altered NAD+ homeostasis.

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Acknowledgements

This work was supported by grants from the EPFL, the European Research Council (ERC-AdG-787702), the Swiss National Science Foundation (SNSF 310030B-160318 and SNF NAD 31003A_179435), the Fondation Suisse de Recherche sur les Maladies Musculaires (FSRMM), the AgingX program of the Swiss Initiative for Systems Biology (RTD 2013/153) and the NIH (R01AG043930).

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E.K., M.R., D.H. and J.A. wrote the manuscript.

Correspondence to Johan Auwerx.

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Competing interests

J.A. is a consultant to Mitobridge-Astellas, MetroBiotech and TES pharma, companies that develop NAD+-boosting therapies. E.K., M.R. and D.H. declare no conflicts of interest.

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Katsyuba, E., Romani, M., Hofer, D. et al. NAD+ homeostasis in health and disease. Nat Metab 2, 9–31 (2020). https://doi.org/10.1038/s42255-019-0161-5

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