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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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).
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.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Peer review information Primary handling editor: Christoph Schmitt.
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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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