NAD⁺ metabolism: a therapeutic target for age-related metabolic disease.
- Mouchiroud L Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
- Houtkooper RH Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands.
- Auwerx J Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
- 2013-06-08
Published in:
- Critical reviews in biochemistry and molecular biology. - 2013
English
Nicotinamide adenine dinucleotide (NAD) is a central metabolic cofactor by virtue of its redox capacity, and as such regulates a wealth of metabolic transformations. However, the identification of the longevity protein silent regulator 2 (Sir2), the founding member of the sirtuin protein family, as being NAD⁺-dependent reignited interest in this metabolite. The sirtuins (SIRT1-7 in mammals) utilize NAD⁺ to deacetylate proteins in different subcellular compartments with a variety of functions, but with a strong convergence on optimizing mitochondrial function. Since cellular NAD⁺ levels are limiting for sirtuin activity, boosting its levels is a powerful means to activate sirtuins as a potential therapy for mitochondrial, often age-related, diseases. Indeed, supplying excess precursors, or blocking its utilization by poly(ADP-ribose) polymerase (PARP) enzymes or CD38/CD157, boosts NAD⁺ levels, activates sirtuins and promotes healthy aging. Here, we discuss the current state of knowledge of NAD⁺ metabolism, primarily in relation to sirtuin function. We highlight how NAD⁺ levels change in diverse physiological conditions, and how this can be employed as a pharmacological strategy.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.3109/10409238.2013.789479
- PMID 23742622
- Persistent URL
- https://sonar.ch/global/documents/99433
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