Role of NAD(+) in regulating cellular and metabolic signaling pathways

BACKGROUND: Nicotinamide adenine dinucleotide (NAD(+)), a critical coenzyme present in every living cell, is involved in a myriad of metabolic processes associated with cellular bioenergetics. For this reason, NAD(+) is often studied in the context of aging, cancer, and neurodegenerative and metabolic disorders. SCOPE OF REVIEW: Cellular NAD(+) depletion is associated with compromised adaptive cellular stress responses, impaired neuronal plasticity, impaired DNA repair, and cellular senescence. Increasing evidence has shown the efficacy of boosting NAD(+) levels using NAD(+) precursors in various diseases. This review provides a comprehensive understanding into the role of NAD(+) in aging and other pathologies and discusses potential therapeutic targets. MAJOR CONCLUSIONS: An alteration in the NAD(+)/NADH ratio or the NAD(+) pool size can lead to derailment of the biological system and contribute to various neurodegenerative disorders, aging, and tumorigenesis. Due to the varied distribution of NAD(+)/NADH in different locations within cells, the direct role of impaired NAD(+)-dependent processes in humans remains unestablished. In this regard, longitudinal studies are needed to quantify NAD(+) and its related metabolites. Future research should focus on measuring the fluxes through pathways associated with NAD(+) synthesis and degradation.