Role of NAD + in regulating cellular and metabolic signaling pathways.

Abstract 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, 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. Growing evidence has shown the efficacy of boosting NAD+ levels by using NAD+ precursors in various diseases. This review aims to provide 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 the cell, 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.