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.