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.

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.

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.