The Role of NAD⁺ Metabolism in Cellular Aging and Longevity

Nicotinamide adenine dinucleotide (NAD⁺) is a crucial coenzyme involved in numerous cellular processes, including energy metabolism, DNA repair, and cell signaling. Its levels decline with age, and this decline has been implicated in the aging process and age-related diseases. NAD⁺ metabolism is tightly regulated by a variety of enzymes, including sirtuins, poly(ADP-ribose) polymerases (PARPs), and NAD⁺-dependent deacetylases, all of which contribute to cellular homeostasis and longevity. This review provides an in-depth analysis of the role of NAD⁺ metabolism in cellular aging, focusing on its impact on mitochondrial function, oxidative stress, and cellular repair mechanisms. We explore how NAD⁺ is involved in key biochemical pathways, such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation, and how its depletion leads to a decline in cellular energy production and increased susceptibility to cellular damage. We also discuss the role of NAD⁺ in maintaining genomic stability through DNA repair pathways, particularly those mediated by PARPs and sirtuins, and how this impacts aging and longevity. Furthermore, we examine the potential therapeutic strategies for restoring NAD⁺ levels, including the use of NAD⁺ precursors (e.g., nicotinamide riboside and nicotinamide mononucleotide) and pharmacological interventions targeting the enzymes involved in NAD⁺ biosynthesis and degradation. The review also addresses the emerging field of NAD⁺ metabolism as a therapeutic target for age-related diseases, such as neurodegenerative disorders, cardiovascular diseases, and metabolic syndrome. Ultimately, understanding the role of NAD⁺ in cellular aging offers exciting opportunities for developing interventions that could extend lifespan and improve healthspan.