NAD+ Metabolism encompasses the intricate biochemical pathways responsible for the synthesis, utilization, and recycling of Nicotinamide Adenine Dinucleotide (NAD+) and its related forms within the cell. NAD+ is an essential coenzyme required for hundreds of redox reactions and is a critical substrate for NAD+-consuming enzymes, including sirtuins and PARPs. Declining cellular NAD+ levels are a recognized hallmark of aging, making its metabolic regulation a key target for longevity and hormonal optimization strategies. Maintaining high NAD+ levels is vital for cellular energy production.
Origin
The discovery of NAD+ dates back to 1906, with its role in cellular respiration elucidated over the subsequent decades. The concept of “NAD+ metabolism” as a longevity target gained significant attention in the early 21st century with the discovery of sirtuins and the recognition of age-related NAD+ depletion. This established NAD+ as a central node linking energy status, DNA repair, and the overall aging process.
Mechanism
NAD+ is synthesized primarily through the salvage pathway, utilizing precursors like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) to rapidly replenish cellular pools. The coenzyme functions as an electron acceptor in catabolic pathways, such as glycolysis and the Krebs cycle, and as a substrate for signaling enzymes. Its consumption by sirtuins, which regulate gene expression and stress resistance, links NAD+ availability directly to genomic stability and endocrine health.
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