NAD+ Homeostasis refers to the maintenance of a stable and optimal ratio of the oxidized form of nicotinamide adenine dinucleotide (NAD+) to its reduced form (NADH) within the cell. NAD+ is an essential coenzyme central to energy metabolism, DNA repair, and gene expression regulation, acting as a substrate for sirtuins and PARPs. Maintaining this balance is critical for cellular resilience, metabolic flexibility, and healthy aging, all of which impact hormonal signaling.
Origin
This concept is derived from foundational biochemistry and is a central focus of longevity research, particularly mitochondrial biology. The term ‘homeostasis’ emphasizes the body’s need to actively regulate the synthesis, consumption, and recycling of this vital molecule to sustain life processes. Decline in NAD+ levels is a recognized hallmark of aging and metabolic dysfunction.
Mechanism
NAD+ acts as an electron acceptor in the Krebs cycle and oxidative phosphorylation, driving ATP production in the mitochondria. It is also consumed by NAD+-dependent enzymes, such as the sirtuins, which regulate gene silencing and stress response pathways. Homeostasis is maintained by the salvage pathway, which recycles NAD+ precursors, and is clinically supported by interventions aimed at boosting the availability of these precursors to sustain the NAD+ pool.
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