NAD+ bioavailability refers to the fraction of exogenously administered or endogenously synthesized Nicotinamide Adenine Dinucleotide (NAD+) or its precursors that becomes available to the body’s cells to exert its functional effects. NAD+ is an essential coenzyme central to cellular energy metabolism and redox reactions, acting as a substrate for critical longevity-associated enzymes like sirtuins and PARPs. Optimizing its bioavailability is a significant focus in aging research and clinical longevity protocols.
Origin
The term originates from pharmacology and biochemistry, where “bioavailability” is a standard measure of a substance’s systemic absorption and utilization. The focus on NAD+ stems from the discovery of its pervasive role in cellular metabolism and the observation that NAD+ levels decline significantly with age. Research into various precursors, such as Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN), drives the contemporary discussion around optimizing this crucial molecule.
Mechanism
NAD+ is primarily synthesized through the salvage pathway from precursors, which must first be successfully absorbed from the digestive tract and then transported across cell membranes, a key determinant of bioavailability. Once inside the cell, NAD+ acts as an electron acceptor in the Krebs cycle, fueling ATP production, and as a substrate for sirtuins, which regulate gene expression and DNA repair. Hormonal signaling, particularly insulin sensitivity, can influence the activity of NAD+-consuming enzymes, thereby impacting the overall cellular pool and utilization rate.
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