Scientific Glossary

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NAD+ declines significantly with aging (up to 50% reduction by middle age). Functions as an electron carrier in cellular respiration (converting to NADH), a substrate for sirtuin deacetylases (SIRT1-7), and a substrate for PARP enzymes involved in DNA repair. NAD+ supplementation research focuses on precursors (NMN, NR) and direct IV/IM administration. Research shows NAD+ precursor supplementation increases tissue NAD+ levels in humans, though functional outcomes vary by study.

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NMN is phosphorylated to NMN-dinucleotide (NMND) and then to NAD+ inside cells. As a direct precursor, NMN can raise NAD+ faster than more distal precursors like tryptophan. Human trials have demonstrated that oral NMN supplementation significantly elevates NAD+ metabolites in blood and muscle tissue. Japanese RCT (Igarashi 2022): 250mg/day NMN improved muscle insulin sensitivity and physical performance metrics in older adults. Note: NMN vs. NR (nicotinamide riboside) comparative research is ongoing.

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Sirtuins require NAD+ as a cosubstrate to function, linking cellular energy status to epigenetic regulation. SIRT1 activates PGC-1α (mitochondrial biogenesis), FOXO transcription factors (stress resistance), and p53 (DNA repair). SIRT3 maintains mitochondrial function. SIRT6 is essential for DNA double-strand break repair and telomere maintenance. Declining NAD+ with age reduces sirtuin activity, contributing to the aging phenotype. NAD+ precursor supplementation research aims to restore sirtuin activity as a longevity intervention.