NAD+

Nicotinamide adenine dinucleotide (NAD⁺) is a ubiquitous pyridine-nucleotide coenzyme present in every living cell, where it serves a dual role as an electron carrier in oxidative metabolism (the NAD⁺/NADH redox couple supports glycolysis, the citric-acid cycle, and oxidative phosphorylation) and as the obligate co-substrate of three families of signalling enzymes: the sirtuins (NAD⁺-dependent protein deacetylases), the PARPs (poly-ADP-ribose polymerases), and the cADP-ribose synthases (CD38, CD157). NAD⁺ is synthesised through three convergent pathways: de novo synthesis from tryptophan via the kynurenine pathway, the Preiss-Handler pathway from nicotinic acid, and the salvage pathway from nicotinamide via NAMPT. Cellular NAD⁺ concentration declines with age across multiple tissues — driven by reduced biosynthesis, increased CD38 expression, and increased PARP activation in response to accumulating DNA damage — producing impaired sirtuin activity, reduced mitochondrial function, and the metabolic phenotype of cellular ageing. NAD⁺ precursor supplementation (nicotinamide mononucleotide NMN, nicotinamide riboside NR) is the principal pharmacological strategy to reverse age-related NAD⁺ decline and is a focus of longevity research that overlaps with the mitochondrial-peptide field (MOTS-c, Humanin, SS-31).