NAD+

Nicotinamide adenine dinucleotide (NAD⁺) is a critical coenzyme found in every living cell, serving as a central mediator of cellular energy metabolism and a substrate for key signaling enzymes. NAD⁺ participates in over 500 enzymatic reactions, functioning as an electron carrier in glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. Beyond its role as a redox cofactor, NAD⁺ serves as a consumed substrate for sirtuins (SIRT1-7), poly(ADP-ribose) polymerases (PARPs), and CD38/CD157 ectoenzymes — all of which play critical roles in DNA repair, gene expression regulation, calcium signaling, and immune-cell research markers.

Research has established that NAD⁺ levels decline significantly with age, a phenomenon now recognized as a hallmark of aging biology. This decline is attributed to increased NAD⁺ consumption by activated PARPs and CD38 (which increase with chronic inflammation and DNA damage), combined with reduced biosynthesis. The resulting NAD⁺ depletion impairs sirtuin function — particularly SIRT1 and SIRT3 — leading to mitochondrial dysfunction, decreased oxidative metabolism, increased oxidative stress, and accelerated aging phenotypes. This understanding has positioned NAD⁺ repletion as a major research focus in geroscience.

Preclinical studies have demonstrated that restoring NAD⁺ levels — whether through direct NAD⁺ supplementation or via precursors like NMN and NR — reverses many age-related metabolic dysfunctions in animal models. Research by Sinclair and colleagues showed that NAD⁺ repletion in aged mouse research models restored mitochondrial-function markers to youthful-control levels and shifted muscle-function and metabolic-parameter readouts in preclinical studies. Preclinical and research studies investigating NAD⁺ and its precursors are ongoing, exploring applications in metabolic disease models, neurodegeneration, cardiovascular research, and aging biology.