NAD+

NAD+'s role as a metabolic redox cofactor has been established biochemistry since the early 20th century, but research interest accelerated substantially after the discovery that sirtuins — enzymes linked to caloric-restriction-associated longevity in model organisms — require NAD+ as an obligate substrate. This connected cellular NAD+ status directly to aging biology research.

Imai, Guarente, and others established that NAD+ levels decline with age across multiple tissues in animal models, and that this decline correlates with reduced sirtuin activity and impaired mitochondrial function. Cantó, Auwerx, and colleagues (2015, Cell Metabolism) reviewed the broader network of NAD+-dependent metabolic processes and the rationale for NAD+ or NAD+-precursor research.

Because directly administered NAD+ has practical limitations (poor cell permeability, rapid extracellular metabolism), much current research has shifted toward NAD+ precursor compounds — nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and others — that are more readily taken up by cells and converted to NAD+ intracellularly. Clinical research on both direct NAD+ administration (commonly via intravenous infusion in research and wellness settings) and precursor compounds is ongoing; as of current published literature, effects in healthy humans remain an active area of investigation rather than an established clinical intervention.