NAD+: a crucial regulator of sirtuin activity in aging

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme involved in several redox reactions. NAD+ also serves as an important substrate for several enzymes associated with DNA repair, secondary messenger signaling, and transcriptional regulation. These NAD+-consuming enzymes include poly-ADP-ribose polymerases (PARPs), CD38/157 ectoenzymes, and histone deacetylases known as sirtuins. NAD+ levels have been shown to decline during the aging process in several murine models and human clinical studies. NAD+ depletion has been associated with deficits in nuclear and mitochondrial function leading to many age-associated pathologies. Maintaining cellular NAD+ anabolism by supplementing with NAD+ and its related precursors has been reported to attenuate age-related functional defects and improve overall quality of life. Sirtuins are thought to be partly responsible for the beneficial effects of NAD+ on the aging phenotype. Thus supplementation with NAD+ intermediates may be an efficacious therapeutic intervention to manipulate sirtuin function, improve health span and promote “healthy” aging, bringing hope to our growing aging societies both nationally and abroad.