Senescent cells promote NAD tissue decline during aging through CD38 enzymes which can now become a novel therapeutic target.
Nicotinamide adenine dinucleotide (NAD) is a crucial metabolic coenzyme and reducing cofactor for oxidising enzymes such as poly-ADP-ribose polymerases (PARPs). Low levels of NAD have been linked to aging diseases and more recently it has been established that natural NAD levels decrease with age – yet the mechanisms behind the pathogenic effects of decreasing NAD remain elusive.
NAD can be made in the body in two ways: through the de novo pathway from tryptophan or the salvage pathway from precursor vitamins nicotinamide (NAM), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). The levels of NAD are therefore dependent on synthesis, metabolic consumption, as well as NAD hydrolase enzymes such as CD38 and CD157.
A study by Camacho-Periera et al. found that CD38 specifically dictates age-related NAD decline and mitochondrial dysfunction, one hallmark of aging.