CD38 (NADase)
The enzyme that destroys your NAD+ and accelerates aging
Definition
CD38 is a membrane glycoprotein that acts as the main NAD+-consuming enzyme (NADase) in mammalian tissues. It degrades NAD+ and its precursors (such as NMN) to generate calcium-signaling molecules. Its expression rises sharply with age —driven by chronic low-grade inflammation (inflammaging)— precisely when the cell's capacity to synthesize NAD+ is already declining. This double hit makes CD38 a central driver of the age-related fall in NAD+ and of the mitochondrial dysfunction that accompanies it.
Detailed explanation
Eduardo Chini's group at the Mayo Clinic showed in 2016 (Cell Metabolism) that CD38 "dictates" the age-related NAD+ decline through a SIRT3-dependent mechanism: CD38 knockout mice retained youthful NAD+ levels at 32 months, whereas normal mice lost roughly half.
Mechanistically, CD38 hydrolyzes both NAD+ and its precursor NMN, limiting the effectiveness of replacement therapies (NAD+ IV, NMN, NR) if the enzyme stays hyperactive. Its age-related increase is largely explained by the accumulation of CD38-positive immune cells recruited by chronic tissue inflammation.
Inhibiting CD38 preserves NAD+ and reactivates pro-longevity pathways: sirtuins, AMPK, and more efficient mitochondrial function. The flavonoid apigenin (found in parsley, chamomile, and celery) was identified by Escande et al. (2013, Diabetes) as a natural CD38 inhibitor that raises intracellular NAD+. More potent synthetic inhibitors such as 78c reverse tissue NAD+ decline and improve metabolic function in animal models of aging.
Scientific sources
- PubMed — CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism (Camacho-Pereira, Chini — Cell Metabolism 2016)
- PubMed — Flavonoid apigenin is an inhibitor of the NAD+ase CD38 (Escande, Sinclair, Chini — Diabetes 2013)
- Source — A potent and specific CD38 inhibitor ameliorates age-related metabolic dysfunction by reversing tissue NAD+ decline (Tarragó, Chini — Cell Metabolism 2018)
- Source — Why NAD+ Declines during Aging: It's Destroyed (Schultz & Sinclair — Cell Metabolism 2016)
Related terms
Interested in related treatments?
Generate My Protocol