CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism

Camacho-Pereira J, Tarragó MG, Chini CCS, et al. · Cell Metabolism

The NAD+-consuming enzyme CD38 increased in mouse tissues with age and was required for the age-related NAD+ decline and mitochondrial dysfunction (via SIRT3); CD38 was also identified as the main enzyme degrading NMN in vivo — the enzyme that rises with age destroys the supplement on its way to becoming NAD+.

Population

Aging wild-type and CD38-knockout mice; tissue and cell NAD+ measurements

Intervention

Genetic CD38 deletion; CD38 activity and expression profiling across age

Comparator

Young mice; wild-type mice

Limitations

General-tissue mouse aging biology; no joint endpoints; the NMN-degradation finding is mouse in-vivo pharmacology, untested in humans.