Tier 4 — mechanistic

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

Camacho-Pereira J, Tarrago MG, Chini CCS, Nin V, Escande C, Warner GM, Puranik AS, Schoon RA, Reid JM, Galina A, Chini EN
Cell Metabolism 2016 23(6):1127-1139

Bibliography

PubMed
PMID 27304511
DOI
10.1016/j.cmet.2016.05.006
Funding
Not stated in the available abstract.
Competing interests
Not stated in the available abstract.

Study snapshot

DesignIn vivo mouse mechanistic study
ModelMice (aged vs young; CD38 knockout)
SampleNot applicable (animal study)
InterventionCD38 genetic knockout; NMN administration to test CD38-mediated NMN degradation
DurationNot applicable (cross-sectional aging comparison)
EndpointsTissue NAD levels with age; Mitochondrial function (SIRT3-dependent); CD38-mediated degradation of NMN

What the study showed, in plain terms

This mouse study explains why NAD levels fall with age. It shows that the enzyme CD38 becomes more active as mice age, and this rising CD38 activity is a major reason NAD declines and mitochondria work less well. The study also shows CD38 breaks down NMN, a popular NAD-boosting supplement ingredient, which is relevant to anyone combining NAD precursors with a CD38 inhibitor.

Key findings

CD38 expression and activity increase with age in mice, and CD38 is required for the age-related decline in NAD and the resulting mitochondrial dysfunction, acting at least in part through a SIRT3-dependent pathway. CD38 was also identified as the main enzyme responsible for degrading the NAD precursor nicotinamide mononucleotide (NMN) in vivo, meaning CD38 activity affects how much benefit is obtained from NMN-based NAD-replacement strategies.

What this study can and cannot tell us

This is a mouse mechanistic study; it does not test apigenin or any other CD38 inhibitor as an intervention, and it does not include human data. It establishes the CD38-aging-NAD link that motivates interest in CD38 inhibitors, but does not itself demonstrate a therapeutic effect.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology