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

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2016 Jun 16

PMID 27304511

Citations 401

Authors

Juliana Camacho-Pereira

Mariana G Tarrago

Claudia C S Chini

Veronica Nin

Carlos Escande

Gina M Warner

Amrutesh S Puranik

Renee A Schoon

Joel M Reid

Antonio Galina

Eduardo N Chini

Affiliations

Soon will be listed here.

Abstract

Nicotinamide adenine dinucleotide (NAD) levels decrease during aging and are involved in age-related metabolic decline. To date, the mechanism responsible for the age-related reduction in NAD has not been elucidated. Here we demonstrate that expression and activity of the NADase CD38 increase with aging and that CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by regulation of SIRT3 activity. We also identified CD38 as the main enzyme involved in the degradation of the NAD precursor nicotinamide mononucleotide (NMN) in vivo, indicating that CD38 has a key role in the modulation of NAD-replacement therapy for aging and metabolic diseases.

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