Format

Send to

Choose Destination
Cell Metab. 2016 Jun 14;23(6):1127-1139. doi: 10.1016/j.cmet.2016.05.006.

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

Author information

1
Signal Transduction Laboratory, Kogod Aging Center, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ 21941-590, Brazil.
2
Signal Transduction Laboratory, Kogod Aging Center, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
3
Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
4
Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ 21941-590, Brazil.
5
Signal Transduction Laboratory, Kogod Aging Center, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. Electronic address: chini.eduardo@mayo.edu.

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.

KEYWORDS:

CD38; NAD(+); aging; glucose intolerance; mitochondrial function

PMID:
27304511
PMCID:
PMC4911708
DOI:
10.1016/j.cmet.2016.05.006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center