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

Juliana Camacho-Pereira, Mariana G. Tarragó, 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

Research output: Contribution to journalArticle

180 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1127-1139
Number of pages13
JournalCell Metabolism
Volume23
Issue number6
DOIs
StatePublished - Jun 14 2016

Keywords

  • CD38
  • NAD
  • aging
  • glucose intolerance
  • mitochondrial function

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Camacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., Puranik, A. S., Schoon, R. A., Reid, J. M., Galina, A., & Chini, E. N. (2016). CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metabolism, 23(6), 1127-1139. https://doi.org/10.1016/j.cmet.2016.05.006