CD38 dictates age-related NAD decline and mitochondrial dysfunction through a SIRT3-dependent mechanism

By Juliana Camacho-Pereira, M. Tarragó, Claudia C S Chini, Verónica Nin, C. Escande, G. Warner, A. Puranik, R. A. Schoon, J. Reid, A. Galina and 1 more. Cell Metabolism, 2016

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Summary 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.

Subfields: Electrical and Electronic Engineering, Geriatrics and Gerontology, Physiology

View Paper: https://www.semanticscholar.org/paper/fd33939a6497a322a48dac8a43bcb878368edb0a

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Citations in the corpus

NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential (2020, background): “However, another study describes no alteration of the NAMPT mRNA or protein levels in aged mice and human tissues.(52) Thus, these controversial findings of NAMPT-catalyzed NAD biosynthesis overage might come from the differential cell type and tissue context, which will be elucidated in future stud”
Mitochondrial dysfunction in cell senescence and aging (2022, background): “In mammals, three members of the SIRT family, SIRT3, SIRT4, and SIRT5, are localized in mitochondria and modulate mitochondrial metabolism (88).”
Therapeutic potential of NAD-boosting molecules: the in vivo evidence (2018, positive): “Recent advancements in high-resolution, high-sensitivity NAD+ metabolite tracing methods such as mitoPARP, PARAPLAY, and ApolloNADP+ (Cambronne et al., 2016; Cameron et al., 2016; Dölle et al., 2010) have revealed that the concentration and distribution of NAD+ and its metabolites are different dep”