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 language | English (US) |
|---|---|
| Pages (from-to) | 1127-1139 |
| Number of pages | 13 |
| Journal | Cell Metabolism |
| Volume | 23 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 14 2016 |
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Keywords
- aging
- CD38
- glucose intolerance
- mitochondrial function
- NAD
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Physiology
Cite this
CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. / Camacho-Pereira, Juliana; Tarragó, Mariana G.; Chini, Claudia C S; Nin, Veronica; Escande, Carlos; Warner, Gina M.; Puranik, Amrutesh S.; Schoon, Renee A.; Reid, Joel M; Galina, Antonio; Chini, Eduardo Nunes.
In: Cell Metabolism, Vol. 23, No. 6, 14.06.2016, p. 1127-1139.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism
AU - Camacho-Pereira, Juliana
AU - Tarragó, Mariana G.
AU - Chini, Claudia C S
AU - Nin, Veronica
AU - Escande, Carlos
AU - Warner, Gina M.
AU - Puranik, Amrutesh S.
AU - Schoon, Renee A.
AU - Reid, Joel M
AU - Galina, Antonio
AU - Chini, Eduardo Nunes
PY - 2016/6/14
Y1 - 2016/6/14
N2 - 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.
AB - 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.
KW - aging
KW - CD38
KW - glucose intolerance
KW - mitochondrial function
KW - NAD
UR - http://www.scopus.com/inward/record.url?scp=84975472602&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84975472602&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2016.05.006
DO - 10.1016/j.cmet.2016.05.006
M3 - Article
VL - 23
SP - 1127
EP - 1139
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 6
ER -