CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD(+) and NMN levels.
CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD(+) and NMN levels.
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DOI：
10.1038/s42255-020-00298-z
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发表时间：
2020-11
影响因子：
20.8
通讯作者：
Chini EN
中科院分区：
文献类型：
--
作者：
Chini CCS;Peclat TR;Warner GM;Kashyap S;Espindola-Netto JM;de Oliveira GC;Gomez LS;Hogan KA;Tarragó MG;Puranik AS;Agorrody G;Thompson KL;Dang K;Clarke S;Childs BG;Kanamori KS;Witte MA;Vidal P;Kirkland AL;De Cecco M;Chellappa K;McReynolds MR;Jankowski C;Tchkonia T;Kirkland JL;Sedivy JM;van Deursen JM;Baker DJ;van Schooten W;Rabinowitz JD;Baur JA;Chini EN
烟酰胺腺嘌呤二核苷酸（NAD⁺）水平降低已被证明在衰老过程中会导致代谢功能障碍。通过敲除CD38酶可部分阻止NAD⁺的下降。然而，在衰老过程中CD38是如何被调控的，以及其胞外酶活性如何影响NAD⁺稳态尚不明确。在此我们表明，衰老过程中白色脂肪组织（WAT）和肝脏中CD38的增加是由CD38⁺免疫细胞的积累所介导的。炎症会使CD38增加，NAD⁺降低。此外，衰老细胞及其分泌的信号会促进白色脂肪组织中CD38⁺细胞的积累，清除衰老细胞或其分泌表型会使CD38减少，部分逆转NAD⁺的下降。最后，阻断CD38的胞外酶活性可通过烟酰胺单核苷酸（NMN）依赖的过程使NAD⁺增加。我们的研究结果表明，衰老诱导的炎症促进免疫细胞中CD38的积累，而CD38通过其胞外酶活性降低NMN和NAD⁺的水平。
Decreased nicotinamide adenine dinucleotide (NAD+) levels have been shown to contribute to metabolic dysfunction during aging. NAD+ decline can be partially prevented by knockout of the enzyme CD38. However, it is not known how CD38 is regulated during aging, and how its ecto-enzymatic activity impacts NAD+ homeostasis. Here we show that increases in CD38 in white adipose tissue (WAT) and liver during aging is mediated by accumulation of CD38+ immune cells. Inflammation increases CD38 and decreases NAD+. In addition, senescent cells and their secreted signals promote accumulation of CD38+ cells in WAT, and ablation of senescent cells or their secretory phenotype decrease CD38, partially reversing NAD+ decline. Finally, blocking the ecto-enzymatic activity of CD38 can increase NAD+ through a nicotinamide mononucleotide (NMN)-dependent process. Our findings demonstrate that senescence-induced inflammation promotes accumulation of CD38 in immune cells that through its ecto-enzymatic activity decreases levels of NMN and NAD+.
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影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
7.3
作者：
Becherer, J. David;Boros, Eric E.;Ulrich, John C.
通讯作者：
Ulrich, John C.
DOI：
10.1016/j.bbrc.2019.03.199
发表时间：
2019-05-28
影响因子：
3.1
作者：
Chini, Claudia;Hogan, Kelly A.;Chini, Eduardo
通讯作者：
Chini, Eduardo
影响因子：
29
作者：
Chatterjee S;Daenthanasanmak A;Chakraborty P;Wyatt MW;Dhar P;Selvam SP;Fu J;Zhang J;Nguyen H;Kang I;Toth K;Al-Homrani M;Husain M;Beeson G;Ball L;Helke K;Husain S;Garrett-Mayer E;Hardiman G;Mehrotra M;Nishimura MI;Beeson CC;Bupp MG;Wu J;Ogretmen B;Paulos CM;Rathmell J;Yu XZ;Mehrotra S
通讯作者：
Mehrotra S
影响因子：
20.8
作者：
Covarrubias AJ;Kale A;Perrone R;Lopez-Dominguez JA;Pisco AO;Kasler HG;Schmidt MS;Heckenbach I;Kwok R;Wiley CD;Wong HS;Gibbs E;Iyer SS;Basisty N;Wu Q;Kim IJ;Silva E;Vitangcol K;Shin KO;Lee YM;Riley R;Ben-Sahra I;Ott M;Schilling B;Scheibye-Knudsen M;Ishihara K;Quake SR;Newman J;Brenner C;Campisi J;Verdin E
通讯作者：
Verdin E