The NADase CD38 is induced by factors secreted from senescent cells providing a potential link between senescence and age-related cellular NAD+ decline
The NADase CD38 is induced by factors secreted from senescent cells providing a potential link between senescence and age-related cellular NAD+ decline
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DOI：
10.1016/j.bbrc.2019.03.199
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发表时间：
2019-05-28
影响因子：
3.1
通讯作者：
Chini, Eduardo
中科院分区：
文献类型：
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作者：
Chini, Claudia;Hogan, Kelly A.;Chini, Eduardo
组织烟酰胺腺嘌呤二核苷酸（NAD（+））的下降与衰老有关。我们最近发现CD 38是衰老过程中组织NAD（+）下降的中心调节因子。CD 38是一种在内皮细胞和炎症细胞中高度表达的胞外酶。迄今为止，在以衰老细胞的存在为特征的衰老组织中调节CD 38表达的机制尚未完全理解。细胞衰老被描述为衰老过程的标志，已知这些细胞通过其衰老相关分泌表型（SASP）分泌多种因子，包括细胞因子和趋化因子。在这里，我们研究了细胞衰老表型是否参与CD 38表达及其NAD酶活性的调节。我们观察到衰老细胞不具有CD 38的高表达。然而，由衰老细胞分泌的SASP因子诱导了非衰老细胞如内皮细胞或骨髓源性巨噬细胞中的CD 38 mRNA和蛋白表达，并增加了CD 38-NAD酶活性。我们的数据表明细胞衰老和NAD（+）下降之间存在联系，其中SASP介导的CD 38上调可破坏细胞NAD（+）稳态。(C)2019作者爱思唯尔公司出版
Tissue nicotinamide adenine dinucleotide (NAD(+)) decline has been implicated in aging. We have recently identified CD38 as a central regulator involved in tissue NAD(+) decline during the aging process. CD38 is an ecto-enzyme highly expressed in endothelial and inflammatory cells. To date, the mechanisms that regulate CD38 expression in aging tissues characterized by the presence of senescent cells is not completely understood. Cellular senescence has been described as a hallmark of the aging process and these cells are known to secrete several factors including cytokines and chemokines through their senescent associated secretory phenotype (SASP). Here we investigated if the cellular senescence phenotype is involved in the regulation of CD38 expression and its NADase activity. We observed that senescent cells do not have high expression of CD38. However, the SASP factors secreted by senescent cells induced CD38 mRNA and protein expression and increased CD38-NADase activity in non-senescent cells such as endothelial cells or bone marrow derived macrophages. Our data suggest a link between cellular senescence and NAD(+) decline in which SASP-mediated upregulation of CD38 can disrupt cellular NAD(+) homeostasis. (C) 2019 The Authors. Published by Elsevier Inc.