Apoptosis resistance of senescent cells is an intrinsic barrier for senolysis induced by cardiac glycosides.
Apoptosis resistance of senescent cells is an intrinsic barrier for senolysis induced by cardiac glycosides.
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DOI：
10.1007/s00018-021-03980-x
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Borodkina AV
中科院分区：
文献类型：
--
作者：
Deryabin PI;Shatrova AN;Borodkina AV
靶向消除衰老细胞，即衰老溶解，是抗衰老治疗的核心趋势之一。强心苷最近被证明是一种广谱抗衰老药。在这里，我们测试了强心苷对人间充质干细胞 (hMSC) 的抗衰老特性。强心苷对各种来源的衰老 hMSC 没有抗衰老能力。使用生物学和生物信息学方法，我们比较了“强心苷敏感”A549 和“不敏感”hMSC 的衰老发育。发现衰老作用的缺失是由衰老 hMSC 中有效的钾输入和细胞凋亡抵抗力增加介导的。 “抗凋亡防御”的减弱使 hMSC 易于衰老。我们发现，之前被认为是衰老的共同特征的细胞凋亡抵抗实际上并不是衰老细胞的普遍特征。此外，只有易凋亡的衰老细胞对强心苷诱导的衰老作用敏感。因此，我们可以推测，衰老作用的有效性可能取决于衰老细胞与增殖细胞相比是否确实具有抗凋亡能力。在线版本包含可在 10.1007/s00018-021-03980-x 获取的补充材料。
Targeted elimination of senescent cells, senolysis, is one of the core trends in the anti-aging therapy. Cardiac glycosides were recently proved to be a broad-spectrum senolytics. Here we tested senolytic properties of cardiac glycosides towards human mesenchymal stem cells (hMSCs). Cardiac glycosides had no senolytic ability towards senescent hMSCs of various origins. Using biological and bioinformatic approaches we compared senescence development in ‘cardiac glycosides-sensitive’ A549 and ‘-insensitive’ hMSCs. The absence of senolysis was found to be mediated by the effective potassium import and increased apoptosis resistance in senescent hMSCs. Weakening “antiapoptotic defense” predisposes hMSCs to senolysis. We revealed that apoptosis resistance, previously recognized as a common characteristic of senescence, in fact, is not a general feature of senescent cells. Moreover, only apoptosis-prone senescent cells are sensitive to cardiac glycosides-induced senolysis. Thus, we can speculate that the effectiveness of senolysis might depend on whether senescent cells indeed become apoptosis-resistant as compared to their proliferating counterparts. The online version contains supplementary material available at 10.1007/s00018-021-03980-x.
影响因子：
5.4
作者：
Wang Z;Gao J;Liu H;Ohno Y;Xu C
通讯作者：
Xu C