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Apoptosis resistance of senescent cells is an intrinsic barrier for senolysis induced by cardiac glycosides
Cell Mol Life Sci. 2021 Oct 29. doi: 10.1007/s00018-021-03980-x.
Pavel I Deryabin 1, Alla N Shatrova 2, Aleksandra V Borodkina 3
Abstract:
...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.
PMID: 34714358
Free Full-Text: https://link.springer.com/article/10.1007%2Fs00018-021-03980-x
Tags: apoptosis, Cardiac glycosides, senolytics