Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 78, Issue 23, Pages 7757-7776Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-021-03980-x
Keywords
Stem cells; Senolysis; Senescence; Apoptosis; Stress resistance
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Funding
- Russian Science Foundation [19-74-10038]
- Russian Science Foundation [19-74-10038] Funding Source: Russian Science Foundation
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Cardiac glycosides have been shown to be effective senolytics, but they do not have senolytic ability towards senescent hMSCs from different origins. Senescent hMSCs avoid senolysis by increasing apoptosis resistance and weakening antiapoptotic defense.
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. [GRAPHICS] .
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