biostudies-literatureDeryabin PIrussian science foundation7757-7776https://www.ebi.ac.uk/biostudies/studies/S-EPMC8629786biostudies-literatureUnknown78(23)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 charCellular and molecular life sciences : CMLSApoptosis resistance of senescent cells is an intrinsic barrier for senolysis induced by cardiac glycosides.PMC862978619-74-10038Shatrova ANBorodkina AVDeryabin PIfalseApoptosis resistance of senescent cells is an intrinsic barrier for senolysis induced by cardiac glycosides.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 char2021-01-01T00:00:00Z2021 Dec2026-05-06T03:21:46.239Z2022-02-11T14:20:57.31ZS-EPMC86297863471435810.1007/s00018-021-03980-x