2026-06-14T03:36:01Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/93182024-11-29T17:54:28Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Triana-Martínez, Francisco author Picallos-Rabina, Pilar author Da Silva-Álvarez, Sabela author Pietrocola, Federico author LLanos, Susana author Rodilla, Verónica author Soprano, Enrica author Pedrosa, Pablo author Ferreirós, Alba author Barradas, Marta author Hernández-González, Fernanda author Lalinde, Marta author Prats, Neus author Bernadó, Cristina author Gonzalez, Patricia author Gómez, María author Ikonomopoulou, Maria P author Fernández-Marcos, Pablo J author García-Caballero, Tomás author Del Pino, Pablo author Arribas, Joaquín author Vidal, Anxo author González-Barcia, Miguel author Serrano Marugan, Manuel author Loza, María I author Domínguez, Eduardo author Collado, Manuel author 2019-10-21 Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases. Nat Commun. 2019;10(1):4731 10.1038/s41467-019-12888-x 2041-1723 2041-1723 Nature communications 31636264 http://hdl.handle.net/20.500.12105/9318 Identification and characterization of Cardiac Glycosides as senolytic compounds