Triana-Martínez, FranciscoPicallos-Rabina, PilarPietrocola, FedericoLlanos, SusanaRodilla, VerónicaSoprano, EnricaPedrosa, PabloBarradas, MartaHernández-González, FernandaLalinde, MartaPrats, NeusBernadó, CristinaGonzález, PatriciaGómez, MaríaIkonomopoulou, Maria P.Fernández-Marcos, Pablo J.Arribas, JoaquínGonzález-Barcia, MiguelSerrano, ManuelDomínguez, EduardoSilva Álvarez, Sabela daFerreirós, AlbaGarcía-Caballero Parada, TomásPino González de la Higuera, Pablo Alfonso delVidal Figueroa, AnxoLoza García, María IsabelCollado Rodríguez, Manuel2026-01-092026-01-092019-10-21Triana-Martínez, F., Picallos-Rabina, P., Da Silva-Álvarez, S. et al. Identification and characterization of Cardiac Glycosides as senolytic compounds. Nat Commun 10, 4731 (2019). https://doi.org/10.1038/s41467-019-12888-xhttps://hdl.handle.net/10347/44987Compounds 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.engThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article10.1038/s41467-019-12888-x2041-1723open access