2026-06-14T03:32:18Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/93182024-11-29T17:54:28Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
IMDEA Food Institute
funder
Fundación Ramón Areces
funder
Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal
funder
European Molecular Biology Organization
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Fundación La Caixa
2020-03-24T18:51:46Z
2020-03-24T18:51:46Z
2019-10-21
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
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.
eng
Identification and characterization of Cardiac Glycosides as senolytic compounds
journal article
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