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dc.contributor.authorTriana-Martínez, Francisco
dc.contributor.authorPicallos-Rabina, Pilar
dc.contributor.authorDa Silva-Álvarez, Sabela
dc.contributor.authorPietrocola, Federico
dc.contributor.authorLLanos, Susana 
dc.contributor.authorRodilla, Verónica
dc.contributor.authorSoprano, Enrica
dc.contributor.authorPedrosa, Pablo
dc.contributor.authorFerreirós, Alba
dc.contributor.authorBarradas, Marta
dc.contributor.authorHernández-González, Fernanda
dc.contributor.authorLalinde, Marta
dc.contributor.authorPrats, Neus
dc.contributor.authorBernadó, Cristina
dc.contributor.authorGonzalez, Patricia 
dc.contributor.authorGómez, María
dc.contributor.authorIkonomopoulou, Maria P
dc.contributor.authorFernández-Marcos, Pablo J
dc.contributor.authorGarcía-Caballero, Tomás
dc.contributor.authorDel Pino, Pablo
dc.contributor.authorArribas, Joaquín
dc.contributor.authorVidal, Anxo
dc.contributor.authorGonzález-Barcia, Miguel
dc.contributor.authorSerrano Marugan, Manuel 
dc.contributor.authorLoza, María I
dc.contributor.authorDomínguez, Eduardo
dc.contributor.authorCollado, Manuel
dc.date.accessioned2020-03-24T18:51:46Z
dc.date.available2020-03-24T18:51:46Z
dc.date.issued2019-10-21
dc.identifier.citationNat Commun. 2019;10(1):4731es_ES
dc.identifier.issn2041-1723es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9318
dc.description.abstractCompounds 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.es_ES
dc.description.sponsorshipWe thank Matthias Drosten, Alejo Efeyan and Sean Morrison for plasmids. F.T-M. is a postdoctoral fellow from CONACYT (cvu 268632); P.P. is a predoctoral fellow from Xunta de Galicia; M.C. is a "Miguel Servet II" investigator (CPII16/00015). P.P.-R. receives support from a program by the Deputacion de Coruna (BINV-CS/2019). Work in the laboratory of M.C. is funded by grant RTI2018-095818-B-100 (MCIU/AEI/FEDER, UE). P.J.F.-M. is funded by the IMDEA Food Institute, the Ramon Areces Foundation, (CIVP18A3891), and a Ramon y Cajal Award (MICINN) (RYC-2017-22335). M.P.I. is funded by Talento Modalidad-1 Program Grant, Madrid Regional Government (#2018-T1/BIO-11262). F.P. was funded by a Long Term EMBO Fellowship (ALTF-358-2017) and F.H-G. was funded by the PhD4MD Programme of the IRB, Hospital Clinic and IDIBAPS. Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and "laCaixa" Foundation.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Group es_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshA549 Cells es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntibiotics, Antineoplastices_ES
dc.subject.meshApoptosis es_ES
dc.subject.meshBleomycin es_ES
dc.subject.meshBreast Neoplasms es_ES
dc.subject.meshCardiac Glycosides es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshCell Membrane es_ES
dc.subject.meshCellular Senescence es_ES
dc.subject.meshChondrocytes es_ES
dc.subject.meshDigoxin es_ES
dc.subject.meshFemale es_ES
dc.subject.meshFibroblasts es_ES
dc.subject.meshHumans es_ES
dc.subject.meshHydrogen-Ion Concentration es_ES
dc.subject.meshMice es_ES
dc.subject.meshOsteoarthritis es_ES
dc.subject.meshOuabain es_ES
dc.subject.meshProscillaridin es_ES
dc.subject.meshPulmonary Fibrosis es_ES
dc.subject.meshXenograft Model Antitumor Assays es_ES
dc.titleIdentification and characterization of Cardiac Glycosides as senolytic compoundses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID31636264es_ES
dc.format.volume10es_ES
dc.format.number1es_ES
dc.format.page4731es_ES
dc.identifier.doi10.1038/s41467-019-12888-xes_ES
dc.contributor.funderIMDEA Food Institute
dc.contributor.funderFundación Ramón Areces 
dc.contributor.funderFundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal 
dc.contributor.funderEuropean Molecular Biology Organization 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderUnión Europea 
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) 
dc.contributor.funderFundación La Caixa 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-019-12888-x.es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Telómeros y Telomerasaes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2013-48256-Res_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/EC/H2020/669622es_ES
dc.rights.accessRightsopen accesses_ES


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Este Item está sujeto a una licencia Creative Commons: Atribución-NoComercial-CompartirIgual 4.0 Internacional