RT Journal Article
T1 Identification and characterization of Cardiac Glycosides as senolytic compounds
A1 Triana-Martínez, Francisco
A1 Picallos-Rabina, Pilar
A1 Pietrocola, Federico
A1 Llanos, Susana
A1 Rodilla, Verónica
A1 Soprano, Enrica
A1 Pedrosa, Pablo
A1 Barradas, Marta
A1 Hernández-González, Fernanda
A1 Lalinde, Marta
A1 Prats, Neus
A1 Bernadó, Cristina
A1 González, Patricia
A1 Gómez, María
A1 Ikonomopoulou, Maria P.
A1 Fernández-Marcos, Pablo J.
A1 Arribas, Joaquín
A1 González-Barcia, Miguel
A1 Serrano, Manuel
A1 Domínguez, Eduardo
A1 Silva Álvarez, Sabela da
A1 Ferreirós, Alba
A1 García-Caballero Parada, Tomás
A1 Pino González de la Higuera, Pablo Alfonso del
A1 Vidal Figueroa, Anxo
A1 Loza García, María Isabel
A1 Collado Rodríguez, Manuel
AB 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.
PB Nature Research
YR 2019
FD 2019-10-21
LK https://hdl.handle.net/10347/44987
UL https://hdl.handle.net/10347/44987
LA eng
NO Triana-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-x
NO We 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). 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 Ramón 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.
DS Minerva
RD 28 abr 2026