Identification and characterization of Cardiac Glycosides as senolytic compounds

Nat Commun. 2019 Oct 21;10(1):4731. doi: 10.1038/s41467-019-12888-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis / drug effects*
  • Bleomycin / pharmacology
  • Breast Neoplasms
  • Cardiac Glycosides / pharmacology*
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cellular Senescence / drug effects*
  • Chondrocytes / drug effects*
  • Digoxin / pharmacology
  • Female
  • Fibroblasts / drug effects*
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Mice
  • Osteoarthritis
  • Ouabain / pharmacology
  • Proscillaridin / pharmacology
  • Pulmonary Fibrosis
  • Xenograft Model Antitumor Assays


  • Antibiotics, Antineoplastic
  • Cardiac Glycosides
  • Bleomycin
  • Ouabain
  • Digoxin
  • Proscillaridin