Elimination of p19 ARF -expressing cells protects against pulmonary emphysema in mice

Aging Cell. 2018 Oct;17(5):e12827. doi: 10.1111/acel.12827. Epub 2018 Jul 30.


Senescent cells accumulate in tissues during aging and are considered to underlie several aging-associated phenotypes and diseases. We recently reported that the elimination of p19ARF -expressing senescent cells from lung tissue restored tissue function and gene expression in middle-aged (12-month-old) mice. The aging of lung tissue increases the risk of pulmonary diseases such as emphysema, and cellular senescence is accelerated in emphysema patients. However, there is currently no direct evidence to show that cellular senescence promotes the pathology of emphysema, and the involvement of senescence in the development of this disease has yet to be clarified. We herein demonstrated that p19ARF facilitated the development of pulmonary emphysema in mice. The elimination of p19ARF -expressing cells prevented lung tissue from elastase-induced lung dysfunction. These effects appeared to depend on reduced pulmonary inflammation, which is enhanced after elastase stimulation. Furthermore, the administration of a senolytic drug that selectively kills senescent cells attenuated emphysema-associated pathologies. These results strongly suggest the potential of senescent cells as therapeutic/preventive targets for pulmonary emphysema.

Keywords: SASP; cell ablation; cellular senescence; p19ARF; pulmonary emphysema; senolytic drug.

MeSH terms

  • Aniline Compounds / pharmacology
  • Animals
  • Bronchoalveolar Lavage Fluid
  • Cellular Senescence
  • Cyclin-Dependent Kinase Inhibitor p19 / metabolism*
  • Cytoprotection*
  • Diphtheria Toxin / metabolism
  • Female
  • Heparin-binding EGF-like Growth Factor / metabolism
  • Lung / pathology
  • Mice, Inbred C57BL
  • Pancreatic Elastase
  • Pulmonary Emphysema / metabolism*
  • Pulmonary Emphysema / pathology*
  • Sulfonamides / pharmacology
  • Swine


  • Aniline Compounds
  • Cyclin-Dependent Kinase Inhibitor p19
  • Diphtheria Toxin
  • Heparin-binding EGF-like Growth Factor
  • Sulfonamides
  • Pancreatic Elastase
  • navitoclax