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Publication : Elimination of p19<sup>ARF</sup> -expressing cells protects against pulmonary emphysema in mice.

First Author  Mikawa R Year  2018
Journal  Aging Cell Volume  17
Issue  5 Pages  e12827
PubMed ID  30058137 Mgi Jnum  J:265452
Mgi Id  MGI:6200443 Doi  10.1111/acel.12827
Citation  Mikawa R, et al. (2018) Elimination of p19(ARF) -expressing cells protects against pulmonary emphysema in mice. Aging Cell 17(5):e12827
abstractText  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 p19(ARF) -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 p19(ARF) facilitated the development of pulmonary emphysema in mice. The elimination of p19(ARF) -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.
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