Elimination of p19 ARF -expressing cells enhances pulmonary function in mice

Senescent cells accumulate in many tissues as animals age and are considered to underlie several aging-associated pathologies. The tumor suppressors p19 and p16 , both of which are encoded in the locus, play critical roles in inducing and maintaining permanent cell cycle arrest during cellular senes...

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Bibliographic Details
Published in:JCI insight 2016-08, Vol.1 (12), p.e87732
Main Authors: Hashimoto, Michihiro, Asai, Azusa, Kawagishi, Hiroyuki, Mikawa, Ryuta, Iwashita, Yuji, Kanayama, Kazuki, Sugimoto, Kazushi, Sato, Tadashi, Maruyama, Mitsuo, Sugimoto, Masataka
Format: Article
Language:English
Subjects:
Aging
Animals
Cellular Senescence - genetics
Lung - physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Respiratory Function Tests
Tumor Suppressor Protein p14ARF - genetics
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Summary:Senescent cells accumulate in many tissues as animals age and are considered to underlie several aging-associated pathologies. The tumor suppressors p19 and p16 , both of which are encoded in the locus, play critical roles in inducing and maintaining permanent cell cycle arrest during cellular senescence. Although the elimination of p16 -expressing cells extends the life span of the mouse, it is unclear whether tissue function is restored by the elimination of senescent cells in aged animals and whether and how p19 contributes to tissue aging. The aging-associated decline in lung function is characterized by an increase in compliance as well as pathogenic susceptibility to pulmonary diseases. We herein demonstrated that pulmonary function in 12-month-old mice was reversibly restored by the elimination of p19 -expressing cells. The ablation of p19 -expressing cells using a toxin receptor-mediated cell knockout system ameliorated aging-associated lung hypofunction. Furthermore, the aging-associated gene expression profile was reversed after the elimination of p19 . Our results indicate that the aging-associated decline in lung function was, at least partly, attributed to p19 and was recovered by eliminating p19 -expressing cells.
ISSN:2379-3708
2379-3708