title: Elimination of p19ARF-expressing cells enhances pulmonary function in mice.
abstract: Senescent cells accumulate in many tissues as animals age and are considered to underlie several aging-associated pathologies. The tumor suppressors p19ARFand p16INK4a, both of which are encoded in theCDKN2Alocus, play critical roles in inducing and maintaining permanent cell cycle arrest during cellular senescence. Although the elimination of p16INK4a-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 p19ARFcontributes 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 p19ARF-expressing cells. The ablation of p19ARF-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 p19ARF. Our results indicate that the aging-associated decline in lung function was, at least partly, attributed to p19ARFand was recovered by eliminating p19ARF-expressing cells.
authors.affiliation: Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Asai
authors.affiliation: Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawagishi
authors.affiliation: Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Mikawa
authors.affiliation: Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Iwashita
authors.affiliation: Department of Oncologic Pathology and.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kanayama
authors.affiliation: Department of Molecular and Laboratory Medicine, Mie University School of Medicine, Tsu, Mie, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Maruyama
authors.affiliation: Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sugimoto
mesh_terms: D000375:Aging; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics*; D008168:Lung / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012129:Respiratory Function Tests; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
chemical_list: D025803:Tumor Suppressor Protein p14ARF