Cited by 162Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsSirtuins and Resveratrol in Medicine

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Elimination of p19ARF-expressing cells enhances pulmonary function in mice

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Hashimoto, Michihiro, Asai, Azusa, Kawagishi, Hiroyuki, Mikawa, Ryuta, Iwashita, Yuji, Kanayama, Kazuki, Sugimoto, Kazushi, Sato, Tadashi, Maruyama, Mitsuo, Sugimoto, Masataka·2016·JCI Insight

DOI 10.1172/jci.insight.87732PMC PMC5033852

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Abstract

Senescent cells accumulate in many tissues as animals age and are considered to underlie several aging-associated pathologies. The tumor suppressors p19 ARF and p16 INK4a , both of which are encoded in the CDKN2A locus, play critical roles in inducing and maintaining permanent cell cycle arrest during cellular senescence. Although the elimination of p16 INK4a -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 ARF 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 ARF -expressing cells. The ablation of p19 ARF -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 ARF . Our results indicate that the aging-associated decline in lung function was, at least partly, attributed to p19 ARF and was recovered by eliminating p19 ARF -expressing cells.

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Authors: Hashimoto, M., Asai, A., Kawagishi, H., Mikawa, R., Iwashita, Y., Kanayama, K., Sugimoto, K., Sato, T., Maruyama, M., & Sugimoto, M.
Affiliations: National Center for Geriatrics and Gerontology (JP)
Department of Oncologic Pathology and
Mie University (JP)
Juntendo University (JP)
Corresponding author: Sugimoto, Masataka
ORCID: Hashimoto, Michihiro
Asai, Azusa
Kawagishi, Hiroyuki
Mikawa, Ryuta
Iwashita, Yuji
Kanayama, Kazuki
Sato, Tadashi
Maruyama, Mitsuo
Venue: JCI Insight
Publisher: American Society for Clinical Investigation
Published: 2016-08-04
Volume: 1
Issue: 12
Pages: e87732-e87732
ISSN: 2379-3708 (ISSN-L)
DOI: 10.1172/jci.insight.87732
PMC: PMC5033852
OpenAlex: W2497953377
Semantic Scholar: 09c297e32bfdab931b8cfc06cdce69f1fe3aea3e
Cited by: 162
References: 60
Citations by year: 2026: 10 · 2025: 11 · 2024: 15 · 2023: 16 · 2022: 12 · 2021: 23 · 2020: 20 · 2019: 21 · 2018: 19 · 2017: 15
FWCI: 14.76
Type: journal article
Language: en
Open access: gold
doi.org
Locations: JCI Insight (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Aichi Health Promotion Foundation
National Center for Geriatrics and Gerontology (28-22)
Japan Foundation for Aging and Health
Japan Society for the Promotion of Science (26461199, 16K08604)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords: cellular senescence, p19ARF, p16INK4a, CDKN2A, senolytics, senescent cell elimination, lung aging, lung function, lung compliance, tissue aging
MeSH terms: Aging, Animals, Lung, Mice, Inbred C57BL, Mice, Transgenic, Respiratory Function Tests, Cellular Senescence, Tumor Suppressor Protein p14ARF, Mice

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Elimination of p19ARF-expressing cells enhances pulmonary function in mice

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