The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Elimination of p19ARF-expressing cells enhances pulmonary function in mice
Open accessAbstract
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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“Converging evidence suggests that the aging hallmark, cellular senescence, may be a central mechanism contributing to IPF [6,7].”
From Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study (2019) · cites this paper as [7]
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“Very recently, Hashimoto et al. provided crucial evidence that cellular senescence contributes to lung ageing and may be targeted for functional improvement20.”
From Cellular senescence mediates fibrotic pulmonary disease (2017) · cites this paper as [20]
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“cellular senescence has emerged as the nexus between chronological aging and deficits in the structure and function of multiple organs”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Hashimoto et al., 2016
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Metadata
- 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
- Venue
- JCI Insight
- Published
- 2016-08-04
- Volume
- 1
- Issue
- 12
- Pages
- e87732-e87732
- ISSN
- 2379-3708 (ISSN-L)
- 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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