Age-Related Changes in the Cellular Composition and Epithelial Organization of the Mouse Trachea
Open accessAbstract
We report here senescent changes in the structure and organization of the mucociliary pseudostratified epithelium of the mouse trachea and main stem bronchi. We confirm previous reports of the gradual appearance of age-related, gland-like structures (ARGLS) in the submucosa, especially in the intercartilage regions and carina. Immunohistochemistry shows these structures contain ciliated and secretory cells and Krt5+ basal cells, but not the myoepithelial cells or ciliated ducts typical of normal submucosal glands. Data suggest they arise de novo by budding from the surface epithelium rather than by delayed growth of rudimentary or cryptic submucosal glands. In old mice the surface epithelium contains fewer cells per unit length than in young mice and the proportion of Krt5+, p63+ basal cells is reduced in both males and females. However, there appears to be no significant difference in the ability of basal stem cells isolated from individual young and old mice to form clonal tracheospheres in culture or in the ability of the epithelium to repair after damage by inhaled sulfur dioxide. Gene expression analysis by Affymetrix microarray and quantitative PCR, as well as immunohistochemistry and flow sorting studies, are consistent with low-grade chronic inflammation in the tracheas of old versus young mice and an increase in the number of immune cells. The significance of these changes for ARGL formation are not clear since several treatments that induce acute inflammation in young mice did not result in budding of the surface epithelium.
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Experimental studies have illustrated an age-associated increase in bronchoepithelial cell apoptosis, resulting in decreased cell numbers present in aged lung.
“Experimental studies have illustrated that there is an age-associated increase in bronchoepithelial cell apoptosis, resulting in decreased cell numbers present in aged lung (61).”
From Aging and Lung Disease (2020) · cites this paper as [61]
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- Authors
- Wansleeben, C., Bowie, E., Hotten, D. F., Yu, Y.-R. A., & Hogan, B. L. M.
- Affiliations
- Duke University (US)
- Corresponding author
- Hogan, Brigid L. M.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-03-27
- Volume
- 9
- Issue
- 3
- Pages
- e93496
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3968161
- OpenAlex
- W2002644888
- Cited by
- 62
- References
- 42
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 2
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Ellison Medical Foundation
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R37HL071303, HL 4R37-HL07103-21)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD040372)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- trachea, aging, mucociliary epithelium, submucosal glands, basal cells, keratin 5, p63, epithelial stem cells, epithelial repair, chronic inflammation
- MeSH terms
- Aging, Animals, Bronchi, Cell Differentiation, Cell Division, Cells, Cultured, Epithelial Cells, Female, Male, Phosphoproteins, Stem Cells, Trachea, Trans-Activators, Gene Expression, Mice, Knockout, Spheroids, Cellular, Respiratory Mucosa, Mice, Keratin-15, Myeloid Differentiation Factor 88
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