Mechanisms of Dysfunction in Senescent Pulmonary Endothelium
Open accessAbstract
Age-dependent changes in pulmonary endothelium contribute to worsened clinical outcomes in elderly individuals. Due to altered pulmonary endothelial responses, older participants have increased vulnerability to infection-related sequelae, higher prevalence of pulmonary hypertension, mitigated DNA repair mechanisms, and attenuated parenchymal healing. Aberrant signaling in pulmonary endothelium undergird these clinical processes. In this review, we provide an overview of the work that has elucidated age-related molecular derangements in pulmonary endothelial cells. In particular, we summarize studies describing mishandling of intracellular reactive oxygen species, pathological nitric oxide signaling, and deficient recruitment of endothelial stem cell precursors. We conclude with a summary of potential future avenues of investigation. The signaling pathways associated with pulmonary endothelial senescence reviewed herein suggest a number of putative therapeutic drug targets. Further elucidation of the cellular processes associated with aging in the pulmonary endothelium may provide critical insights into the rational design of therapies that may subvert or even reverse the effects of aging on a molecular level.
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Upregulation of epithelial cell surface receptors in response to chronic inflammation increases bacterial adhesion and accumulation in the aged lung and correlates with susceptibility to pneumonia.
“Upregulation of epithelial cell surface receptors in response to chronic inflammation increases bacterial adhesion and accumulation in the aged lung and correlates with susceptibility to pneumonia (62, 97).”
From Aging and Lung Disease (2020) · cites this paper as [97]
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- Authors
- Jane-Wit, D., & Chun, H. J.
- Affiliations
- Yale University (US)
- ORCID
- Chun, H. J.
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-03-01
- Volume
- 67A
- Issue
- 3
- Pages
- 236-241
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC3297765
- OpenAlex
- W2113669722
- Cited by
- 38
- References
- 47
- Citations by year
- 2025: 2 · 2024: 6 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 4
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (HL-095654, K08HL095654)
- National Institute of Allergy and Infectious Diseases (T32AI089704)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- aging, endothelial dysfunction, reactive oxygen species, nitric oxide signaling, pulmonary hypertension, DNA repair, infection susceptibility, therapeutic target
- MeSH terms
- Aging, Animals, Endothelium, Humans, Hypertension, Pulmonary, Lung, Nitric Oxide, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, Respiratory Mucosa, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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