Cited by 38Telomeres, Telomerase, and SenescenceNitric Oxide and Endothelin EffectsGenetics, Aging, and Longevity in Model Organisms

Mechanisms of Dysfunction in Senescent Pulmonary Endothelium

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Jane-Wit, D., Chun, H. J.·2012·The Journals of Gerontology Series A: Biological Sciences and Medical Sciences

Abstract

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)
Venue
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
Published
2012-03-01
Volume
67A
Issue
3
Pages
236-241
ISSN
  • 1079-5006 (ISSN-L)
  • 1758-535X
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
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

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