ArticleAmerican journal of physiology. Lung cellular and molecular physiology2018
Oxidative stress associated with aging activates protein kinase Cε, leading to cilia slowing.
Article in American journal of physiology. Lung cellular and molecular physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Advances in Molecular Research of Tracheobronchial Tree Aging: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Bronchiectasis in Older Adults: Distinctive Epidemiology, Etiology, Diagnosis, and Clinical Evolution Compared with Younger Populations.Drugs & aging · 2026Review
- Pharmacological regulation of airway ciliary motility: endogenous mediators, pharmaceutical agents, and natural compounds with a focus on ginsenoside Rd.Journal of natural medicines · 2026Review
- Ciliary-Mediated Mechanotransduction in Skeletal Development and Diseases.Results and problems in cell differentiation · 2026Review
- Klotho Regulates Club Cell Senescence and Differentiation in Chronic Obstructive Pulmonary Disease.Cell proliferation · 2025Article
- The alcohol exposome.Alcohol (Fayetteville, N.Y.) · 2025Review
- Modulation of pulmonary immune functions by theFrontiers in immunology · 2025Review
- CFTR expression decreases with age in several airway cell types.Scientific reports · 2024Article
- Biomarkers of aging.Science China. Life sciences · 2023Review
- Epidemiology and Clinical Presentation of COVID-19 in Older Adults.Infectious disease clinics of North America · 2023Review
- Intersection of Inflammation and Senescence in the Aging Lung Stem Cell Niche.Frontiers in cell and developmental biology · 2022Review
- Immunosenescence: A Critical Factor Associated With Organ Injury After Sepsis.Frontiers in immunology · 2022Review
- Aging Diminishes Mucociliary Clearance of the Lung.Advances in geriatric medicine and research · 2022Article
- Modulation of the long non-coding RNA Mir155hg by high, but not moderate, hydrostatic pressure in cartilage precursor cells.PloS one · 2022Article
- Malondialdehyde-Acetaldehyde Adduct Formation Decreases Immunoglobulin A Transport across Airway Epithelium in Smokers Who Abuse Alcohol.The American journal of pathology · 2021Article
- Review
- Alcohol use disorder: A pre-existing condition for COVID-19?Alcohol (Fayetteville, N.Y.) · 2021Review
- First contact: the role of respiratory cilia in host-pathogen interactions in the airways.American journal of physiology. Lung cellular and molecular physiology · 2020Review
- Mitochondrial dysfunction in lung ageing and disease.European respiratory review : an official journal of the European Respiratory Society · 2020Review
- Senotherapeutics: Targeting senescence in idiopathic pulmonary fibrosis.Seminars in cell & developmental biology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Older people are four times more likely to develop pneumonia than younger people. As we age, many components of pulmonary innate immunity are impaired, including slowing of mucociliary clearance. Ciliary beat frequency (CBF) is a major determinant of mucociliary clearance, and it slows as we age. We hypothesized that CBF is slowed in aging because of increased oxidative stress, which activates PKCε signaling. We pharmacologically inhibited PKCε in ex vivo mouse models of aging. We measured a slowing of CBF with aging that was reversed with inhibition using the novel PKC inhibitor, Ro-31-8220, as well as the PKCε inhibitor, PKCe141. Inhibition of PKCε using siRNA in mouse trachea also returned CBF to normal. In addition, antioxidants decrease PKCε activity and speed cilia. We also aged wild-type and PKCε KO mice and measured CBF. The PKCε KO mice were spared from the CBF slowing of aging. Using human airway epithelial cells from younger and older donors at air-liquid interface (ALI), we inhibited PKCε with siRNA. We measured a slowing of CBF with aging that was reversed with siRNA inhibition of PKCε. In addition, we measured bead clearance speeds in human ALI, which demonstrated a decrease in bead velocity with aging and a return to baseline after inhibition of PKCε. In summary, in human and mouse models, aging is associated with increased oxidant stress, which activates PKCε and slows CBF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.