ArticleProceedings of the National Academy of Sciences of the United States of America2015
Telomere dysfunction causes alveolar stem cell failure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers, 3 of them syntheses 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.
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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
235 citing papers in PubMed, 3 syntheses or guidelines pooled it, 328 citations in OpenAlex.
- Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease.Frontiers in immunology · 2024Pooled it
- Pooled it
- The association between leukocyte telomere length and chronic obstructive pulmonary disease is partially mediated by inflammation: a meta-analysis and population-based mediation study.BMC pulmonary medicine · 2022Pooled it
- The telomeric DNA damage response as a therapeutic target in idiopathic pulmonary fibrosis.EMBO molecular medicine · 2026Article
- Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- TRF2 couples muscle stem cell identity to regenerative repair.Science advances · 2026Article
- Telomere dysfunction and mucociliary impairment drive idiopathic pulmonary fibrosis susceptibility: insights from a Sardinian whole-exome study.BMJ open respiratory research · 2026Article
- Mapping the dialogue: Decoding alveolar stem-niche interactions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Telomere biology disorders associated with childhood interstitial lung disease.Clinical and experimental pediatrics · 2026Article
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- Ageing-associated regenerative failure in the lung: stem cell senescence and transitional cell persistence in idiopathic pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Pleuroparenchymal fibroelastosis-like findings identify an idiopathic pulmonary fibrosis subgroup with shortened telomeres and poor prognosis.ERJ open research · 2026Article
- Interstitial lung disease and the STING pathway.The Journal of clinical investigation · 2026Review
- Review
- Unlocking Alveolar Regeneration: AT2 Stem Cells, Signaling Networks, and Therapeutic Frontiers.Stem cell reviews and reports · 2026Review
- Advances in our understanding of distal progenitors in idiopathic pulmonary fibrosis: implications for novel therapeutics.The European respiratory journal · 2026Review
- Senescence intensifies bleomycin-induced injury in idiopathic pulmonary fibrosis lung epithelial cells.ERJ open research · 2026Article
- Article
- Telomere damage-mediated senescence in alveolar epithelial type II cells but not in macrophages aggravates inflammation in acute lung injury.Respiratory research · 2026Article
- Total flavonoids of litchi seed attenuates cellular senescence by inhibiting the production of SASP through p65 suppression and ameliorates pulmonary fibrosis.Acta biochimica et biophysica Sinica · 2026Article
175 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Telomere syndromes have their most common manifestation in lung disease that is recognized as idiopathic pulmonary fibrosis and emphysema. In both conditions, there is loss of alveolar integrity, but the underlying mechanisms are not known. We tested the capacity of alveolar epithelial and stromal cells from mice with short telomeres to support alveolar organoid colony formation and found that type 2 alveolar epithelial cells (AEC2s), the stem cell-containing population, were limiting. When telomere dysfunction was induced in adult AEC2s by conditional deletion of the shelterin component telomeric repeat-binding factor 2, cells survived but remained dormant and showed all the hallmarks of cellular senescence. Telomere dysfunction in AEC2s triggered an immune response, and this was associated with AEC2-derived up-regulation of cytokine signaling pathways that are known to provoke inflammation in the lung. Mice uniformly died after challenge with bleomycin, underscoring an essential role for telomere function in AEC2s for alveolar repair. Our data show that alveoloar progenitor senescence is sufficient to recapitulate the regenerative defects, inflammatory responses, and susceptibility to injury that are characteristic of telomere-mediated lung disease. They suggest alveolar stem cell failure is a driver of telomere-mediated lung disease and that efforts to reverse it may be clinically beneficial.
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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.