ArticleThe Journal of biological chemistry2015
Telomerase Deficiency Causes Alveolar Stem Cell Senescence-associated Low-grade Inflammation in Lungs.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 90 citations in OpenAlex.
- Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- The telomeric DNA damage response as a therapeutic target in idiopathic pulmonary fibrosis.EMBO molecular medicine · 2026Article
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- GDF11-secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Tissue Fibrosis Decoded via Cellular Senescence: Mechanisms, Treatments, and Emerging Technologies.Aging and disease · 2025Review
- Telomere attrition alters extracellular vesicles conferring adverse impacts on neuronal viability and inflammatory response.iScience · 2025Article
- Telomere function and regulation from mouse models to human ageing and disease.Nature reviews. Molecular cell biology · 2025Review
- Unveiling mechanisms of lung aging in COPD: A promising target for therapeutics development.Chinese medical journal pulmonary and critical care medicine · 2024Review
- Biomarkers of Aging and Relevant Evaluation Techniques: A Comprehensive Review.Aging and disease · 2024Review
- mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.EMBO reports · 2024Article
- Role of telomere dysfunction and immune infiltration in idiopathic pulmonary fibrosis: new insights from bioinformatics analysis.Frontiers in genetics · 2024Article
- Boosting NAD ameliorates hematopoietic impairment linked to short telomeres in vivo.GeroScience · 2023Article
- Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology.Acta neuropathologica communications · 2023Article
- Heat-KilledInternational journal of molecular sciences · 2023Article
- Mitochondrial-related microRNAs and their roles in cellular senescence.Frontiers in physiology · 2023Review
- Aging and aging-related diseases: from molecular mechanisms to interventions and treatments.Signal transduction and targeted therapy · 2022Review
- The landscape of aging.Science China. Life sciences · 2022Review
- Review
- The road-map for establishment of a prognostic molecular marker panel in glioma using liquid biopsy: current status and future directions.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Lyon IARC Polyomavirus Displays Transforming Activities in Primary Human Cells.Journal of virology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations of human telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT) are associated with a subset of lung aging diseases, but the mechanisms by which TERC and TERT participate in lung diseases remain unclear. In this report, we show that knock-out (KO) of the mouse gene Terc or Tert causes pulmonary alveolar stem cell replicative senescence, epithelial impairment, formation of alveolar sacs, and characteristic inflammatory phenotype. Deficiency in TERC or TERT causes a remarkable elevation in various proinflammatory cytokines, including IL-1, IL-6, CXCL15 (human IL-8 homolog), IL-10, TNF-α, and monocyte chemotactic protein 1 (chemokine ligand 2 (CCL2)); decrease in TGF-β1 and TGFβRI receptor in the lungs; and spillover of IL-6 and CXCL15 into the bronchoalveolar lavage fluids. In addition to increased gene expressions of α-smooth muscle actin and collagen 1α1, suggesting myofibroblast differentiation, TERC deficiency also leads to marked cellular infiltrations of a mononuclear cell population positive for the leukocyte common antigen CD45, low-affinity Fc receptor CD16/CD32, and pattern recognition receptor CD11b in the lungs. Our data demonstrate for the first time that telomerase deficiency triggers alveolar stem cell replicative senescence-associated low-grade inflammation, thereby driving pulmonary premature aging, alveolar sac formation, and fibrotic lesion.
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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.