For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
21
views
32
references
 Top references
cited by
73
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      549
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Cellular senescence-like features of lung fibroblasts derived from idiopathic pulmonary fibrosis patients

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Idiopathic pulmonary fibrosis (IPF) is an age-related fatal disease with unknown etiology and no effective treatment. In this study, we show that primary cultures of fibroblasts derived from lung biopsies of IPF patients exhibited (i) accelerated replicative cellular senescence (CS); (ii) high resistance to oxidative-stress-induced cytotoxicity or CS; (iii) a CS-like morphology (even at the proliferative phase); and (iv) rapid accumulation of senescent cells expressing the myofibroblast marker α-SMA. Our findings suggest that CS could serve as a bridge connecting lung aging and its quite frequent outcome -- pulmonary fibrosis, and be an important player in the disease progression. Consequently, targeting senescent cells offers the potential of being a promising therapeutic approach.

          Related collections

          Most cited references32

          • Record: found
          • Abstract: found
          • Article: not found

          Telomerase mutations in families with idiopathic pulmonary fibrosis.

          Mary Armanios, Julian J L Chen, Joy Cogan … (2007)
          Idiopathic pulmonary fibrosis is progressive and often fatal; causes of familial clustering of the disease are unknown. Germ-line mutations in the genes hTERT and hTR, encoding telomerase reverse transcriptase and telomerase RNA, respectively, cause autosomal dominant dyskeratosis congenita, a rare hereditary disorder associated with premature death from aplastic anemia and pulmonary fibrosis. To test the hypothesis that familial idiopathic pulmonary fibrosis may be caused by short telomeres, we screened 73 probands from the Vanderbilt Familial Pulmonary Fibrosis Registry for mutations in hTERT and hTR. Six probands (8%) had heterozygous mutations in hTERT or hTR; mutant telomerase resulted in short telomeres. Asymptomatic subjects with mutant telomerase also had short telomeres, suggesting that they may be at risk for the disease. We did not identify any of the classic features of dyskeratosis congenita in five of the six families. Mutations in the genes encoding telomerase components can appear as familial idiopathic pulmonary fibrosis. Our findings support the idea that pathways leading to telomere shortening are involved in the pathogenesis of this disease. Copyright 2007 Massachusetts Medical Society.
          Article 0 comments Cited 339 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Short telomeres are a risk factor for idiopathic pulmonary fibrosis.

            Jonathan Alder, Julian J L Chen, Lisa H. Lancaster … (2008)
            Idiopathic interstitial pneumonias (IIPs) have a progressive and often fatal course, and their enigmatic etiology has complicated approaches to effective therapies. Idiopathic pulmonary fibrosis (IPF) is the most common of IIPs and shares with IIPs an increased incidence with age and unexplained scarring in the lung. Short telomeres limit tissue renewal capacity in the lung and germ-line mutations in telomerase components, hTERT and hTR, underlie inheritance in a subset of families with IPF. To examine the hypothesis that short telomeres contribute to disease risk in sporadic IIPs, we recruited patients who have no family history and examined telomere length in leukocytes and in alveolar cells. To screen for mutations, we sequenced hTERT and hTR. We also reviewed the cases for features of a telomere syndrome. IIP patients had shorter leukocyte telomeres than age-matched controls (P < 0.0001). In a subset (10%), IIP patients had telomere lengths below the first percentile for their age. Similar to familial cases with mutations, IPF patients had short telomeres in alveolar epithelial cells (P < 0.0001). Although telomerase mutations were rare, detected in 1 of 100 patients, we identified a cluster of individuals (3%) with IPF and cryptogenic liver cirrhosis, another feature of a telomere syndrome. Short telomeres are thus a signature in IIPs and likely play a role in their age-related onset. The clustering of cryptogenic liver cirrhosis with IPF suggests that the telomere shortening we identify has consequences and can contribute to what appears clinically as idiopathic progressive organ failure in the lung and the liver.
            Article 0 comments Cited 231 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Telomere shortening in familial and sporadic pulmonary fibrosis.

              Jennifer T Cronkhite, Chao Xing, Ganesh Raghu … (2008)
              Heterozygous mutations in the coding regions of the telomerase genes, TERT and TERC, have been found in familial and sporadic cases of idiopathic interstitial pneumonia. All affected patients with mutations have short telomeres. To test whether telomere shortening is a frequent mechanism underlying pulmonary fibrosis, we have characterized telomere lengths in subjects with familial or sporadic disease who do not have coding mutations in TERT or TERC. Using a modified Southern blot assay, the telomerase restriction fragment length method, and a quantitative polymerase chain reaction assay we have measured telomere lengths of genomic DNA isolated from circulating leukocytes from normal control subjects and subjects with pulmonary fibrosis. All affected patients with telomerase mutations, including case subjects heterozygous for newly reported mutations in TERT, have short telomere lengths. A significantly higher proportion of probands with familial pulmonary fibrosis (24%) and sporadic case subjects (23%) in which no coding mutation in TERT or TERC was found had telomere lengths less than the 10th percentile when compared with control subjects (P = 2.6 x 10(-8)). Pulmonary fibrosis affectation status was significantly associated with telomerase restriction fragment lengths, even after controlling for age, sex, and ethnicity (P = 6.1 x 10(-11)). Overall, 25% of sporadic cases and 37% of familial cases of pulmonary fibrosis had telomere lengths less than the 10th percentile. A significant fraction of individuals with pulmonary fibrosis have short telomere lengths that cannot be explained by coding mutations in telomerase. Telomere shortening of circulating leukocytes may be a marker for an increased predisposition toward the development of this age-associated disease.
              Article 0 comments Cited 153 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Aging (Albany NY)
                Journal ID (iso-abbrev): Aging (Albany NY)
                Journal ID (publisher-id): ImpactJ
                Title: Aging (Albany NY)
                Publisher: Impact Journals LLC
                ISSN (Electronic): 1945-4589
                Publication date Collection: September 2015
                Publication date (Electronic): 22 September 2015
                Volume: 7
                Issue: 9
                Pages: 664-672
                Affiliations
                1 The Shraga Segal Department of Microbiology, Immunology and Genetics, Center for Multidisciplinary Research on Aging, Ben-Gurion University of the Negev, POB 653, Beer Sheva 84105, Israel
                2 Flow Cytometry Unit, Department of Biological services, Weizmann Institute of Science, Rehovot 76100, Israel
                3 Judea Regional Research & Development Center, Carmel 90404, Israel
                4 Division of Pulmonary Medicine, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
                Author notes
                Correspondence to: Vadim Fraifeld, MD/PhD; vadim.fraifeld@ 123456gmail.com
                Article
                DOI: 10.18632/aging.100807
                PMC ID: 4600624
                PubMed ID: 26399448
                SO-VID: 5ac700e1-215d-4bb5-96f0-272e6c2dac72
                Copyright © Copyright: © 2015 Yanai et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 9 August 2015
                Date accepted : 12 September 2015
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Cell biology
                Keywords: cellular senescence,idiopathic pulmonary fibrosis,fibroblasts,myofibroblasts,aging
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: cellular senescence, idiopathic pulmonary fibrosis, fibroblasts, myofibroblasts, aging

                Comments

                Comment on this article

                scite_

                Similar content549

                See all similar

                Cited by70

                See all cited by

                Most referenced authors631

                See all reference authors