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Title: | The aging lung: tissue telomere shortening in health and disease | Authors: | Everaerts, Stephanie Lammertyn, Elise J. MARTENS, Dries De Sadeleer, Laurens J. Maes, Karen van Batenburg, Aernoud A. Goldschmeding, Roel van Moorsel, Coline H. M. Dupont, Lieven J. Wuyts, Wim A. Vos, Robin Gayan-Ramirez, Ghislaine Kaminski, Naftali Hogg, James C. Janssens, Wim Verleden, Geert M. NAWROT, Tim Verleden, Stijn E. McDonough, John E. Vanaudenaerde, Bart M. V. |
Issue Date: | 2018 | Source: | RESPIRATORY RESEARCH, 19 (Art N° 95) | Abstract: | Background: Telomere shortening has been associated with several lung diseases. However, telomere length is generally measured in peripheral blood leucocytes rather than in lung tissue, where disease occurs. Consequently, telomere dynamics have not been established for the normal human lung nor for diseased lung tissue. We hypothesized an age- and disease-dependent shortening of lung tissue telomeres. Methods: At time of (re-)transplantation or autopsy, 70 explant lungs were collected: from unused donors (normal, n = 13) and patients with cystic fibrosis (CF, n = 12), chronic obstructive pulmonary disease (COPD, n = 11), chronic hypersensitivity pneumonitis (cHP, n = 9), bronchiolitis obliterans syndrome (BOS) after prior transplantation (n = 11) and restrictive allograft syndrome (RAS) after prior transplantation (n = 14). Lungs were inflated, frozen and then scanned using CT. Four tissue cores from distinct lung regions were sampled for analysis. Disease severity was evaluated using CT and micro CT imaging. DNA was extracted from the samples and average relative telomere length (RTL) was determined using real-time qPCR. Results: The normal lungs showed a decrease in RTL with age (p < 0.0001). Of the diseased lungs, only BOS and RAS showed significant RTL decrease with increasing lung age (p = 0.0220 and p = 0.0272 respectively). Furthermore, we found that RTL showed considerable variability between samples within both normal and diseased lungs. cHP, BOS and RAS lungs had significant shorter RTL in comparison with normal lungs, after adjustment for lung age, sex and BMI (p < 0.0001, p = 0.0051 and p = 0.0301 respectively). When investigating the relation between RTL and regional disease severity in CF, cHP and RAS, no association was found. Conclusion: These results show a progressive decline in telomere length with age in normal, BOS and RAS lungs. cHP, BOS and RAS lungs demonstrated shorter RTL compared to normal lungs. Lung tissue RTL does not associate with regional disease severity within the lung. Therefore, tissue RTL does not seem to fully reflect peripheral blood telomere length. | Notes: | Everaerts, S (reprint author), Katholieke Univ Leuven, Lab Resp Dis, Dept Chron Dis Metab & Aging CHROMETA, O&NI, Herestr 49,Box 706, B-3000 Leuven, Belgium. stephanie.everaerts@kuleuve.be | Keywords: | cystic fibrosis; chronic obstructive pulmonary disease; chronic hypersensitivity pneumonitis; chronic lung allograft dysfunction; BOS; RAS; cellular senescence; telomere length | Document URI: | http://hdl.handle.net/1942/26131 | e-ISSN: | 1465-993X | DOI: | 10.1186/s12931-018-0794-z | ISI #: | 000432708200002 | Rights: | © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2019 |
Appears in Collections: | Research publications |
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EveraertsMartensLung2018.pdf | Published version | 1.69 MB | Adobe PDF | View/Open |
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