UBC Faculty Research and Publications

The aging lung: tissue telomere shortening in health and disease Everaerts, Stephanie; Lammertyn, Elise J; Martens, Dries S; 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 S; Verleden, Stijn E; McDonough, John E; Vanaudenaerde, Bart M

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 

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