Respiratory Research (May 2018)

The aging lung: tissue telomere shortening in health and disease

  • Stephanie Everaerts,
  • Elise J. Lammertyn,
  • Dries S. Martens,
  • Laurens J. De Sadeleer,
  • Karen Maes,
  • Aernoud A. van Batenburg,
  • Roel Goldschmeding,
  • Coline H. M. van Moorsel,
  • Lieven J. Dupont,
  • Wim A. Wuyts,
  • Robin Vos,
  • Ghislaine Gayan-Ramirez,
  • Naftali Kaminski,
  • James C. Hogg,
  • Wim Janssens,
  • Geert M. Verleden,
  • Tim S. Nawrot,
  • Stijn E. Verleden,
  • John E. McDonough,
  • Bart M. Vanaudenaerde

DOI
https://doi.org/10.1186/s12931-018-0794-z
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 10

Abstract

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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.

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