A recent study has provided more insight into the molecular processes that might be involved in the pathological changes that take place in the lungs of patients with idiopathic pulmonary fibrosis (IPF).
In the study, “A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis,” published in the journal Respiratory Research, researchers aimed to study the association between the length of telomeres and structural changes in IPF lungs.
Telomeres are structures present at the ends of chromosomes. They stabilize chromosomes and protect them against damage. But they also shorten each time the cell divides. As a result, their length is associated with age, and once they reach a certain limit, a so-called DNA-damage response is triggered within cells resulting in cell death.
Several studies have reported the presence of shortened telomeres in IPF patients, with some associating it with decreased survival. None, however, have focused on the role of telomere length and DNA damage within the lungs and its effect on disease severity.
The team used 10 lungs from IPF patients who had undergone a lung transplant, and six healthy control lungs.
Tissue structure was assessed in all lungs using microCT scanning. Researchers also analyzed telomere length and the extent of DNA damage (using the DNA damage marker γ-H2A.X) within the lungs. Statistical tests were then performed to measure the association between telomere length and DNA damage in IPF and its effects on disease severity.
Results showed that in IPF lungs, there was an average 27% reduction in telomere length and three times more DNA damage than in controls.
The same trend was observed regarding markers of fibrosis and the values of total collagen — a structural protein produced in excess in fibrotic processes.
On closer examination, researchers found that telomere length was not associated with the extent of disease severity, while DNA damage was linked to increased disease severity.
“Telomere length and chromosomal damage are involved in IPF with regional variation in telomere length and chromosomal damage associated with pathological changes in tissue,” the researchers wrote.
“Chromosomal damage, measured by γ-H2A.X staining, was associated with parenchymal collapse but not fibrosis suggesting a role for this process in the early stages of IPF progression,” they said.