Researchers in the United Kingdom say they’ve found the strongest evidence yet that short telomeres contribute to the cause of idiopathic pulmonary fibrosis, a deadly and incurable lung disease of mysterious origins that affects millions worldwide.

The findings of the large-scale research study, published in The Lancet Respiratory Medicine in November, could help identify new ways to prevent or treat the devastating disease. Upon diagnosis, which can take several years, the median survival for patients is three or four years.

The study linked short telomeres, the protective component at the end of DNA strands — envision the plastic bits on the ends of a shoelace — to higher risk of having IPF. The significant finding also helps to address the “idiopathic” in the disease’s name, which means its cause is unknown, a huge frustration for patients, explained Chris Scotton, senior researcher on the project.

“Short telomeres definitely seem to be causal for the development of IPF,” said Scotton, a senior lecturer in lung pathobiology and associate director of postgraduate research at the Institute of Biomedical and Clinical Science at the University of Exeter Medical School. “The shorter the telomeres, the more likely you are to be at risk of IPF.”

“If we know that short telomeres can drive or cause the development of lung fibrosis, maybe that’s something that we can intervene against in some fashion,” he continued. 

Telomeres naturally shorten with age, but various measures can give them a boost, such as diet modifications, exercise and other forms of stress reduction.

“Maybe there are also pharmacological or clinical interventions that might be possible,” Scotton added.  

With IPF, the lungs develop abnormal scar tissue that progressively reduces a person’s ability to breathe. It’s not a cancer but behaves like one, and the prognosis is “just as bad or worse,” Scotton said. “The bottom line is that IPF is an absolutely devastating condition.” 

For unclear reasons, the disease is also becoming more common. IPF has an estimated prevalence of 13 to 20 of every 100,000 people worldwide, according to the National Institutes of Health. This amounts to 3 million individuals, pharmaceutical company Boehringer Ingelheim notes. About 100,000 people in the U.S. are affected and annual diagnoses total 30,000 to 40,000, according to NIH.

In the U.K., IPF affects at least 32,000 people yet accounts for a disproportionate 1% of all deaths, or 5,300 annually.

Howard Almond, who worked with Scotton on the study, is one of those affected. Working on a patient involvement group at the university called Exeter Patients in Collaboration for pulmonary fibrosis research, or EPIC, designed to help direct the research and provide valuable perspective, Almond gathered feedback from patients and aided in drafting the manuscript to make it clearer for them.

“It’s unusual; it’s the first time in my experience as an academic researcher that I’ve ever had a patient as a co-author,” Scotton said. “But it’s a really nice thing to have done.”

Existing observations indicated that IPF patients have shorter telomeres, and clinical data has shown that much shorter telomeres are associated with a worse outcome. But it wasn’t clear whether IPF was shortening the telomeres, or the telomeres were driving the disease process.

To tease that out, researchers leveraged from UK Biobank the data of more than 1,300 patients with IPF and 13,500 with chronic obstructive pulmonary disease, or COPD, a more prevalent condition that is also associated with aging, failure to repair lungs and shorter telomeres in white blood cells. The study also included replication cohorts.

Using the complex genetic technique Mendelian randomization, which is similar to a randomized control trial but is based on genetics and eliminates confounding factors, the researchers examined DNA bases associated with controlling telomere length.

They observed a “really, really strong relationship” inferring short telomeres are causal in IPF, but saw “no evidence at all” of the same in COPD, Scotton said.

“Despite the clinical observations in both of those conditions and similar feelings about the underlying pathology,” he continued, “We only found the causal relationship in IPF.”

Scotton, who is also chairperson of the British Association for Lung Research, is now developing a clinical study to target telomere maintenance to benefit patients with lung fibrosis. The team is also interested in following up on potential use of hormone manipulation, as one of the existing drugs that could be helpful relates to hormones.

Now that they’ve established a foundation getting at the underlying pathology driving IPF, scientists have a good place to start searching for ways to slow down or stop progression of the disease.

“I don’t know if we’d ever actually make a patient better, but if we can stop them getting worse and maintain their life and quality of life, that would be good,” Scotton said. 

The study “Telomere length and risk of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease: a mendelian randomisation study,” published Nov. 13 in The Lancet Respiratory Medicine, was authored by Anna Duckworth, University of Exeter and Exeter Patients in Collaboration for PF; Michael A. Gibbons, University of Exeter and Exeter Patients in Collaboration for PF; Richard J. Allen, University of Leicester; Howard Almond, Exeter Patients in Collaboration for PF; Robin N. Beaumont, University of Exeter; Andrew R. Wood, University of Exeter; Katie Lunnon, University of Exeter; Mark A. Lindsay, University of Bath; Louise V. Wain, University of Leicester and Glenfield Hospital; Jess Tyrrell, University of Exeter; and Chris J. Scotton, University of Exeter and Exeter Patients in Collaboration for PF.