Telomeres in Interstitial Lung Disease: The Short and the Long of It

Ann Am Thorac Soc. 2019 Feb;16(2):175-181. doi: 10.1513/AnnalsATS.201808-508CME.


Telomeres are repetitive nucleotide sequences that cap linear chromosomes, thereby limiting progressive chromosomal shortening during cell replication. In conjunction with environmental factors, common single-nucleotide polymorphisms and rare and ultra-rare telomere-related mutations are associated with accelerated telomere shortening resulting in organ dysfunction, including interstitial lung disease (ILD). The most common telomere-related mutation-associated ILD is idiopathic pulmonary fibrosis (IPF). Up to one-third of individuals with familial IPF have shortened telomeres and/or carry a telomere-related mutation, and 1 in 10 individuals with sporadic IPF have telomere-related mutations. Regardless of ILD phenotype, individuals with short telomeres and/or known telomere-related mutations have more rapid disease progression and shorter lung transplant-free survival. Management should include initiation of antifibrotic agents for those with an IPF phenotype and early referral to a transplant center. Patients with ILD being considered for transplant should be screened for short telomeres if there is a significant family history of pulmonary fibrosis or evidence of extrapulmonary organ dysfunction associated with a short telomere syndrome. Post-transplant management of recipients with telomere-related mutations should include careful adjustment of immunosuppression regimens on the basis of bone marrow reserve. Data on the impact of shortened telomeres on post-transplant outcomes, however, remain mixed.

Keywords: idiopathic pulmonary fibrosis; interstitial lung disease; lung transplantation; telomere length; telomeres.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Idiopathic Pulmonary Fibrosis / genetics*
  • Idiopathic Pulmonary Fibrosis / therapy
  • Lung Diseases, Interstitial / genetics*
  • Lung Diseases, Interstitial / therapy
  • Lung Transplantation
  • Mutation
  • Telomerase / genetics*
  • Telomere / genetics*
  • Telomere Shortening


  • Telomerase