Telomere Dysfunction and Cell Senescence in Chronic Lung Diseases: Therapeutic Potential

Pharmacol Ther. 2015 Sep;153:125-34. doi: 10.1016/j.pharmthera.2015.06.007. Epub 2015 Jun 18.

Abstract

Cellular senescence--defined as a stable cell-cycle arrest combined with stereotyped phenotypic changes--might play a causal role in various lung diseases, including chronic obstructive pulmonary disease (COPD), which is predicted to become the third leading cause of death worldwide by 2020. COPD is characterized by slowly progressive airflow obstruction and emphysema due to destruction of the lung parenchyma and is often complicated by pulmonary hypertension (PH). No curative treatment is available. Senescent cells, which accumulate with age, are increased in lungs from patients with COPD and express a robust senescence-associated secretory phenotype (SASP), which is proinflammatory. The aim of this review is to show how senescent cells can drive the lung alterations seen in COPD, which mechanisms may be involved, and whether therapeutic interventions may slow or delay the in vitro cell-senescence process and in vivo lung alterations.

Keywords: COPD; Cellular senescence; emphysema; lung disease; pulmonary hypertension.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cellular Senescence / drug effects*
  • Humans
  • Lung Diseases / drug therapy*
  • Lung Diseases / pathology*
  • Molecular Targeted Therapy / methods*
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Telomere / drug effects*
  • Telomere / metabolism
  • Telomere / pathology*
  • Telomere Homeostasis / drug effects*