Cellular Senescence: The Trojan Horse in Chronic Lung Diseases

Am J Respir Cell Mol Biol. 2019 Jul;61(1):21-30. doi: 10.1165/rcmb.2018-0410TR.

Abstract

Senescence is a cell fate decision characterized by irreversible arrest of proliferation accompanied by a senescence-associated secretory phenotype. Traditionally, cellular senescence has been recognized as a beneficial physiological mechanism during development and wound healing and in tumor suppression. However, in recent years, evidence of negative consequences of cellular senescence has emerged, illuminating its role in several chronic pathologies. In this context, senescent cells persist or accumulate and have detrimental consequences. In this review, we discuss the possibility that in chronic obstructive pulmonary disease, persistent senescence impairs wound healing in the lung caused by secretion of proinflammatory senescence-associated secretory phenotype factors and exhaustion of progenitor cells. In contrast, in idiopathic pulmonary fibrosis, chronic senescence in alveolar epithelial cells exacerbates the accumulation of senescent fibroblasts together with production of extracellular matrix. We review how cellular senescence may contribute to lung disease pathology.

Keywords: chronic obstructive pulmonary disease; idiopathic pulmonary fibrosis; lung; senescence; senescence-associated secretory phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alveolar Epithelial Cells / metabolism*
  • Alveolar Epithelial Cells / pathology
  • Cellular Senescence*
  • Chronic Disease
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Humans
  • Idiopathic Pulmonary Fibrosis / metabolism*
  • Idiopathic Pulmonary Fibrosis / pathology
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Wound Healing*