Cellular senescence in the lung across the age spectrum

Pavan Parikh, Sarah Wicher, Karl Khandalavala, Christina M. Pabelick, Rodney D. Britt, Y. S. Prakash

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations

Abstract

Cellular senescence results in cell cycle arrest with secretion of cytokines, chemokines, growth factors, and remodeling proteins (senescence-associated secretory phenotype; SASP) that have autocrine and paracrine effects on the tissue microenvironment. SASP can promote remodeling, inflammation, infectious susceptibility, angiogenesis, and proliferation, while hindering tissue repair and regeneration. While the role of senescence and the contributions of senescent cells are increasingly recognized in the context of aging and a variety of disease states, relatively less is known regarding the portfolio and influences of senescent cells in normal lung growth and aging per se or in the induction or progression of lung diseases across the age spectrum such as bronchopulmonary dysplasia, asthma, chronic obstructive pulmonary disease, or pulmonary fibrosis. In this review, we introduce concepts of cellular senescence, the mechanisms involved in the induction of senescence, and the SASP portfolio that are relevant to lung cells, presenting the potential contribution of senescent cells and SASP to inflammation, hypercontractility, and remodeling/fibrosis: aspects critical to a range of lung diseases. The potential to blunt lung disease by targeting senescent cells using a novel class of drugs (senolytics) is discussed. Potential areas for future research on cellular senescence in the lung are identified.

Original languageEnglish (US)
Pages (from-to)L826-L842
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume316
Issue number5
DOIs
StatePublished - May 2019

Keywords

  • Aging
  • Airway
  • Alveoli
  • Bronchi
  • Senolytic

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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