CFTR expression decreases with age in several airway cell types

Timothy E Corcoran1,2,3, Matthew J Broerman4, Corrine R Kliment4

  • 1Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh, UPMC MUH NW628, 3459 Fifth Ave, Pittsburgh, PA, 15213, USA. tec23@pitt.edu.

Scientific Reports
|November 21, 2024
PubMed

Insights

Lung defense, mucociliary clearance (MC), declines with age. This study finds that Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene expression decreases in aging lung cells, potentially explaining reduced MC and increased infection risk.

Area of Science:

  • Pulmonary Medicine
  • Molecular Biology
  • Aging Research

Background:

  • The mucociliary clearance (MC) system is crucial for lung defense against pathogens.
  • MC efficiency relies on ciliary function and airway surface liquid (ASL) hydration.
  • Age-related decline in MC is linked to increased pulmonary infection rates in older adults.

Purpose of the Study:

  • To investigate age-related changes in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene expression in the human lung.
  • To determine if reduced CFTR expression contributes to the age-associated decline in MC.

Main Methods:

  • Utilized bulk (GTEx) and single-cell (CELLxGENE) lung sequencing data.
  • Analyzed CFTR expression patterns across different lung cell types in relation to age.

Main Results:

  • Both bulk and single-cell analyses revealed a significant decrease in CFTR expression with increasing age.
  • CFTR expression declined in goblet, club, and basal cells, which are major sources of CFTR.
  • No significant age-related decrease in CFTR expression was observed in ciliated airway cells.

Conclusions:

  • Decreased CFTR expression in aging lung secretory and basal cells may lead to ASL dehydration.
  • This dehydration can impair MC, contributing to the higher susceptibility to lung infections in the elderly.
  • Findings highlight a potential molecular mechanism underlying age-related pulmonary defense deficits.