Smoking accelerates aging of the small airway epithelium

Matthew S. Walters, Bishnu P. De, Jacqueline Salit, Lauren J. Buro-Auriemma, Timothy Wilson, Allison M. Rogalski, Lindsay Lief, Neil R. Hackett, Michelle R. Staudt, Ann E. Tilley, Ben Gary Harvey, Robert J. Kaner, Jason G. Mezey, Beth Ashbridge, Malcolm A.S. Moore, Ronald Crystal

Research output: Contribution to journalArticle

29 Citations (Scopus)


Background: Aging involves multiple biologically complex processes characterized by a decline in cellular homeostasis over time leading to a loss and impairment of physiological integrity and function. Specific cellular hallmarks of aging include abnormal gene expression patterns, shortened telomeres and associated biological dysfunction. Like all organs, the lung demonstrates both physiological and structural changes with age that result in a progressive decrease in lung function in healthy individuals. Cigarette smoking accelerates lung function decline over time, suggesting smoking accelerates aging of the lung. Based on this data, we hypothesized that cigarette smoking accelerates the aging of the small airway epithelium, the cells that take the initial brunt of inhaled toxins from the cigarette smoke and one of the primary sites of pathology associated with cigarette smoking. Methods: Using the sensitive molecular parameters of aging-related gene expression and telomere length, the aging process of the small airway epithelium was assessed in age matched healthy nonsmokers and healthy smokers with no physical manifestation of lung disease or abnormalities in lung function. Results: Analysis of a 73 gene aging signature demonstrated that smoking significantly dysregulates 18 aging-related genes in the small airway epithelium. In an independent cohort of male subjects, smoking significantly reduced telomere length in the small airway epithelium of smokers by 14% compared to nonsmokers. Conclusion: These data provide biologic evidence that smoking accelerates aging of the small airway epithelium.

Original languageEnglish
Article number94
JournalRespiratory Research
Issue number1
Publication statusPublished - 24 Sep 2014
Externally publishedYes



  • Aging
  • Small airway epithelium
  • Smoking
  • Telomere

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Walters, M. S., De, B. P., Salit, J., Buro-Auriemma, L. J., Wilson, T., Rogalski, A. M., Lief, L., Hackett, N. R., Staudt, M. R., Tilley, A. E., Harvey, B. G., Kaner, R. J., Mezey, J. G., Ashbridge, B., Moore, M. A. S., & Crystal, R. (2014). Smoking accelerates aging of the small airway epithelium. Respiratory Research, 15(1), [94].