Smoking accelerates aging of the small airway epithelium

Respiratory Research

Ronald G Crystal¹  Malcolm A S Moore²  Beth Ashbridge²  Jason G Mezey¹  Robert J Kaner¹  Ben-Gary Harvey¹  Ann E Tilley¹  Michelle R Staudt¹  Neil R Hackett¹  Lindsay Lief¹  Allison M Rogalski¹  Timothy Wilson¹  Lauren J Buro-Auriemma¹  Jacqueline Salit¹  Bishnu P De¹  Matthew S Walters¹ 

[1] Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, New York 10065, New York, USA;Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

关键词: Smoking;    Telomere;    Small airway epithelium;    Aging;   

Others  :  1137266
DOI  :  10.1186/s12931-014-0094-1

 received in 2013-12-03, accepted in 2014-07-31,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Walters et al.; licensee BioMed Central Ltd.

【 图 表 】

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