Dataset Information

Smoking accelerates aging of the small airway epithelium.

ABSTRACT:

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.

SUBMITTER: Walters MS

PROVIDER: S-EPMC4189169 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Smoking accelerates aging of the small airway epithelium.

Walters Matthew S MS De Bishnu P BP Salit Jacqueline J Buro-Auriemma Lauren J LJ Wilson Timothy T Rogalski Allison M AM Lief Lindsay L Hackett Neil R NR Staudt Michelle R MR Tilley Ann E AE Harvey Ben-Gary BG Kaner Robert J RJ Mezey Jason G JG Ashbridge Beth B Moore Malcolm A S MA Crystal Ronald G RG

Respiratory research 20140924

<h4>Background</h4>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 heal ...[more]

PMID: 25248511

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Project description:Waterpipe (also called hookah, shisha, or narghile) smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use waterpipe smoking on DNA methylation of the small airway epithelium (SAE) and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 ± 1.7 sessions/wk) waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, p<0.05) representing 673 unique genes. Dominant pathways associated with these epigenetic changes include those linked to G-protein coupled receptor signaling, aryl hydrocarbon receptor signaling and xenobiotic metabolism signaling, all of which have been associated with cigarette smoking and lung disease. Of the genes differentially methylated, 11.3% exhibited a corresponding significant (p<0.05) change in gene expression with enrichment in pathways related to regulation of mRNA translation and protein synthesis (eIF2 signaling and regulation of eIF4 and p70S6K signaling). Overall, these data demonstrate that light-use waterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking.

Project description:Waterpipe (also called hookah, shisha, or narghile) smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use water-pipe smoking on DNA methylation of the small airway epithelium (SAE) and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 ± 1.7 sessions/wk) waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, p<0.05) representing 673 unique genes. Dominant pathways associated with these epigenetic changes include those linked to G-protein coupled receptor signaling, aryl hydrocarbon receptor signaling and xenobiotic metabolism signaling, all of which have been associated with cigarette smoking and lung disease. Of the genes differentially methylated, 11.3% exhibited a corresponding significant (p<0.05) change in gene expression with enrichment in pathways related to regulation of mRNA translation and protein synthesis (eIF2 signaling and regulation of eIF4 and p70S6K signaling). Overall, these data demonstrate that light-use waterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking. This study demonstrates that light-use waterpipe smoking in young adults is associated with a broad range of genome-wide DNA methylation-related changes of the SAE impacting a number of genes linked to pathways previously associated with cigarette smoking. Further, many of these methylation-related changes correlate with waterpipe smoking-associated changes in the SAE transcriptome. Together, these data add to the accumulating evidence that waterpipe smoking is harmful, and may lead to lung disease.

Dataset Information

Smoking accelerates aging of the small airway epithelium.

Background

Methods

Results

Conclusion

Publications

Smoking accelerates aging of the small airway epithelium.

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