title: 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.
  
  
  CONCLUSIONS
  These data provide biologic evidence that smoking accelerates aging of the small airway epithelium.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Walters
authors.forename: Bishnu P
authors.initials: BP
authors.lastname: De
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Salit
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Buro-Auriemma
authors.forename: Timothy
authors.initials: T
authors.lastname: Wilson
authors.forename: Allison M
authors.initials: AM
authors.lastname: Rogalski
authors.forename: Lindsay
authors.initials: L
authors.lastname: Lief
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Staudt
authors.forename: Ann E
authors.initials: AE
authors.lastname: Tilley
authors.forename: Ben-Gary
authors.initials: BG
authors.lastname: Harvey
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kaner
authors.forename: Jason G
authors.initials: JG
authors.lastname: Mezey
authors.forename: Beth
authors.initials: B
authors.lastname: Ashbridge
authors.forename: Malcolm A S
authors.initials: MA
authors.lastname: Moore
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics / Q000473:pathology; D016615:Telomere / Q000235:genetics; D059506:Telomere Shortening
chemical_list: D012333:RNA, Messenger; D012906:Smoke