title: Various Mechanistic Pathways Representing the Aging Process Are Altered in COPD.
abstract: BACKGROUND
  Accelerated aging has been proposed as a pathologic mechanism of various chronic diseases, including COPD. This concept has almost exclusively been approached by analyses of individual markers. We investigated whether COPD is associated with accelerated aging using a panel of markers representing various interconnected aspects of the aging process.
  
  
  METHODS
  Lung function, leukocyte telomere length, lymphocyte gene expression of anti-aging (sirtuin 1, total klotho, and soluble klotho [Sklotho]), senescence (p16/21), and DNA repair (Ku70/80 and TERF2) proteins, and markers of systemic inflammation and oxidative stress were determined in 160 patients with COPD, 82 smoking subjects, and 38 never-smoking control subjects.
  
  
  RESULTS
  Median levels for telomere length, Sklotho, Ku70, and sirtuin 1 gene expression were lower (respectively, 4.4, 4.6, and 4.7 kbp for telomere length; 74%, 82%, and 100% for Sklotho; 88%, 92%, and 100% for Ku70 and 70%, 92%, and 100% for sirtuin 1, all P < .05) in patients compared with the smoking and never-smoking control groups. P21 gene expression was higher in patients compared with smoking control subjects. Telomere length correlated with Ku70 gene expression (r = 0.15, P = .02). After correction for age, smoking history, systemic inflammation, and oxidative stress, telomere length and p21 were the only markers that remained independently associated with lung function. In separate groups, only telomere length remained associated with lung function parameters.
  
  
  CONCLUSIONS
  Markers of the aging mechanism represent distinct molecular aspects of aging. Among them, different markers were altered in COPD, but only telomere length was consistently associated with lung function, and seems a useful marker for expressing accelerated aging in COPD.
authors.affiliation: Research and Education, CIRO, Horn, The Netherlands; Department of Respiratory Medicine, Maastricht UMC, Maastricht, The Netherlands. Electronic address: ericarutten@ciro-horn.nl.
authors.forename: Erica P A
authors.initials: EP
authors.lastname: Rutten
authors.affiliation: Department of Respiratory Medicine, Maastricht UMC, Maastricht, The Netherlands.
authors.forename: Poornima
authors.initials: P
authors.lastname: Gopal
authors.affiliation: Research and Education, CIRO, Horn, The Netherlands; Department of Respiratory Medicine, Maastricht UMC, Maastricht, The Netherlands.
authors.forename: Emiel F M
authors.initials: EF
authors.lastname: Wouters
authors.affiliation: Research and Education, CIRO, Horn, The Netherlands.
authors.forename: Frits M E
authors.initials: FM
authors.lastname: Franssen
authors.affiliation: Department of Toxicology, Maastricht UMC, Maastricht, The Netherlands.
authors.forename: Geja J
authors.initials: GJ
authors.lastname: Hageman
authors.affiliation: Research and Education, CIRO, Horn, The Netherlands.
authors.forename: Lowie E
authors.initials: LE
authors.lastname: Vanfleteren
authors.affiliation: Research and Education, CIRO, Horn, The Netherlands.
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Spruit
authors.affiliation: Department of Respiratory Medicine, Maastricht UMC, Maastricht, The Netherlands.
authors.forename: Niki L
authors.initials: NL
authors.lastname: Reynaert
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D056564:Sirtuin 1 / Q000378:metabolism; D012907:Smoking; D059505:Telomere Homeostasis / Q000502:physiology*
chemical_list: D015415:Biomarkers; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005966:Glucuronidase; D000090265:Klotho Proteins; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: COPD; inflammation; metabolism