Various Mechanistic Pathways Representing the Aging Process Are Altered in COPD

Chest. 2016 Jan;149(1):53-61. doi: 10.1378/chest.15-0645. Epub 2016 Jan 6.

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.

Keywords: COPD; inflammation; metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / physiology*
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Repair / physiology
  • Female
  • Glucuronidase / metabolism
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress / physiology
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Sirtuin 1 / metabolism
  • Smoking
  • Telomere Homeostasis / physiology*

Substances

  • Biomarkers
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Glucuronidase
  • klotho protein
  • SIRT1 protein, human
  • Sirtuin 1