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Accelerated ageing of the lung in COPD: new concepts
  1. Nicolas Mercado,
  2. Kazuhiro Ito,
  3. Peter J Barnes
  1. Airway Disease Section, National Heart & Lung Institute, Imperial College London, London, UK
  1. Correspondence to Professor Peter J Barnes, Airway Disease Section, National Heart & Lung Institute, Dovehouse St, London SW3 6LY, UK; p.j.barnes{at}imperial.ac.uk

Abstract

The rise in life expectancy worldwide has been accompanied by an increased incidence of age-related diseases, representing an enormous burden on healthcare services and society. All vital organs lose function with age, and this is well described in the lung, with a progressive decline in pulmonary function after the age of about 25 years. The lung ages, like any other organ, with progressive functional impairment and reduced capacity to respond to environmental stresses and injury. Normal physiological ageing results in enlarged alveolar spaces and loss of lung elasticity in the elderly known as ‘senile emphysema’, whereas in COPD there is destruction of the alveolar walls and fibrosis of peripheral airways. However, COPD shows striking age-associated features, such as an increase in cellular senescence, stem cell exhaustion, increased oxidative stress, alteration in the extracellular matrix and a reduction in endogenous antiageing molecules and protective pathways such as autophagy. In this review we discuss the evidence showing how oxidative stress induces accelerated ageing by upregulating the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT/mechanistic target of rapamycin signalling pathway resulting in depletion of stem cells, defective autophagy, reduced antioxidant responses and defective mitochondrial function thus generating further oxidative stress. Understanding the mechanisms of accelerated ageing in COPD may identify novel therapeutic approaches.

  • COPD Pharmacology
  • Cough/Mechanisms/Pharmacology

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