Accelerated ageing of the lung in COPD: new concepts

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.

Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?

“…Of these deaths, 4 million can be attributed to respiratory diseases [2]. In many of the noncommunicable diseases, including ischaemic heart disease, diabetes, Alzheimer's disease and chronic obstructive pulmonary disease (COPD), it is proposed that acceleration of the normal ageing process is involved in disease pathogenesis [3].…”

Restoration of Corticosteroid Sensitivity in Chronic Obstructive Pulmonary Disease by Inhibition of Mammalian Target of Rapamycin

“…The majority of patients are elderly, and there is a growing evidence that COPD, particularly emphysema, presents accelerated aging of the lung (2)(3)(4). Nonprogrammed aging and cellular senescence may be accelerated by oxidative stress, which is markedly increased in COPD lungs (5,6).…”

Mammalian Target of Rapamycin: A Target for (Lung) Diseases and Aging

“…Moreover, preclinical studies suggest that small molecules that modulate aging pathways might be effective in COPD (23). Consistently, mTOR signaling is also elevated, with increased oxidative stress as a likely driver (22). Given that rapamycin affects several hallmarks of aging and has a robust effect on lifespan, it may be an interesting candidate for treatment of COPD.…”

“…A disease that dramatically increases in prevalence with age, COPD has been likened to accelerated aging of the lung (22). It is associated with several hallmarks of aging, including chronic inflammation, cell senescence, reduced stem cell function, and defective autophagy and mitochondrial function.…”