Chronic obstructive pulmonary disease (COPD) is characterized by progressively reduced airflow within the lungs, making it difficult to breath. During normal breathing, air sacs (alveoli) (which are elastic) fill up with air and oxygen passes through the air sac walls into the blood. With COPD the air sacs can lose elasticity, the walls between air sacs are destroyed, the walls become thick and inflamed and the airways make more mucus than normal leading to clogging. All these changes contribute to reduced airflow in COPD.
COPD is predominately associated with tobacco smoking and previous studies investigating the pathophysiology of emphysema have demonstrated that cigarette smoke can cause cells to enter cellular senescence (Tsuji et al, 2004, Nyunoya et al 2006). As such, a number of studies have investigated the role of cellular senescence in the development and progression of COPD. Cigarette smoke may trigger cells to senesce directly due to DNA damage or indirectly (if apoptosis is occurring) through increasing cell turnover leading to accelerated telomere shortening.
Senescent cells secrete pro-inflammatory cytokines, growth factors and proteases (most likely for immune clearance) that can cause tissue damage, leading to loss of function of the tissue in which they reside. In the case off COPD the secretion of proteases by senescent cells could result in loss of elasticity of air sacs and destruction of air sac walls. The secretion of cytokines and chemokines by senescent cells would lead to persistent inflammation.
Tsuji et al (2009) has shown that lung tissue of COPD patients contained higher percentages of senescent alveolar cells displaying a pro-inflammatory phenotype compared with tissue from asymptomatic smokers and non-smokers. Noureddine et al (2011) has demonstrated that pulmonary artery smooth muscle cell (PA-SMC) senescence is an important contributor in the process of pulmonary vessel remodeling in COPD patients. Senescent PA-SMC were shown to stimulate cell growth and migration of normal PA-SMC through the release of paracrine soluble and insoluble factors. Dogauassat et al (2011) have shown that lung fibroblasts in smokers and ex-smokers with moderate COPD display a senescent phenotype. This study suggests that even after stopping smoking, the persistence of senescent cells may still contribute to COPD. Amsellem et al (2011) have recently showed that premature senescence in pulmonary vascular endothelial cells may contribute to inflammation in COPD.
Research also suggests that patients with COPD have a two to six times more chance of developing lung cancer compared with people of normal lung function (COPD Foundation). It could be speculated that the presence of senescent cells in COPD patients may increase the chances of lung cancer. It has been shown that the secretory phenotype of senescent cells can play a role in cancer development by stimulating growth and angiogenic activity of pre-malignant cells (reviewed in Campisi and d'Adda di Fagagna, 2007). Additionally, stochastic epigenetic/genetic alterations within senescent cells may allow them to escape the senescence growth arrest, thus becoming cancerous.
Tsuji T, Aoshiba K, Nagai A. Alveolar cell senescence exacerbates pulmonary inflammation in patients with chronic obstructive pulmonary disease. Respiration. 2010;80(1):59-70. Epub 2009 Dec 17.