Senescence hypothesis for the pathogenetic mechanism of chronic obstructive pulmonary disease

K Aoshiba, A Nagai - Proceedings of the American Thoracic Society, 2009 - atsjournals.org
K Aoshiba, A Nagai
Proceedings of the American Thoracic Society, 2009atsjournals.org
We report herein that pulmonary emphysematous lesions appear to be a dynamic
phenomenon that involves not only the gradual loss of alveolar structure but also apoptosis,
cellular proliferation, and cellular senescence. Cellular proliferation compensates for
increased alveolar cell apoptosis in patients with chronic obstructive pulmonary disease
(COPD). However, smoking, age, and the increased cell cycle turnover that compensates for
apoptosis accelerate alveolar cell senescence, thereby halting cellular proliferation and …
We report herein that pulmonary emphysematous lesions appear to be a dynamic phenomenon that involves not only the gradual loss of alveolar structure but also apoptosis, cellular proliferation, and cellular senescence. Cellular proliferation compensates for increased alveolar cell apoptosis in patients with chronic obstructive pulmonary disease (COPD). However, smoking, age, and the increased cell cycle turnover that compensates for apoptosis accelerate alveolar cell senescence, thereby halting cellular proliferation and tipping the balance toward apoptosis, which, in turn, promotes the formation of emphysematous lesions. As a result, alveolar cells disappear and the emphysematous lesions progress. At the same time, cellular senescence is believed to induce inflammation. More specifically, senescent alveolar cells induce inflammation by producing various inflammatory cytokines in tissue. Lymphocytes and Clara cells may also age more rapidly in the lungs of patients with COPD. Lymphocyte senescence may induce an autoimmune reaction and increase susceptibility to infection, and Clara cell senescence may impair airway regeneration as well as sustain airway inflammation. Thus, cellular senescence may be involved in arrested tissue repair, chronic inflammation, and increased susceptibility to infection, which are the typical features of COPD.
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