Arguing for Cellular Senescence as a Contribution to Chronic Obstructive Pulmonary Disease

Senescent cells rise in number with aging, in an evolved adaptation of developmental machinery that at least initially reduces cancer risk by removing potentially damaged cells from the cycle of division and replication. Many senescent cells are destroyed by the immune system, at least until the immune system begins its own age-related decline in earnest. More than enough senescent cells remain to cause issues, however: they export proteins that degrade surrounding tissues and promote chronic inflammation in a process known as the senescence-associated secretory phenotype (SASP). When many senescent cells are present in tissue SASP becomes a serious issue, causing enough harm and inflammation to promote the development of cancer and many other serious age-related conditions. This is more readily apparent and measured where external factors such as smoking are at work to provide the sort of toxicity that strongly promotes cellular senescence:

Chronic obstructive pulmonary disease (COPD) is a major disease of the lungs. It primarily occurs after a prolonged period of cigarette smoking. Chronic inflammation of airways and the alveolar space as well as lung tissue destruction are the hallmarks of COPD. Recently it has been shown that cellular senescence might play a role in the pathogenesis of COPD.

Cellular senescence comprises signal transduction program, leading to irreversible cell cycle arrest. The growth arrest in senescence can be triggered by many different mechanisms, including DNA damage and its recognition by cellular sensors, leading to the activation of cell cycle checkpoint responses and activation of DNA repair machinery.

Senescence can be induced by several genotoxic factors apart from telomere attrition. When senescence induction is based on DNA damage, senescent cells display a unique phenotype, which has been termed "senescence-associated secretory phenotype" (SASP). SASP may be an important driver of chronic inflammation and therefore may be part of a vicious cycle of inflammation, DNA damage, and senescence. This research perspective aims to showcase cellular senescence with relevance to COPD and the striking similarities between the mediators and secretory phenotype in COPD and SASP.


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