Senescence-Associated Secretory Phenotype and Its Possible Role in Chronic Obstructive Pulmonary Disease

Abstract

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.

Shelterin Telomere Protection Protein 1 Reduction Causes Telomere Attrition and Cellular Senescence via Sirtuin 1 Deacetylase in Chronic Obstructive Pulmonary Disease

“…Senescent cells initiate a myriad of damaging stress responses, including release of senescence-associated secretory phenotype (25,26) and oxidative stress (13). We show that CSE treatment for 15 days induced cellular senescence in lung fibroblasts and epithelial cells, whereas telomere length did not reveal any significant differences between the CSE and the control group.…”

Role of macrophage migration inhibitory factor in age-related lung disease

“…Additionally, both the p16-RB and p53-21 cellular senescence pathways are suppressed by MIF and the lungs of Mif-knockout mice demonstrate increased markers of both cell senescence pathways with age (123). As cellular senescence is associated with the secretion of proinflammatory cytokines, this cellular senescence associated phenotype may contribute to ongoing inflammation and air space enlargement in the lungs of patients with COPD (59,71,143,144,148). Finally, diminished VEGF and vasculogenesis have been implicated in the pathogenesis of COPD (138,147), and Mif-knockout mice show decreased VEGF signaling in the lung in response to oxidative stress (134).…”

Senescence-Associated MCP-1 Secretion Is Dependent on a Decline in BMI1 in Human Mesenchymal Stromal Cells

“…Recently, it has been reported that cellular senescence is paralleled by a striking increase in the secretion of many factors that participate in intercellular signaling, termed the senescence-associated secretory phenotype (SASP) (16,29,44). Although several groups have reported that the execution of cellular senescence involves, and often requires, the secretion of a plethora of factors, it is not immediately clear which soluble factors are major contributors to the SASP and what exact role it plays in cellular senescence (4).…”