Autophagy and Cellular Senescence in Lung Diseases

Abstract

cells. The detailed molecular mechanism for regulation of autophagy and cellular senescence is complex and the role of autophagy and cellular senescence is overlap significantly. We review molecular mechanisms of autophagy and cellular senescence, and summarize the role of autophagy and cellular senescence in pulmonary disease pathogeneses. AUTOPHAGYAutophagy is a process of lysosomal self-degradation that helps maintain homeostatic balance between the synthesis, degradation and recycling of cellular proteins and organelles [1] . At the cellular level, auto-digestion takes place within lysosomes and proteasomes. Proteasomes are involved in the clearance of ubiquitin-conjugated soluble proteins, whereas autophagy delivers diverse cytoplasmic components to the lysosome, including soluble proteins, aggregateprone proteins, and organelles [2] . Autophagy is not simply machinery for amino acid supply in response to energy demand, it is an adaptive pathway of cytoprotection from cellular stresses, involving starvation, reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and microbe infection [2] . ABSTRACTAutophagy is a process of lysosomal self-degradation that helps maintain homeostatic balance between the synthesis, degradation and recycling of cellular proteins and organelles. In addition to nutrient starvation, a wide array of cellular stresses are also known to be strong inducers of autophagy, indicating that autophagy is not only simple amino acid supply machinery in response to energy demand but also a central component of the integrated stress response for cytoprotection. Since autophagy is an adaptive pathway of cytoprotection from cellular stresses, involving starvation, reactive oxygen species, endoplasmic reticulum stress, and microbe infection, it is reasonable to suggest that autophagy is closely related with aging. Indeed, autophagy diminishes with aging and accelerated aging can be attributed to reduced autophagy. Cellular senescence is also one of the cellular stress responses as well as autophagy, and considered to be one of the processes of aging. Cellular senescence has been widely implicated in disease pathogenesis in terms of not only impaired cell repopulation but also aberrant cytokine secretions of senescence associated secretory phenotype, which may exert deleterious effects on the tissue microenvironment of neighboring

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology

“…Apart from the structural cells in the airway, the innate and adaptive immune cells also play a vital role in the immunopathogenesis of CS/age-related COPD-emphysema [ 20 , 47 – 49 ]. The airways of COPD patients are populated with several types of immune cells such as macrophages, neutrophils, T-lymphocytes and dendritic cells, which collectively mediate the hyper-inflammatory state observed in COPD lungs [ 47 ].…”

Autophagy and Asthma

“…The role of autophagy in respiratory diseases is attracting increasing interest as the interface between the lungs and the environment leads to exposure to a diverse array of environmental and infectious cellular stressors. Thus, the view that the mitigation of autophagy‐mediated cellular stress plays a key regulatory role in lung pathophysiology is an attractive one . For example, a number of studies have demonstrated that autophagy may play an important role in the pathogenesis of COPD and idiopathic pulmonary fibrosis .…”

Extracellular Vesicles in Chronic Obstructive Pulmonary Disease

“…COPD shows several aging-related hallmarks [37,38]: shorter telomere length [39]; cellular senescence in epithelial cells, endothelial cells and fibroblasts [40,41]; epigenetic alterations (e.g., such as those mediated by the sirtuin family of class III histone deacetylases) [42,43]; and mitochondrial dysfunction [44,45]. Excessive reactive oxygen species (ROS), which are formed during oxygen metabolism and induced by various stresses such as cigarette smoke, evoke the occurrence of molecular damage, resulting in cell cycle arrest and the accumulation of senescent cells [46].…”