Journal
RESPIRATORY INVESTIGATION
Volume 60, Issue 1, Pages 33-44Publisher
ELSEVIER
DOI: 10.1016/j.resinv.2021.09.003
Keywords
Autophagy; Chronic obstructive pulmonary disease; Lysosome; Senescence; Senotherapy
Categories
Funding
- JSPS KAKENHI [18K08158]
- Uehara memorial foundation
- Grants-in-Aid for Scientific Research [18K08158] Funding Source: KAKEN
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Chronic obstructive pulmonary disease (COPD), a lung disorder associated with aging, is primarily caused by cigarette smoke exposure. Cigarette smoke induces cellular senescence and contributes to COPD pathogenesis. Autophagy activation may be a potential therapeutic approach for COPD treatment.
Chronic obstructive pulmonary disease (COPD)1' a representative aging-related pulmo nary disorder, is mainly caused by cigarette smoke (CS) exposure. Age is one of the most important risk factors for COPD development, and increased cellular senescence in tissues and organs is a component of aging. CS exposure can induce cellular senescence, as characterized by irreversible growth arrest and aberrant cytokine secretion of the senescence-associated secretory phenotype; thus, accumulation of senescent cells is widely implicated in COPD pathogenesis. CS-induced oxidative modifications to cellular components may be causally linked to accelerated cellular senescence, especially during accumulation of damaged macromolecules. Autophagy is a conserved mechanism whereby cytoplasmic components are sent for lysosomal degradation to maintain pro teostasis. Autophagy diminishes with age, and loss of proteostasis is one of the hall- marks of aging. We have reported the involvement of insufficient autophagy in regulating CS-induced cellular senescence with respect to COPD pathogenesis. However, the role of autophagy in COPD pathogenesis can vary based on levels of cell stress and type of se lective autophagy because excessive activation of autophagy can be responsible for inducing regulated cell death. Senotherapies targeting cellular senescence may be effective COPD treatments. Autophagy activation could be a promising sonotherapeutic approach, but the optimal modality of autophagy activation should be examined in future studies. (C) 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
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