Unveiling mechanisms of lung aging in COPD: A promising target for therapeutics development  

作　　者：Justine V.Devulder 

机构地区：[1]National Heart and Lung Institute,Imperial College London,London SW36LY,UK

出　　处：《Chinese Medical Journal Pulmonary and Critical Care Medicine》2024年第3期133-141,共9页呼吸与危重症医学（英文）

摘　　要：Chronic obstructive pulmonary disease(COPD)is a chronic inflammatory lung disease characterized by airflow limitation and changes in airway structures that can lead to chronic bronchitis,small airway diseases,and emphysema.COPD is the 3rd leading cause of death worldwide and despite current research,there are no curative disease treatments for COPD.As the prevalence of COPD is higher in people over 60 years old than in younger age groups,COPD is considered a condition of accelerated lung aging.Natural lung aging is associated with molecular,cellular,and physiological changes that cause alteration in lung structure,in lung function and regeneration,and decreased immune system response that could lead to lung disease like COPD.Mechanisms of accelerated lung aging are complex and composed by increased oxidative stress induced by exposure to cigarette smoke,by chronic inflammatory processes,and increased number of senescent cells within the airways.Cellular senescence is the cessation of cell division after a finite number of proliferation cycles or in response to cell stressors,such as oxidative stress.Senescent cells show activation of the cell cycle regulators p21CIP1(cyclin-dependent kinase inhibitor-1),p16INK4(cyclin-dependent kinase inhibitor-2A),and p53(cellular tumor antigen p53)that lead to cell cycle arrest.Senescent cells exhibit a change in their phenotype and their metabolic activity,along with the production of proinflammatory proteins collectively known as senescence-associated secretory phenotype(SASP).This review aims to describe recent developments in our understanding of aging mechanisms and how the acceleration of lung aging participates in COPD pathophysiology and comorbidities.Understanding and targeting aging mechanisms may result in the development of new therapeutics that could be effective for COPD and also for other age-related diseases.

关 键 词：Chronic obstructive pulmonary disease Aging Cellular senescence Senescence-associated secretory phenotype MICRORNAS 

分 类 号：R563[医药卫生—呼吸系统]