Emerging role of cellular senescence in normal lung development and perinatal lung injury  

作　　者：Phyllis A.Dennery Hongwei Yao 

机构地区：[1]Department of Molecular Biology,Cell Biology&Biochemistry,Division of Biology and Medicine,Brown University,Providence,RI 02912,USA [2]Department of Pediatrics,Warren Alpert Medical School of Brown University,Providence,RI 02903,USA

出　　处：《Chinese Medical Journal Pulmonary and Critical Care Medicine》2024年第1期10-16,共7页呼吸与危重症医学（英文）

基　　金：supported by an NIH R01 R01HL166327;Institutional Development Award(IDeA)from the NIGMS of NIH un-der grant No.P20GM103652;the Rhode Island Foundation grant No.14699_20231340(HY),and the Warren Alpert Foundation of Brown University(PAD).

摘　　要：Cellular senescence is a status of irreversible growth arrest,which can be triggered by the p53/p21cip1 and p16INK4/Rb pathways via intrinsic and external factors.Senescent cells are typically enlarged and flattened,and characterized by numerous molecular features.The latter consists of increased surfaceome,increased resid-ual lysosomal activity at pH 6.0(manifested by increased activity of senescence-associated beta-galactosidase[SA-𝛽-gal]),senescence-associated mitochondrial dysfunction,cytoplasmic chromatin fragment,nuclear lamin b1 exclusion,telomere-associated foci,and the senescence-associated secretory phenotype.These features vary depending on the stressor leading to senescence and the type of senescence.Cellular senescence plays pivotal roles in organismal aging and in the pathogenesis of aging-related diseases.Interestingly,senescence can also both promote and inhibit wound healing processes.We recently report that senescence as a programmed pro-cess contributes to normal lung development.Lung senescence is also observed in Down Syndrome,as well as in premature infants with bronchopulmonary dysplasia and in a hyperoxia-induced rodent model of this disease.Furthermore,this senescence results in neonatal lung injury.In this review,we briefly discuss the molecular features of senescence.We then focus on the emerging role of senescence in normal lung development and in the pathogenesis of bronchopulmonary dysplasia as well as putative signaling pathways driving senescence.Finally,we discuss potential therapeutic approaches targeting senescent cells to prevent perinatal lung diseases.

关 键 词：SENESCENCE Normal lung development Bronchopulmonary dysplasia Down syndrome Senolytics 

分 类 号：R563[医药卫生—呼吸系统]