{"title":"Senescence-associated microvascular endothelial dysfunction: A focus on the blood-brain and blood-retinal barriers","authors":"","doi":"10.1016/j.arr.2024.102446","DOIUrl":null,"url":null,"abstract":"<div><p>The blood-brain barrier (BBB) and blood-retinal barrier (BRB) constitute critical physiochemical interfaces, precisely orchestrating the bidirectional communication between the brain/retina and blood. Increased permeability or leakage of these barriers has been demonstrably linked to age-related vascular and parenchymal damage. While it has been suggested that the gradual aging process may coincide with disruptions in these barriers, this phenomenon is significantly exacerbated in individuals with age-related neurodegenerative disorders (ARND). This review focuses on the microvascular endothelium, a key constituent of BBB and BRB, highlighting the impact of endothelial senescence on barrier dysfunction and exploring recent discoveries regarding core pathways implicated in its breakdown. Subsequently, we address the \"vascular senescence hypothesis\" for ARND, with a particular emphasis on Alzheimer's disease and age-related macular degeneration, centered on endothelial senescence. Finally, we discuss potential senotherapeutic strategies targeting barrier dysfunction.</p></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":null,"pages":null},"PeriodicalIF":12.5000,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ageing Research Reviews","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1568163724002642","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The blood-brain barrier (BBB) and blood-retinal barrier (BRB) constitute critical physiochemical interfaces, precisely orchestrating the bidirectional communication between the brain/retina and blood. Increased permeability or leakage of these barriers has been demonstrably linked to age-related vascular and parenchymal damage. While it has been suggested that the gradual aging process may coincide with disruptions in these barriers, this phenomenon is significantly exacerbated in individuals with age-related neurodegenerative disorders (ARND). This review focuses on the microvascular endothelium, a key constituent of BBB and BRB, highlighting the impact of endothelial senescence on barrier dysfunction and exploring recent discoveries regarding core pathways implicated in its breakdown. Subsequently, we address the "vascular senescence hypothesis" for ARND, with a particular emphasis on Alzheimer's disease and age-related macular degeneration, centered on endothelial senescence. Finally, we discuss potential senotherapeutic strategies targeting barrier dysfunction.
期刊介绍：
With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends.
ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research.
The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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