Aging-Driven Blood–Brain Barrier Dysfunction and Its Impact on CNS Cancer Susceptibility: A Comprehensive Narrative Review

Aging and cancer Pub Date : 2025-04-23 DOI:10.1002/aac2.70002

Quang La, Aiman Baloch, David F. Lo

{"title":"Aging-Driven Blood–Brain Barrier Dysfunction and Its Impact on CNS Cancer Susceptibility: A Comprehensive Narrative Review","authors":"Quang La, Aiman Baloch, David F. Lo","doi":"10.1002/aac2.70002","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Aging significantly affects the structural and functional integrity of the blood–brain barrier (BBB), increasing the susceptibility of the central nervous system (CNS) to both primary and metastatic cancers. As the BBB deteriorates, it promotes tumor cell infiltration, alters drug permeability, and contributes to a proinflammatory microenvironment that supports tumor progression. These age-related changes present major obstacles in the effective treatment of CNS malignancies in elderly patients.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This review synthesizes current literature on the mechanisms of BBB aging and its impact on CNS cancer development and treatment. It examines key structural alterations, such as tight junction protein loss, endothelial dysfunction, and pericyte reduction, as well as functional changes including impaired immune regulation and transporter dysfunction. The review also evaluates therapeutic challenges and emerging strategies to overcome the BBB barrier in the aging brain.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Aging induces BBB dysfunction by weakening cellular junctions, disrupting the neurovascular unit, and promoting chronic neuroinflammation. These alterations facilitate tumor cell entry and survival in the brain and reduce the effectiveness of cancer therapies due to impaired drug delivery. Promising interventions, including nanoparticle-based therapies, focused ultrasound techniques, and targeted chemoimmunotherapy, are under development to enhance therapeutic outcomes in elderly patients.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>The age-related breakdown of the BBB contributes significantly to increased cancer risk and therapeutic resistance in the CNS. Addressing BBB dysfunction through age-specific interventions and advanced drug delivery strategies is critical to improving outcomes for older adults with CNS malignancies. Further research into the molecular pathways of BBB aging will support the development of personalized and effective treatments.</p>\n </section>\n </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"6 2","pages":"46-53"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.70002","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging and cancer","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/aac2.70002","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Aging significantly affects the structural and functional integrity of the blood–brain barrier (BBB), increasing the susceptibility of the central nervous system (CNS) to both primary and metastatic cancers. As the BBB deteriorates, it promotes tumor cell infiltration, alters drug permeability, and contributes to a proinflammatory microenvironment that supports tumor progression. These age-related changes present major obstacles in the effective treatment of CNS malignancies in elderly patients.

Methods

This review synthesizes current literature on the mechanisms of BBB aging and its impact on CNS cancer development and treatment. It examines key structural alterations, such as tight junction protein loss, endothelial dysfunction, and pericyte reduction, as well as functional changes including impaired immune regulation and transporter dysfunction. The review also evaluates therapeutic challenges and emerging strategies to overcome the BBB barrier in the aging brain.

Results

Aging induces BBB dysfunction by weakening cellular junctions, disrupting the neurovascular unit, and promoting chronic neuroinflammation. These alterations facilitate tumor cell entry and survival in the brain and reduce the effectiveness of cancer therapies due to impaired drug delivery. Promising interventions, including nanoparticle-based therapies, focused ultrasound techniques, and targeted chemoimmunotherapy, are under development to enhance therapeutic outcomes in elderly patients.

Conclusion

The age-related breakdown of the BBB contributes significantly to increased cancer risk and therapeutic resistance in the CNS. Addressing BBB dysfunction through age-specific interventions and advanced drug delivery strategies is critical to improving outcomes for older adults with CNS malignancies. Further research into the molecular pathways of BBB aging will support the development of personalized and effective treatments.

Abstract Image

查看原文本刊更多论文

衰老驱动的血脑屏障功能障碍及其对中枢神经系统癌症易感性的影响：一项全面的叙述综述

衰老会显著影响血脑屏障（BBB）的结构和功能完整性，增加中枢神经系统（CNS）对原发性和转移性癌症的易感性。随着血脑屏障的恶化，它促进肿瘤细胞浸润，改变药物的渗透性，并有助于促进炎症微环境，支持肿瘤的进展。这些与年龄相关的变化是有效治疗老年患者中枢神经系统恶性肿瘤的主要障碍。方法综述目前有关血脑屏障老化机制及其对中枢神经系统肿瘤发展和治疗影响的文献。它检查了关键的结构改变，如紧密连接蛋白丢失、内皮功能障碍和周细胞减少，以及功能改变，包括受损的免疫调节和转运蛋白功能障碍。该综述还评估了治疗挑战和克服脑屏障老化的新策略。结果衰老通过削弱细胞连接、破坏神经血管单元、促进慢性神经炎症等途径诱导血脑屏障功能障碍。这些改变促进了肿瘤细胞在大脑中的进入和存活，并由于药物传递受损而降低了癌症治疗的有效性。包括纳米颗粒疗法、聚焦超声技术和靶向化学免疫疗法在内的有前景的干预措施正在开发中，以提高老年患者的治疗效果。结论与年龄相关的血脑屏障破坏显著增加了中枢神经系统癌症风险和治疗抵抗。通过年龄特异性干预和先进的药物输送策略解决血脑屏障功能障碍对于改善老年中枢神经系统恶性肿瘤患者的预后至关重要。进一步研究血脑屏障老化的分子途径将有助于开发个性化和有效的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Aging and cancer

CiteScore

0.10

自引率

0.00%

发文量