The pathobiology of neurovascular aging.

IF 14.7 1区 医学 Q1 NEUROSCIENCES Neuron Pub Date : 2025-01-08 DOI:10.1016/j.neuron.2024.12.014
Monica M Santisteban, Costantino Iadecola
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Abstract

As global life expectancy increases, age-related brain diseases such as stroke and dementia have become leading causes of death and disability. The aging of the neurovasculature is a critical determinant of brain aging and disease risk. Neurovascular cells are particularly vulnerable to aging, which induces significant structural and functional changes in arterial, venous, and lymphatic vessels. Consequently, neurovascular aging impairs oxygen and glucose delivery to active brain regions, disrupts endothelial transport mechanisms essential for blood-brain exchange, compromises proteostasis by reducing the clearance of potentially toxic proteins, weakens immune surveillance and privilege, and deprives the brain of key growth factors required for repair and renewal. In this review, we examine the effects of neurovascular aging on brain function and its role in stroke, vascular cognitive impairment, and Alzheimer's disease. Finally, we discuss key unanswered questions that must be addressed to develop neurovascular strategies aimed at promoting healthy brain aging.

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神经血管老化的病理生物学。
随着全球预期寿命的延长,与年龄有关的脑部疾病,如中风和痴呆症,已成为导致死亡和残疾的主要原因。神经血管的老化是脑老化和疾病风险的关键决定因素。神经血管细胞特别容易受到衰老的影响,衰老会导致动脉、静脉和淋巴管的结构和功能发生显著变化。因此,神经血管老化损害氧气和葡萄糖输送到活跃的大脑区域,破坏血脑交换所必需的内皮运输机制,通过减少潜在有毒蛋白质的清除而损害蛋白质平衡,削弱免疫监视和特权,并剥夺大脑修复和更新所需的关键生长因子。在这篇综述中,我们研究了神经血管老化对脑功能的影响及其在中风、血管性认知障碍和阿尔茨海默病中的作用。最后,我们讨论了必须解决的关键问题,以发展旨在促进健康大脑衰老的神经血管策略。
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来源期刊
Neuron
Neuron 医学-神经科学
CiteScore
24.50
自引率
3.10%
发文量
382
审稿时长
1 months
期刊介绍: Established as a highly influential journal in neuroscience, Neuron is widely relied upon in the field. The editors adopt interdisciplinary strategies, integrating biophysical, cellular, developmental, and molecular approaches alongside a systems approach to sensory, motor, and higher-order cognitive functions. Serving as a premier intellectual forum, Neuron holds a prominent position in the entire neuroscience community.
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