Santisteban Monica M, Iadecola Costantino
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Neuron. 2025 Jan 8;113(1):49-70. doi: 10.1016/j.neuron.2024.12.014.
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.
随着全球预期寿命的增加，中风和痴呆等与年龄相关的脑部疾病已成为死亡和残疾的主要原因。神经血管系统的老化是脑老化和疾病风险的关键决定因素。神经血管细胞尤其容易受到衰老的影响，衰老会在动脉、静脉和淋巴管中引发显著的结构和功能变化。因此，神经血管老化会损害向活跃脑区的氧气和葡萄糖输送，破坏血脑交换所必需的内皮运输机制，通过减少潜在毒性蛋白的清除来损害蛋白质稳态，削弱免疫监视和免疫豁免，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，我们讨论了为制定旨在促进健康脑老化的神经血管策略而必须解决的关键未决问题。
