The pathobiology of neurovascular aging.

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.