The aging of the blood vessels supplying the brain into a state of dysfunction provides an important contribution to the onset and progression of neurodegenerative conditions. There are many aspects to this vascular aging, including: loss of capillary density over time that reduces the ability of the vasculature to deliver sufficient nutrients to cells in brain tissue; the atherosclerosis that narrows and weakens major vessels with fatty deposits; the disruption of normal function of the endothelium, the inner layer of blood vessels; disruption of the normal function of the smooth muscle that controls contraction and dilation of vessels; leakage of the blood-brain barrier, the specialized cells that line blood vessels in the brain and control which molecules are allowed to pass; and so forth. Aging is a disruption of all normal functions, in one way or another.
In today's open access review, researchers take at look at the phenomenon of endothelial-to-mesenchymal transition, a feature of aging in which endothelial cells change their state and behavior to take on the characteristics of mesenchymal cells. This is detrimental to the function of surrounding tissue, which depends on cells of a specific type continuing to act as that type. As the authors note, while the causes of endothelial-to-mesenchymal transition are only partially understood, there is evidence to link its occurrence to mechanisms of aging, and particularly to the chronic inflammatory signaling that is a feature of aged tissues. There are many ways in which continual, unresolved inflammation changes cell behavior for the worse, making it an important target for future medical control over aging.
Age-related dysfunction of the central nervous system, including cognitive impairment and visual disorders, is a major concern for the aging population, affecting health span and quality of life. Age-related vascular dysfunction in the central nervous system includes an increase in blood-brain or blood-retina barrier permeability, an increase in vascular fragility, and impaired neurovascular coupling, contributing to cognitive impairment and vision loss. While these pathologies occur in the brain and eye with age, gaps remain in our understanding of the underlying cellular mechanisms.
During the process of endothelial-to-mesenchymal transition (EndMT), endothelial cells lose their characteristic endothelial phenotypes, which are critical for vascular function, such as barrier integrity, and transition to a mesenchymal-like phenotype. Too little is understood regarding the interplay between triggers associated with physiological aging and the process of EndMT in both non-disease and disease-related contexts in the central nervous system. This highlights a field ripe for exploration, as many age-related processes have also been shown to be triggers of EndMT. For example, many of the inflammatory factors found in the senescence-associated secretory phenotype generated by senescent cells are triggers of EndMT.
Here, we review what is known about the role of EndMT in vascular fragility in the aging brain and eye, explore the mechanistic links between endothelial cell transdifferentiation and age-associated vascular pathologies of the central nervous system, and identify potential therapeutic targets ripe for future exploration with the goal of preserving vascular function with aging by regulating EndMT.
View the full article at FightAging
