Reviewing the Link Between Peripheral Vascular Aging and the Brain

The development of cardiovascular disease outside the brain is thought to contribute to the aging of the brain. The brain is an energy-hungry tissue, and any reduction in blood flow, such as through atherosclerotic narrowing of the arteries and heart failure, will cause harm and functional decline over time. At the same time, and while every organ influences every other organ in some way, it is also the case that vascular aging and brain aging arise to some degree independently due to same underlying processes of aging that operate in every tissue. Mitochondrial dysfunction occurs in the brain just as much as it does in the vasculature, for example, and for reasons centered on the cell, not on the tissue - such as epigenetic changes that occur due to nuclear DNA double strand break repair, or stochastic mutation of mitochondrial DNA.

Aging is the greatest non-modifiable risk factor for most diseases, including cardiovascular diseases (CVD), which remain the leading cause of mortality worldwide. Robust evidence indicates that CVD are a strong determinant for reduced brain health and all-cause dementia with advancing age. CVD are also closely linked with peripheral and cerebral vascular dysfunction, common contributors to the development and progression of all types of dementia, that are largely driven by excessive levels of oxidative stress, e.g., reactive oxygen species (ROS). Emerging evidence suggests that several fundamental aging mechanisms (e.g., "hallmarks" of aging), including chronic low-grade inflammation, mitochondrial dysfunction, cellular senescence, and deregulated nutrient sensing contribute to excessive ROS production and are common to both peripheral and cerebral vascular dysfunction.

Therefore, targeting these mechanisms to reduce ROS-related oxidative stress and improve peripheral and/or cerebral vascular function may be a promising strategy to reduce dementia risk with aging. Investigating how certain lifestyle strategies (e.g., aerobic exercise and diet modulation) and/or select pharmacological agents (natural and synthetic) intersect with aging "hallmarks" to promote peripheral and/or cerebral vascular health represent a viable option for reducing dementia risk with aging. Therefore, the primary purpose of this review is to explore mechanistic links among peripheral vascular dysfunction, cerebral vascular dysfunction, and reduced brain health with aging. Such insight and assessments of non-invasive measures of peripheral and cerebral vascular health with aging might provide a new approach for assessing dementia risk in older adults.


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