Normal function of virtually all tissues depends on adequate blood flow. As one would expect, deficits in blood flow under basal or stimulated conditions result in diminished metabolic capacity and impairments in function. Importantly, functional deficits in organs and tissues are one of the hallmarks of biological aging but the etiology of these deficits and the potential relationship between alterations in blood flow and the deterioration of tissue function with age remain enigmatic. Empirical and rigorous scientific evidence demonstrates that functional deterioration of many tissues begins in early adulthood and progresses throughout life. Concurrently, there is an increase in tissue pathology, including deposition of insoluble collagen and tissue fibrosis. Despite the structural changes with age, which are generally considered permanent or irreversible, tissue function can be improved even in late ages by several disparate types of interventions, supporting the conclusion that age-related impairments in cellular and tissue function, and perhaps some aspects of aging itself, remain “plastic.” Whether such “plastic” changes depend on increased basal blood flow or the capacity to increase blood flow in response to metabolic challenge remains unknown. The strong relationship that exists between cellular metabolic capacity and regional blood flow leads to the conclusion that a clear understanding of age-related changes in the regulation of blood flow (including microvascular architecture, plasticity, and vessel reactivity) is essential for understanding the progressive decline in cellular metabolic activity and eventually tissue function with age. Nevertheless, there are a limited number of studies that have considered the potential interrelationships between these variables. The guiding principle of this chapter, and for which there remain insufficient data, is that alterations in the vasculature have the capacity to impact biological aging. These alterations may include, but are not limited to, changes in microvascular density (density of arterioles, arteriolar to arteriolar anastomoses, capillaries, and venules); ultrastructure (cellular components that comprise the vasculature); plasticity (e.g., elaboration, regression, or replacement of microvessels that may occur over days, weeks, or months); and the dynamic regulation of blood flow through the vasculature (e.g., vessel reactivity). Despite the importance of each of these components, historical and technical aspects of research in these areas isolate the scientific disciplines and they are rarely considered a functional unit. This chapter reviews the current state of information in each of these areas as it relates to functional changes within the central nervous system with age.
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