Normal function of all tissues depends on adequate blood flow. 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. With age, 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. This presentation will review research studies that address the regulation of the cerebral microvasculature during aging (or models that simulate aging). In addition, we will discuss the role of growth hormone and insulin-like growth factor-1 in the regulation of vascular and brain function since these hormones decrease with age and have been implicated in the vascular rarefaction that occurs with age. Finally, we hypothesize that alterations in cerebral blood flow due in part to alterations in IGF-1 have diverse effects on age-related cognitive impairment.

Support: 

NIA grant AG11370.