Exercise has been shown to be beneficial for cognitive function in aging 
. Regular exercise is associated with various physiological and structural changes in the brain, especially in the hippocampus 
, an area that plays a key role in learning and memory 
. Animal and human studies have highlighted several potential changes in neuronal function by which exercise may promote healthy brain aging including increases in neurotrophic factors, neurogenesis and neuronal plasticity 
. Nevertheless, the effects of chronic exercise on age related changes in glial and cerebrovascular processes are relatively unexplored.
The brain parenchyma is composed of many cell types, but glia, are by far the most numerous 
. It has long been appreciated that astroglial cells are involved in the inflammatory response of the aged brain and that an increase in astrocyte hypertrophy/reactivity is a consistent marker of brain aging across multiple species 
. In addition, the process of myelination, mediated by oligodendroglial cells, is apparently dysregulated with aging 
. Perhaps surprisingly, a number of studies indicate that activation of myelin-related genes/proteins and actual myelination are increased with brain aging 
. Because glial processes regulate many aspects of neuronal function, these changes may have broad implications for the cognitive decline typical of unhealthy brain aging.
Interactions of these glial components of the parenchyma with cerebral blood vessels are also likely to play a critical role in brain aging. With aging, there is a decrease in vascularity and endothelial function which, in turn can affect cerebral perfusion pressure and hemodynamics 
. Because the brain is so highly vascularized and depends on constant and sufficient cerebral blood flow 
, the impact of aging on brain function may depend on the extent to which such changes in the cerebrovasculature occur 
. Further, exercise and the vasoprotection it imparts may play a major role in modifying the extent of brain aging.
At midlife, low levels of physical activity in humans are already considered a risk factor for unhealthy brain aging 
. On the other hand, exercise at this point in the lifespan appears to have significant effects on vascular function 
and, thus, this period appears to represent an age at which significant vascular plasticity is still present. The beneficial effect of exercise may be particularly relevant for aging females as results from the Framingham and Whitehall cohorts show that some vascular risk factors (e.g., hypertension) may have a greater negative impact in women than men 
. Further, aerobic exercise, which positively impacts vascular health 
, appears to confer greater cognitive benefits to aging women 
. Women at midlife also experience hormonal changes, which along with physical inactivity, may further increase their vulnerability to certain aspects of vascular and brain aging 
Interestingly, this period of the lifespan in experimental animal models also coincides with the increased expression of many markers of brain aging, in particular an increase in astrocyte hypertrophy/reactivity and myelin-related changes 
. Although, extensive work has been performed to examine the interactions of exercise with cognitive and neuronal function in aging, very little is known about the effects of exercise on midlife changes in vascular and glial biomarkers of brain aging. As these processes are intimately connected (i.e. astrocytic endfeet directly appose blood vessels in the brain and also appear to activate myelination processes) 
, it could well be that glial and vascular aging changes are of major importance to the cognitive and neuronal changes seen with aging. Therefore, the present studies were undertaken to test the hypothesis that exercise initiated at mid-age can slow the development of hippocampal glial and vascular biomarkers of early aging. Because of apparent selective effects of exercise on vascular and cognitive function in aging women 
, we studied the effects of exercise intervention in a middle-aged female animal model. Our results implicate glial and vascular changes as potential factors contributing to the beneficial effects of exercise on brain aging.