Springer International Publishing 2016. Ischemic stroke is a complex disease with a growing multitude of risk factors. Aging is the principal risk factor for ischemic stroke, such that stroke occurs more often, and is more severe, in older demographics. Furthermore, among this population, stroke is more frequent and more severe in females as compared to males. This review will first describe the clinical literature on the prevalence of stroke as a function of age, sex, ethnicity and co-morbid conditions, and assess the validity of the statement that age is a non-modifiable risk factor for stroke. This is followed by a discussion of the experimental literature, focusing on the utility of animal models in duplicating age-related severity in stroke outcomes, as well as the mechanism underlying severe stroke outcomes. This review will build the case for the hypothesis that stroke severity in the aging brain is associated with, prior to the event, reduced functional capacity of critical support cells, both within the nervous system and in the immune system. In the brain, astrocytes, microglia and endothelial cells are crucial for detoxification of the brain microenvironment and maintaining neuronal survival in the hours following an ischemic event, while recruitment of peripheral immune cells to the brain also determines the eventual stroke outcome. This chapter will further describe epigenetic changes and age-associated susceptibility to stroke.
