The Impact of Aging and Age-Related Comorbidities on Stroke Outcome in Animal Models and Humans

Age is the only one non-modifiable risk of cerebral ischemia. Advances in stroke medicine and the adaptation to stroke risk factors and comorbidities were successful in decreasing stroke incidence and increasing the number of stroke survivors in western societies. Comorbidities aggravate the outcome after cerebral ischemia. However, due to the increased in the number of elderly, the incidence of stroke has increased again paralleled by an increase in the number of stroke survivors, many with severe disabilities, that has led to an increased economic and social burden in society. Animal models of stroke often ignore age and comorbidities frequently associated with senescence. This might explain why drugs working nicely in animal models fail to show efficacy in stroke survivors. Since stroke afflicts mostly the elderly comorbid patients, it is highly desirable to test the efficacy of stroke therapies in an appropriate animal stroke model. In this review, we make parallels between animal models of stroke and clinical data and summarize the impact of aging and age-related comorbidities on the efficacy of various therapies and stroke outcome. We conclude that the unsuccessful bench-to-bedside translation of therapies that showed efficacy in young animal models, to aged stroke comorbid patients, is, most likely, due to the negative impact of comorbidities and advanced age on the efficacy of restorative therapies.