Deletion of α5 integrin in endothelial cells ameliorates age–associated cognitive decline and increases survival in mice.

Abstract

Levels of inflammatory components gradually rise in tissues and blood as we age. This “inflammageing” process is often debilitating and even fatal. Cognitive impairment is one example of inflammageing’s incapacitating nature. Excessive permeation of inflammatory markers in the brain gradually erodes the blood‐brain barrier (BBB) over time. Consequently, enhanced cerebral inflammatory processes contribute to neurological senescence. Neurological inflammageing may be partly due to a5 integrin, a receptor found primarily in brain endothelial cells during brain development, cerebrovascular injury (e.g. stroke), neuroinflammation and neurodegenerative disease (e.g. ALS). We hypothesize that deletion of a5 integrin in endothelial cells helps maintain BBB integrity and leads to improved cognitive performance with age. In the past we have shown that endothelial cell selective a5 knockout (a5‐EC‐KO) mice are more resilient to ischemic stroke. Enhanced stroke recovery in a5‐EC‐KO mice is due to less a5‐related BBB deterioration and subsequently less brain edema and infiltration of peripheral inflammatory cells. Therefore, we used aged a5‐EC‐KO and wild type (WT) litter mate mice to investigate how a5 integrin influences cognitive performance and survival probability over time.