Blood-brain barrier dysfunction in aging is mediated by brain endothelial senescence

BBB dysfunction during aging is characterized by an increase in its permeability and phenotypic alterations of brain endothelial cells (BECs) including dysregulation of tight junction's expression. Here we have investigated the role of BEC senescence in the dysfunction of the BBB. Our results suggest that the transition from young to aged BBB is mediated, at least in part by BEC senescence. The current study shows that the accumulation of senescent brain endothelial cells (BECs) may mediate the transition from a young to an aged BBB. Aged BECs have a higher expression of senescent markers and impaired occludin expression which interferes with BBB function. These phenotypes were partially reverted after the systemic elimination of p16+ cells by genetic means. The study contributes for a better understanding of BBB dysfunction during aging.image