Cellular senescence and the blood-brain barrier: Implications for aging and age-related diseases

The blood-brain barrier (BBB) is a critical physiochemical interface that regulates communication between the brain and blood. It is comprised of brain endothelial cells which regulate the BBB's barrier and interface properties and is surrounded by supportive brain cell types including pericytes and astrocytes. Recent reports have suggested that the BBB undergoes dysfunction during normative aging and in disease. In this review, we consider the effect of cellular senescence, one of the nine hallmarks of aging, on the BBB. We first characterize known normative age-related changes at the BBB, and then evaluate changes in neurodegenerative diseases, with an emphasis on if/how cellular senescence is influencing these changes. We then discuss what insight has been gained from in vitro and in vivo studies of cellular senescence at the BBB. Finally, we evaluate mechanisms by which cellular senescence in peripheral pathologies can indirectly or directly affect BBB function.

Automated summary

The blood-brain barrier (BBB) is an important interface that regulates communication between the brain and blood. It is comprised of brain endothelial cells and is surrounded by supportive brain cell types. Recent studies have shown that the BBB undergoes dysfunction during aging and in diseases, and cellular senescence, one of the hallmarks of aging, is believed to play a role in these changes. This review summarizes the known age-related changes at the BBB, evaluates the impact of cellular senescence in neurodegenerative diseases, discusses insights from in vitro and in vivo studies, and explores mechanisms by which cellular senescence affects BBB function.