Dr. Patrick:  Chronic inflammation is a major driver in the breakdown and leakiness of the blood-brain barrier. The pericyte cells, guardians of the barrier, have to physically get out of the way to respond to neuroinflammation, letting immune cells in, and ultimately promoting leaks. This leads to a vicious cycle, culminating in loss of capillaries and neurons.

Many factors promote inflammation, obesity, being sedentary, excessive alcohol intake, and smoking, among others. We can't pick our genes, but reducing these factors in our lives will improve our aging.

Dr. Montagne: As we age, there is a phenomenon called inflammaging, so it's a contraction of inflammation in aging. And there is several things happening as we age. There is what's called the seven pillars of aging, which basically has...there are seven things that overlap between normal aging and neurodegenerative diseases. And out of these seven, the central one is inflammation. So, as we age, we have more inflammation going on and we know that there is more cell adhesion molecules. So, these cell adhesion molecules start to be expressed at the endothelial, which is normally not there or in very minimal quantity, and we start having a significant amount of these cell adhesion molecules throughout the whole body.

And the brain is very sensitive to that because these cell adhesion molecules, what they do is they collect the immune cells from the brain...from the blood, sorry, to bring them into the brain. The more you have, the more inflammation...what we call neuroinflammation, the more inflammation you have in your brain. So, that's a normal aging process. And the fact that those endothelial cells turn into a proinflammatory phenotype, the pericytes that are right next to them will...so, there is a crossover. I won't go into details, but the pericytes will have to detach to let the immune cells go through. Physically, if the pericyte stays attached to the vessel, there is no possibility for the immune cells to go through and do their job. So, the fact that there is more inflammation of the vasculature as we age, there is more detachment...I would say physiological detachment of brain pericytes. That's one thing. And there is some report that as we age, there is less...we don't have the capability...I mean, the pericyte don't have the capability to reattach as we can do as we are young.