How did you discover how blood brain barriers contribute to neurodegeneration and aging?

We took a young mouse, and all we did is open the blood brain barrier and take the one protein from the blood and infuse it into the brain. That was enough to mimic an aged brain, with the specific four phenotypes that do so, in a young mouse. So we can gain the function, but can we lose it. So, there’s a receptor that gets activated by the blood protein, and we eliminate it from the astrocytes. The neurons are all the same, but now we’re taking an aged brain and eliminating that receptor so it can’t get activated. By doing this, we rescue the aging phenotype. We started by doing this in middle age and showing that they don’t age, but then we wanted to look at reverse aging. We were wondering, can you take a brain that’s already aged and reverse it? If it is cell death, then there’s not much you can recover. But, if the plasticity is still there and just masked by the inflammatory response, then you might be able to reverse this. And we were able to do so. We took an aged brain, eliminated this receptor, and it reversed to the phenotype of a young age. This was in mice.