Can we slow down how quickly our brain ages?

As the brain ages, we see a decline in cognitive function, and the risk of neurodegenerative diseases like dementia begins to rise. Scientists have long sought to identify the factors responsible for ageing, but now new research suggests rather than looking just inside the brain, maybe we should be looking at what surrounds it too. That’s the cerebrospinal fluid, in which the brain floats. Julia Ravey spoke with Tony Wyss-Coray to find out more…

Tony - We know that the spinal fluid composition changes dramatically with age in mice and in people. We asked whether the spinal fluid from young mice could have a positive effect on the brains of old mice and, most importantly, improve their function.

Julia- And what did your results show when you tried to apply this by putting the young spinal fluid into the older mice?

Tony - We found, indeed, that young spinal fluid seems to have factors that are beneficial for the old brain. Most importantly, it improved the memory of these mice. And so they could better remember a task that we taught them a few days earlier.

Julia - Did they revert right back to the age of the young mice, or was it just a bit of an improvement?

Tony - We definitely see a very prominent improvement. We compared mice that have an equivalent to about a 65 year old person and, if I had to estimate, maybe we get their memory back to a 45 year old or something like that. So, pretty good.

Julia - And do you think these changes may revert once the spinal fluid replenishes itself, or could this infusion have longer lasting effects?

Tony- We believe that there are effects that last for several weeks, that's the length of our experiment, but it's possible that it actually lasts even longer because we actually make more cells with this experimental intervention. We can induce the production of cells that the brain uses to form memories and to recall memories.

Julia - And would there be a way that we could maybe make this up synthetically? So that doing this type of experiment and getting these effects is a bit easier?

Tony - We were able to identify at least one factor that seems to mimic these effects of the young spinal fluid. And this factor, we can actually produce synthetically. We obtained this factor, and when we now infuse this factor alone, it mimics many of the effects that we see with the young spinal fluid. This is very encouraging because it suggests that we could potentially mimic this effect, even in humans, where we would potentially also infuse this factor, or maybe find other ways; find small molecule drugs that can mimic the effect and drugs that you could take as a tablet. The drug would then get into the brain and have similar effects. Now, we're still a long ways to go but, in principle, this approach is feasible, we think.

Julia - That's still a pretty good improvement. And this work was all done in mice, so if we're thinking more about the translational impact with humans, what do you think this research tells us about, in general, how the brain's function is regulated by the environment it's in and then also translational in terms of these later life neurodegenerative diseases. Could utilising the spinal fluid, or the factors within it, help with some of these diseases?

Tony - What we're trying to do is understand brain ageing, neurodegeneration, not so much from the perspective of the pathology and the disease, but we're trying to see how we can keep the brain healthy for as long as possible, as long as you live. What we found is that the environment in which the brain resides, so this spinal fluid, has a big impact on how the brain ages, and there may be factors in there - more than the one we discovered - that we can harness and use to keep brains young and maintain their functionality until people die.