What does the science say when it comes to healthy ageing? In this episode of A Grey Matter we speak to pioneering neuroscientist Professor Perry Bartlett about healthy ageing and how the brain regenerates itself.
 

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Donna:  Aging. We start doing it from the moment we're born. Society is obsessed with it and everywhere we look we're confronted with anti-aging creams, exercise programs and a plethora of buzzwords like healthy, useful and rejuvenate.  But what does the science say when it comes to healthy aging? On this episode of A Grey Matter we speak to pioneering neuroscientist Professor Perry Bartlett about healthy aging and the brain's ability to regenerate. At the University of Queensland, Perry is a foundation professor of molecular neuroscience and was the inaugural director of the Queensland Brain Institute. Perry made the groundbreaking discovery that stem cells exist in the adult brain meaning that the brain can regenerate by producing new cells. He was awarded the prestigious C.S.L. Florey medal in 2015 and this year was a finalist in the Queensland Australia of the Year Awards. Perry talks about stem cells in the adult brain, exercise and how our brains change as we age.

Prof Bartlett:  It was in the early 1990s, in fact, we probably started working on this in the late 1980s; and it followed on from work we've been doing looking at trying to understand how the brain generates so many neurons because as you know in the human brain there are around hundred billion neurons. So, each of which makes 10,000 connections, so the actual amount of complication in terms of circulatory is enormous. And we discovered that in the developing brain, there were these populations of cells that gave rise to many, many neurons and they were called stem cells - which is not surprising, you know, developing animals making so many new nerve cells - but we thought, well, if they're really true stem cells, one of the properties would be that they can self-renew; that is, they keep making more themselves. And so we decided to test this hypothesis by looking in the adult brain of mice.And to our great surprise we found there were cells that can make new neurons. Now, the time we thought that was damn interesting because everyone thought that wasn't impossible that adult brain cells, brain cells could be made in the adult. How we didn't know what the functional or significance of it was, we thought perhaps it was just a remnant of development and you know, could possibly be interesting in terms of being how to repair damaged brains in the adult, but we had no inkling that in fact it might be more fundamental than that.

Donna:  Can you tell us about neuroplasticity and the ability of the brain to regenerate itself?

Prof Bartlett:  Well, neuroplasticity is a word that's used a lot and it means a lot of different things to a lot of different people. At one level, the most common neuroplasticity is the ability of no cells to make new connections and virtually everything we learned or memorised is due to connections being changed, reinforced or diminished. So, the production of new neurons is that is another element of this. The ability of these new neurons to integrate into the circuitry and change things like learning and memory is something that offers a far greater degree of plasticity than we ever thought. So, neural plasticity really is this malleability of the brain to change, and that change usually is the functional mechanism by which learning and memory and behavioral characteristics occur.

Donna:  Are there factors that affect neuroplasticity?

Prof Bartlett:  Well, there are a lot of things that affect neuroplasticity in terms of connections between neurons, which are called synapses – this gap between neurons in which chemicals are transferred and information is transferred. There are enormous numbers of molecules that are involved in that transmission and regulating that transmission. We've been focused on trying to understand how new neurons are regulated because what we’ve discovered, more recently, is that in one part of the brain, the hippocampus – it’s called the hippocampus because it looks like a seahorse – and this area in the humans is probably the only area where new nerve cells are made throughout life. And, you know, the exciting thing here is that the hippocampus is probably the most important part of the brain that processes information and forms new memories, especially memories about when and where something happened? How you can navigate from A to B, you know when you met someone where you left your keys, etc…etc. The sort of memories that came to decline in some percentage of older people, not all old people.

Donna: So, what happens in the brain or particularly in the hippocampus as we age? 

Prof Bartlett:  Well, I think it's become very interesting and you know, somewhat negative is that there's a sense around that somehow that it's inevitable that the hippocampus shrinks and become smaller with age and this finding is true to some degree, but the interesting thing is because the production of nerve cells can occur in the hippocampus this appears to be reversible. So, while you can get shrinkage in hippocampus, there is certainly evidence now that you could change that – reverse that shrinkage and reverse any loss of learning in memory by stimulating both the production of these new nerve cells, but also stimulating greater connectivity within the hippocampus. So, the hippocampus has become a bit of a canary in the coal mine, that is the first thing that really starts to change in older people. These functions associated with the hippocampus and the changes in the size of the hippocampus can be picked up using very high-end technologies like imaging, whereby we can we can image down to almost single cells within the hippocampus.

Donna:  In terms of the behavioral changes or symptoms of that change, are they easily detectable?

Prof Bartlett:  Well, in the early stages not so much, but certainly, obviously, with one in three people over the age of 85 having significant impairment, by which they really are functionally impaired – that is, they literally don't remember where or where they left something or how to navigate home and things like that. Obviously it does become very, very clear.  And there's a lot of controversy around the early stages; there’s this thing called mild cognitive impairment, which many people get labelled with, but whether they really have something that's going to lead to Alzheimer's or not or dementia is still not clear. And I think everyone knows that there are periods that individuals suffer some mild cognitive impairment due to medication or some severe stress. So, I think we're not very good at picking up these early changes and that's largely because they're not too many good tests for hippocampal function. A lot of the test given by clinicians are very broad and not very specific, so one of the things we're trying to do is very much look at how hippocampal changes and reversal of hippocampal changes can affect that hippocampal base memory and learning.

Donna:  Is there a difference between being forgetful, say forgetting where you parked or left your keys and a diagnosable cognitive impairment?

Prof Bartlett:  Well, I think everyone's forgetful. I think when it becomes… when it becomes obvious is this inability to form new memories. That is, a lot of people can remember things from 40-50 years ago, 10 years ago, but they can't remember you know, what they had for lunch or something, or where they were early in the day. So, when it becomes obvious that you’re not, you’re starting to become incapable of taking that information around you and putting it into memory I think that's when… that's what the hippocampus does; it takes all of these visual information, information from hearing, information from emotions and it's all processed through the hippocampus. So, once you stop being unable to take that information from your environment and form these memory pieces, then that's when things are going awry.

Donna:  What we do know is that it a cognitive impairment doesn't affect everyone. Do we know why that is? Why some people experience cognitive decline, but others are totally unaffected?

Prof Bartlett:  Well, I think… I think this is the good news. And the good news is that even though the incidence of dementia is directly related to age – the age is the greatest predisposing – there's nothing to say it's inevitable and there are several cases of very old people being tested. One particular case that's been published is a lady was 113 who had cognitive testing and then she died two years later and they were able to look at the number of nerve cells in her brain and A): She had cognitive abilities of somewhere around 40 or 50 and B): The number of nerve cells in the areas they looked at was not significantly reduced compared to someone of 40 or 50. So, this old… this old adage that you know it's all downhill because you're getting older is not true. So, in terms of inevitability, it’s certainly not inevitable. So, one of the factors; well, in terms of the hippocampus obviously what we've shown in animals is that… in old animals suffer the same decline in their abilities to learn to learn to navigate, which is a very strong hippocampal base function. And these animals show a decrease in the hippocampus. But the good news is, as I said, although it's a canary in the coalmine and it’s the first thing to start to show changes by the structural and functional, we’ve shown that it's able to be reversed. And by activating the production of new nerve cells through exercise, we've been able to show that you can reverse this cognitive decline. So, the hope is and the data supports this, that there been a few studies that show exercise to be beneficial both in terms of using imaging M.R.I. (magnetic resonance imaging), to show increase in a size of the hippocampus with exercise over a 12-month period and the same thing has happened in animals, we’re able to show. So, the sixty-four-billion- or trillion-dollar question is: What are the best forms of exercise and how long do you need to do it in order to obtain this reversal or at least debility to slow down any loss in the hippocampus? And, that's really what we're trying to understand in the study that we've just started just three months ago.

Donna:  So, just to clarify that's a human clinical trial that you're leading at the moment?

Prof Bartlett:  That's right! So, we we’re fortunate to get funds to test our hypothesis that there might be very discrete levels of exercise that cause changes in the hippocampus, that we're measuring by, again, with the world's biggest magnet… to be able to look at very subtle changes in the hippocampus along with using a lot of blood chemistry to try and look for changes in the blood that correspond to the right level of exercise. And very strictly supervise levels of exercise. Three levels of exercise including one that's quite… is quite high intensity whereby you working about 80 or 90% of your… of your maximum level. So, it's a very comprehensive study. The most comprehensive studies ever been because I think there's so much anecdotal hearsay out there about how much exercise one should do without any basis, real scientific basis, that if we’re going to understand this we need to do a very, very focused, and measure all parameters we can, in terms of what's changing in humans that can undergo this regeneration.

Donna:  Your research in animal models has found that it's not necessarily a case of the more exercise the better.

Prof Bartlett:  Well, that's right! That's… that's one of the surprises and one of the driving forces here was that in these old mice, we were able to show that this seems to be an optimal amount of exercise, at least in this improvement. And if too much exercise, in fact had no effect, like too little. And we think this is related to obviously to release of factors in the blood which we’re starting to understand in the mice, and that's what we're looking for - factors in the human to see if there's a peak release associated with certain forms of exercise. So, the good news for all those people out there who are like me you don't do enormous amount of exercise, is at the optimal level may not be running, you know, for an hour each day. It might be a lot less. And the other thing might be that in these animals we show that once activated, once we can start to stimulate the production of these new nerve cells and change the hippocampus, that perhaps that might be longer lasting, so you might not have to exercise all the time. You might have to exercise perhaps once every six months or something. I don't know, but you know.  

Donna:  That would be the dream, wouldn’t it?

Prof Bartlett:  Well, I don't know. I think exercise obviously has other beneficial effects in terms of… in terms of heart and things like that. But I think the message here also is that for a long time we thought what's good for your heart and what's good for the brain are the same things. I think the more we're learning it, you know, it's not necessarily true what's good for your heart is good for your brain.

Donna:  That was Professor Perry Bartlett on Healthy Ageing. If you're interested in participating in the human exercise study at the University of Queensland, please e-mail healthybrains@uq.edu.eu or you can visit the Queensland Brain Institute website qbi.uq.edu.au and click on the Get involved tab. That's all for this episode. I'm Donna Lu. Our podcast as always is produced by Jessica McGaw. If you enjoyed this episode, let us know on Twitter or Facebook. Share it with your friends or you can give us a review on iTunes. Thanks for listening. 

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