00:00:01 – 00:00:42
VO Victoria
Welcome to Beyond Lab Walls, a podcast from the Salk Institute, a nonprofit foundational research institute bound by collaboration and curiosity, where scientists come together to ask what if. The Salk Institute stands as a landmark monument to science overlooking the Pacific Ocean. Within the iconic Louis Kahn designed architecture, scientists tackle global questions in aging, agriculture, disease, nutrition, sleep, memory, and so much more. Here at Salk, we’re unlocking the secrets of life itself and sharing them beyond lab walls.
00:00:43 – 00:01:10
Gerald
Hello everybody and welcome to a special episode of Beyond Lab Walls, a podcast from the Salk Institute. I’m Salk’s president, Gerald Joyce. And, today we’re going to be talking about brain health, about cognitive brain health as part of Salk’s Year of Brain Health. We’re so lucky to have the brains we have as a species. I mean the human brain is just one of evolution’s greatest inventions.
00:01:10 – 00:01:29
Gerald
You know, it gives us such a rich intellectual and emotional life. But we weren’t quite evolved to live as long as we do. And so there’s a challenge in in keeping that wonderful brain fit over the many decades, the seven to eight decades that is now average lifespan in in the United States.
00:01:29 – 00:01:45
Gerald
So that’s why we’re focusing on the issue of brain health through a long lifespan, cognitive brain health. We’re looking at all different aspects of this, what you can do to maintain brain health through a through a long lifespan.
00:01:45 – 00:02:11
Gerald
So cardiovascular health, metabolic health, immune health, exercise, which we’re going to be talking about today, building cognitive strength, good sleep habits, and so on. We’ve heard all these these sort of recipes for for good brain health. But we want to dig deeper, as as we are through this entire series, and through this year into, why are these good things and how can we learn more about them? And that’s of course what we’re doing here at the Salk Institute.
00:02:11 – 00:02:27
Gerald
It is my pleasure to have as a special guest, Rusty Gage, a world-renowned neuroscientist and my predecessor as president at the Salk Institute. Rusty’s had just a remarkable, continued to have a remarkable scientific career.
00:02:27 – 00:02:51
Gerald
One of his incredible breakthroughs was the surprising finding that we continue to make new neurons in our brain through our entire life into adulthood. People thought that wasn’t the case, but Rusty and his colleagues showed that is possible. This is a process that’s sometimes referred to as neurogenesis. And hopefully Rusty can tell us a bit more about that. So we’re fortunate to have Rusty with us today.
00:02:51 – 00:03:05
Gerald
There’s lots of things we could talk about, Rusty, but I’m hoping because I know you’re also an expert in this aspect of brain health to we want to talk about the relationship between
exercise, between good healthy exercise and good healthy brains over a long lifespan.
00:03:05 – 00:03:24
Gerald
Let’s just kind of start with a general question. So we always hear exercise, exercise.
It’s good for lots of things but we hear that exercise is important for good brain health.
But what’s behind that? Tell us some of the the the biology behind the connection
between good exercise a good brain health.
00:03:24 – 00:03:39
Oxidado
Well, one of the things that is strikingly interesting to people is that while the brain constitutes only 2% of the volume of your entire body, it consumes 20% of the energy. That’s just in steady state.
00:03:39 – 00:03:40
Gerald
Amazing. It’s running hot.
00:03:40 – 00:03:41
Oxidado
It’s running hot.
00:03:41 – 00:03:41
Gerald
De acuerdo.
00:03:41 – 00:03:43
Oxidado
And it needs energy to do that.
00:03:43 – 00:03:43
Gerald
Yes.
00:03:44 – 00:03:49
Oxidado
And the energy comes from their circulation, from the blood, and from our breathing. So, we need air.
00:03:49 – 00:03:50
Gerald
Right. Right.
00:03:50 – 00:03:54
Oxidado
We need to to breathe and we need nutrients to keep going.
00:03:54 – 00:03:54
Gerald
Okay?
00:03:50 – 00:04:02
Oxidado
And the the oxygen that we’re breaking in breaks down the glucose that’s in the in the blood circulating.
00:04:02 – 00:04:02
Gerald
Okay?
00:04:02 – 00:04:06
Oxidado
And it supplies ATP, which is the source of energy.
00:04:06 – 00:04:10
Gerald
So that’s basically the food for the brain pump to the brain. But okay, why exercise?
00:04:10 – 00:04:13
Oxidado
If you exercise, your circulation increases.
00:04:13 – 00:04:14
Gerald
Okay. Right.
00:04:14 – 00:04:26
Oxidado
And what what’s also remarkable are these little machines that are in every cell called mitochondria that make the energy. They’re actually multiplying by virtue of exercise. So the more you exercise, the more energy machine,
00:04:26 – 00:04:32
Gerald
the more mitochondrial capacity you have and the more you can fuel this this amazing organ we have.
00:04:32 – 00:04:49
Oxidado
And you can think about it also as an acute effect of aging. Go out there and do one series about of education. That’s good. That’s that that’s good for you. But the really important thing is the long-term maintenance of it because that increases the efficiency of utilizing all those nutrients in your brain.
00:04:49 – 00:04:50
Gerald
Very good.
00:04:50 – 00:04:51
Oxidado
Set you at a higher level.
00:04:51 – 00:05:02
Gerald
Yeah. And that is the theme of this entire series is what can we do over our entire lifespan to maintain good brain health for a lifespan. So let me ask you, I mean you look fit. What what do you do to exercise?
00:05:02 – 00:05:12
Oxidado
Well I try to balance things out. Every day I stretch and do some light lifting to strengthen my muscles a little bit.
00:05:12 – 00:05:13
Gerald
Stretching is exercise.
00:05:13 – 00:05:26
Oxidado
Stretching is a definitely a form of exercise and you can do it lying down, sitting down, anyway. Just stretching out your muscles, because using any kind of movement at all is a form of exercise.
00:05:26 – 00:05:26
Gerald
De acuerdo.
00:05:27 – 00:05:30
Oxidado
It’s increasing blood flow. It’s increasing the utilization movement.
00:05:30 – 00:05:31
Gerald
Does texting count?
00:05:31 – 00:05:36
Oxidado
Texting probably. You know, it’s all an ingredient. You strengthen your fingers for sure.
00:05:36 – 00:05:37
Gerald
A little.
00:05:37 – 00:05:38
Oxidado
Yeah. But then I do aerobic exercise.
00:05:38 – 00:05:41
Gerald
Oh, so you do aerobics. So, what kind of aerobics?
00:05:41 – 00:05:43
Oxidado
I run. And I run.
00:05:43 – 00:05:44
Gerald
That gets everything going. Very good.
00:05:45 – 00:05:48
Oxidado
Muscles on a regular basis. I try to put in three to four miles a day.
00:05:48 – 00:05:50
Gerald
Okay. Three to four miles a day.
00:05:50 – 00:05:48
Oxidado
Yes.
00:05:51 – 00:05:52
Gerald
Pretty much every day.
00:05:52 – 00:05:52
Oxidado
Every day.
00:05:52 – 00:05:57
Gerald
Good for you. Now, I remember you telling me years ago that you used to be a kickboxer. Am I right about that?
00:05:58 – 00:06:08
Oxidado
When I was younger. Significantly younger. Yes. I did it competitive kickboxing. I did, but I did a lot of different sports, but for a period of time I was a a martial artist.
00:06:08 – 00:06:09
Gerald
Martial arts. Wow. That sounds intense.
00:06:09 – 00:06:09
Oxidado
Sí.
00:06:10 – 00:06:14
Gerald
So that’s that’s full body exercise. That’s agility, that’s strength and that’s aerobic.
00:06:14 – 00:06:24
Oxidado
So but I should say the important part there is no matter what exercise you’re doing to do that exercise well or to do that sport well.
00:06:24 – 00:06:24
Gerald
Sí.
00:06:24 – 00:06:30
Oxidado
You need to be in shape. You need to do chronic exercises to get yourself ready to be able to do that well.
00:06:30 – 00:06:30
Gerald
De acuerdo.
00:06:30 – 00:06:36
Oxidado
So, it’s not just the it’s not just the impact of doing that sport, but it’s preparing yourself for it.
00:06:36 – 00:07:08
Gerald
Okay. So, you can’t just be, a once a month athlete. Then you’re not an athlete. Okay. So, I I’ve already talked about this this remarkable discovery that you and your colleagues made that previously people thought that essentially the number of neurons you have in your brain is
finite. And as you get to adulthood, shows’ over, but you showed that’s not the case. And then
there’s this term called neurogenesis. Can you explain what neurogenesis is and and what we now think about about neurons over the lifespan?
00:07:08 – 00:07:17
Oxidado
So neurogenesis is a process by which a stem cell, a primitive cell, becomes a neuron, becomes a functioning neuron.
00:07:17 – 00:07:18
Gerald
So what is it before it’s a neuron?
00:07:18 – 00:07:37
Oxidado
It’s what’s called a stem cell. It’s a pluripotent cell. It has the opportunity to give rise to lots of good anything. Then it goes to a next phase where it becomes a a neural progenitor cell like it’s on the road. It’s on the road and then it finally gets to a fully functioning neuron which makes all its connections with its environment. So it is a process of maturation.
00:07:37 – 00:07:44
Oxidado
And this is what happens during development. Your brain is being born and before
we’re born
00:07:44 – 00:07:46
Gerald
before this is happening to basically build the brain.
00:07:46 – 00:07:55
Oxidado
We all thought that after we’re born that there’s very little or if any quote neurogenesis all that’s a developmental process.
00:07:55 – 00:08:08
Gerald
Okay. I remember learning in in med school that the neurons are there and all that happens sort of after young childhood, there it’s just making connections but it’s not making neurons but okay but tell us about new neurons.
00:08:08 – 00:08:15
Oxidado
Yes. So we discovered that in one area in particular, so it’s not everywhere in the brain, but in one area in particular called the hippocampus.
00:08:15 – 00:08:15
Gerald
Okay,
00:08:16 – 00:08:24
Oxidado
There are stem cells that are retained in that area throughout life and these stem cells can give rise to new neurons.
00:08:24 – 00:08:26
Gerald
Even in your 60s, 70s, 80s?
00:08:26 – 00:08:40
Oxidado
It turns out even in this the last couple months there have been a few papers showing that in healthy individuals, which is what we’re talking about, you do have an increase in neurogenesis. You have neurogenesis occurring in the 60s and 70s.
00:08:40 – 00:08:42
Gerald
What does the hippocampus do in the brain?
00:08:42 – 00:08:47
Oxidado
So the hippocampus is a structure right here. We call the temporal portion.
00:08:47 – 00:08:48
Gerald
Kind of behind the ear.
00:08:48 – 00:08:59
Oxidado
Behind the ear and this is an area of the brain that’s involved in the acquisition
of new information and the retention of of this information, storing it. So basically memory
and retrieval.
00:08:59 – 00:09:00
Gerald
So your memory and retrieval.
00:09:00 – 00:09:02
Oxidado
So your ability to recall something.
00:09:02 – 00:09:03
Gerald
It’s like our hard drive.
00:09:03 – 00:09:05
Oxidado
This is your hard drive.
00:09:05 – 00:09:07
Gerald
But we make new neurons on the hard drive also.
00:09:07 – 00:09:12
Oxidado
But it also is involved in the acquisition of new memories as well as the hard drive.
00:09:12 – 00:09:13
Gerald
Oh, I see.
00:09:13 – 00:09:16
Oxidado
Survival. Yeah. So it’s a it’s a an important feature.
00:09:16 – 00:09:24
Gerald
So if we’re making new neurons there and maybe in some other places, but not everywhere. I mean, how do we fit it? Because our skull doesn’t change size.
00:09:24 – 00:09:29
Oxidado
So, you know, it turns out that there have been some volumetric measurements of
the effects of of exercise.
00:09:29 – 00:09:29
Gerald
Sí.
00:09:30 – 00:09:34
Oxidado
And it turns out you can increase the size of just this one structure by 15%
00:09:34 – 00:09:34
Gerald
15%
00:09:35 – 00:09:38
Oxidado
over a period of time with chronic exercise.
00:09:35 – 00:09:41
Gerald
And but how does it fit inside our skull if it goes up by 15%?
00:09:41 – 00:09:42
Oxidado
Yeah. So, it’s a small
00:09:42 – 00:09:46
Gerald
It’s a small 15% of a few percent.
00:09:46 – 00:10:03
Oxidado
Exactly right. Exactly right. So if you if for example in this structure just loosely have about 2 million
brain cells, you had hundreds of brain cells, but in this one area you had about 2 million, you’re adding a few. You’re adding several more, 100 thousand more cells, and there’s room for that.
00:10:03 – 00:10:11
Gerald
Okay. Okay. Very interesting. Yeah. I I don’t think people have that general concept that we can keep making new neurons, but only if we’re healthy. I think that was the key thing.
00:10:11 – 00:10:21
Oxidado
That’s the key because in disease we do know that this ability to generate stem cell, generate neurons from stem cells, that’s when it drops off and with cognitive decline.
00:10:21 – 00:10:26
Gerald
And these new neurons actually help cognitive function. They’re not just like there they actually do good work for us.
00:10:26 – 00:10:33
Oxidado
They do and there’s there’s experimental evidence clearly looking at individuals that have
less neurogenesis.
00:10:33 – 00:10:33
Gerald
Sí.
00:10:34 – 00:10:35
Oxidado
They perform less well.
00:10:35 – 00:10:38
Gerald
Okay. And this is people, not animals?
00:10:38 – 00:10:45
Oxidado
This is people and what’s really interesting about this is that it’s still an area of intense investigation, what exactly is being done.
00:10:46 – 00:10:46
Gerald
De acuerdo.
00:10:46 – 00:10:51
Oxidado
But what these new neurons do is they help you to make distinctions between things that are very closely related to each other.
00:10:51 – 00:10:51
Gerald
De acuerdo.
00:10:51 – 00:10:55
Oxidado
So it’s making these fine distinctions in life.
00:10:55 – 00:11:09
Gerald
This is very encouraging to our audience that we’re still building our brains as long as we stay healthy. So I I want to talk about a very special molecule that you have studied quite a bit called brain-derived neurotropic factor, BDNF.
00:11:09 – 00:11:09
Oxidado
Yes.
00:11:09 – 00:11:24
Gerald
All right. Without getting too technical, my understanding is that this is a protein and when you exercise it goes up in in amount and when it goes up it helps neurogenesis. So can can you talk about BDNF?
00:11:24 – 00:11:29
Oxidado
Absolutely. BDNF is a protein in neurons and expressed in neurons and so in in astrocytes.
00:11:29 – 00:11:31
Gerald
It’s in neurons, not in muscle.
00:11:31 – 00:11:32
Oxidado
That’s right.
00:11:32 – 00:11:34
Gerald
But when you exercise it goes up. So
00:11:34 – 00:11:55
Oxidado
It goes up and when it’s increased what it does is it facilitates or it helps the connections that are made between neurons. So you can actually increase the number of connection peers. And think about that with regards to neurogenesis because as these new cells are coming in part of their job is to find how to make new connections and BDNF facilitates that.
00:11:55 – 00:12:04
Gerald
This this is a good point. I think. So it’s not just making new neurons but they’ve got to find good connection and BDNF is sort of the facilitator of good connecting.
00:12:04 – 00:12:13
Oxidado
It also is what we call a survival factor. It helps cells survive and to maintain their integrity for longer periods of time.
00:12:13 – 00:12:19
Gerald
So when neurons are well connected do they survive better or do they survive better and therefore can be well connected?
00:12:19 – 00:12:32
Oxidado
I think the better way to think about it is the former, which is that BDNF facilitates the connections that in that increase in connections facilitates survival.
00:12:32 – 00:12:42
Gerald
Very interesting, because the brain sort of nurtures the connected part of itself. But why does BDNF go up when you exercise? This seems like, brain here, glutes down here.
00:12:43 – 00:12:46
Oxidado
This is a little more biology.
00:12:46 – 00:12:53
Gerald
Don’t go too deep. But there is a connection that is understood to at least to some extent.
00:12:53 – 00:13:06
Oxidado
Not fully understood, but it’s believed that there’s circulation in the blood that gets into the brain and activates the the the gene for BDNF to make more of it, to make more of the protein.
00:13:07 – 00:13:10
Oxidado
A search is underway now to try to find what those circulating
00:13:10 – 00:13:14
Gerald
Including in your lab, right? You this is likely you you and others are studying.
00:13:14 – 00:13:16
Oxidado
Trying to find out what it is.
00:13:16 – 00:13:24
Gerald
You want BDNF in a pill, right? Someday or at least to support our BDNF axis, you know, for the brain function.
00:13:24 – 00:13:36
Oxidado
I think fundamentally the more you understand mechanistically about how to make cells function in a healthy well way, the better tools you have to facilitate that.
00:13:36 – 00:13:44
Gerald
Very cool. This is very encouraging that there’s a real molecular pathway between exercise and cognitive brain health that that connects through neurogenesis.
00:13:45 – 00:14:22
Gerald
So there’s this this other molecule that’s been, I think, kind of in the news a lot lately, very recently, called GPLD1. Again, we don’t want to get too technical. I’m not even going to say what that stands for because it’s kind of a a long name, but but my understanding about GPLD1 is is that it also goes up in exercise, but it’s actually made in the liver, not in the brain. So, when you exercise, there’s some signaling that goes to the liver. GPLD1 goes up and then GPLD1, it’s not clear if it connects all the way to neurogenesis, but it helps protect the blood vessels and what’s called the blood brain barrier. Again, without getting too technical, what’s that story?
00:14:22 – 00:14:49
Oxidado
Yeah I mean it’s pretty interesting and what I’ll just say in a global sense, what it tells us immediately and what we’ve known for a while is that the brain is connected to the rest of the body and the rest of the body affects the brain as well. It’s all one. It’s all one system. So, here we have a protein being made in the liver, gets into the bloodstream, circulates into the blood and and binds to proteins or receptors on the inside of the blood wall.
00:14:49 – 00:14:51
Gerald
On the blood wall in the brain.
00:14:51 – 00:15:04
Oxidado
Yeah. The blood vessels go through. This protein goes in there, binds to some protein,
some receptors on the inside. That activation does something that we don’t know yet. But among them is to increase neurogenesis.
00:15:04 – 00:15:06
Gerald
Oh, it does increase neurogenesis.
00:15:06 – 00:15:08
Oxidado
That was a discovery was made five years ago.
00:15:08 – 00:15:09
Gerald
De acuerdo.
00:15:10 – 00:15:10
Oxidado
And
00:15:10 – 00:15:12
Gerald
Because it’s made
00:15:12 – 00:15:12
Oxidado
Well, we don’t know
00:15:12 – 00:15:14
Gerald
We don’t know how it does that.
00:15:14 – 00:15:25
Oxidado
We don’t know that. And I’ll just be very speculative at this point and maybe this is maybe one of its ways is through this activation of the BDNF.
00:15:25 – 00:15:28
Gerald
Oh, these two could actually they could be connected
00:15:28 – 00:15:37
Oxidado
Because this this might be the factor that that stimulates the BDNF to upregulate it. There’s not good evidence for that, but I’m just trying to give you a feel for how you how do you think about this?
00:15:37 – 00:15:53
Gerald
So this this term, you know, blood brain barrier, am I correct in saying that this isn’t a wall? There’s not like a membrane. Well, there is kind of a membrane, but there’s not like a hard wall. Essentially, the blood brain barrier is the interface between these blood vessels and the cells of the brain. Is that the right way to think about it?
00:15:53 – 00:16:05
Oxidado
And the purpose is the brain is so important in terms of its function, is we want to filter out any toxins that may be in our blood and not let them get into the brain.
00:16:05 – 00:16:06
Gerald
Right. Right. We protect our brain.
00:16:06 – 00:16:07
Oxidado
We protect our brain by building
00:16:07 – 00:16:08
Gerald
Weird stuff in the world.
00:16:08 – 00:16:15
Oxidado
It’s a filter. Think of it as a filter. So molecules only of a certain size or a certain structure can get in and the rest of them are filtered out.
00:16:15 – 00:16:17
Gerald
Okay. I’m glad we have that.
00:16:17 – 00:16:24
Oxidado
So you can imagine that with age if the blood brain barrier begins to break down then you’re going to start getting toxins.
00:16:24 – 00:16:27
Gerald
You could let toxic molecules into your brain and then that could
00:16:27 – 00:16:34
Oxidado
Another reason why you want to retain the strength of that blood brain barrier and this molecule we’ve been talking about.
00:16:34 – 00:16:39
Gerald
Exercise can strengthen your blood brain barrier, which protects you from some of the nasty molecules in the world.
00:16:39 – 00:16:40
Oxidado
That’s right.
00:16:40 – 00:17:43
Gerald
Yeah. I mean a really cool thing about being humans is we can eat almost anything. It’s just amazing how broad our tolerance is for food. And we will be talking with a Salk faculty member, Jamie Blum, who studies that. But the brain needs special protection. So let’s come back to exercise a bit. So as you know, at Salk, there’s these kind of general statements one can make. Exercise is good for you, but at Salk and in your lab, we like to think about mechanism, like why is it and we just gave you just gave two very nice examples. Why is it that this particular healthy behavior whether it’s exercise or good sleep or diet, why is it that it helps brain health? What’s the mechanism behind that, right so because if we can understand the mechanism we can we can better tell people exactly what to do and maybe think about drug discovery opportunities. So what do you see coming next, you know, over the next five years plus, five to 10 years in the mechanistic understanding of the relationship
between exercise and brain health?
00:17:43 – 00:18:06
Oxidado
Yeah. I think we here at the Salk really have this sense that it’s important for us to understand the mechanisms, the molecular and really the the details of how things work. And this question that you’re asking right now is at the core of many things that we care about. And we care about it, as you said, in people and in individuals. We care about it at the individual level.
00:18:06 – 00:18:07
Gerald
De acuerdo.
00:18:07 – 00:18:16
Oxidado
And so I want to know about how your brain, based on your activities and what you’re doing.
00:18:16 – 00:18:19
Gerald
I’m not going to give you a sample though. I mean how are you going to do this at the individual level?
00:18:19 – 00:18:20
Oxidado
This is quite remarkable.
00:18:20 – 00:18:20
Gerald
De acuerdo.
00:18:21 – 00:18:23
Oxidado
We can take a skin biopsy from you right now.
00:18:23 – 00:18:26
Gerald
I’ll give you skin, but I’m not going to give you a piece of my brain.
00:18:26 – 00:18:36
Oxidado
But I can turn that skin directly into a neuron that is that is very similar to the neurons that are functioning in your brain at this point.
00:18:36 – 00:18:36
Gerald
De acuerdo.
00:18:36 – 00:18:46
Oxidado
Then then I can wait months or after you have a exercise experience, training for six months,
I can take another biopsy from you
00:18:46 – 00:18:48
Gerald
and see how I’m progressing or regressing.
00:18:48 – 00:19:01
Oxidado
In your brain, and we can look at the molecular changes that occur, any reprogramming of things that have happened in the cells and it’s not just the neurons. We’ll look at the other cells as well.
00:19:01 – 00:19:02
Gerald
The other cells that are helping the neurons in the brain.
00:19:02 – 00:19:15
Oxidado
I think we here at the Salk have a variety of investigators looking at other brain cells, not just neurons, but glial cells, astrocytes, cells, you know, parasites. There’s there’s so much of these.
00:19:15 – 00:19:28
Gerald
I mean, this sounds like alchemy. I mean, this sounds so it sounds like more than alchemy.
Alchemy is, you know, lead into gold. You’re taking skin and turning it into neurons that
aren’t any old neurons. They’re tightly analogous to the neurons that are actually in my brain.
00:19:28 – 00:19:29
Oxidado
That’s right.
00:19:29 – 00:19:35
Gerald
And as the neurons in my brain change, the neurons that you can make from my skin
samples change accordingly.
00:19:35 – 00:19:42
Oxidado
Yeah. And this is, you know, this is new. This is new work that’s been underway just in the last four or five years.
00:19:42 – 00:19:42
Gerald
De acuerdo.
00:19:43 – 00:19:45
Oxidado
So, it’s a a recent discovery here.
00:19:45 – 00:19:50
Gerald
I mean, what’s the magic? How do you turn like skin cells into neurons? You know, that are my neurons.
00:19:50 – 00:20:00
Oxidado
Think about think about it this way. You have a skin cell in a dish and it has its nature, its
identity of who it is, right? And this is genetic underpinninging of who it is.
00:20:00 – 00:20:00
Gerald
De acuerdo.
00:20:01 – 00:20:39
Oxidado
What we do is we introduce molecules to it which open up the possibilities. We we call them the transcription sites in these cells and then we provide a special set of molecules to those open sites and that turns them into another cell. We’ve had to work on it to figure out what molecules they are. And it’s a process that’s really expanding throughout the world now. So a lot of people in the labs throughout the world are are coming up with new recipes for making cells, dopamine neurons or or certain neurons. So it’s an emerging…
00:20:39 – 00:20:49
Gerald
So I guess it isn’t like outcome. It’s more like you’re changing the clothes of the cell, but it’s still like has its genetic identity and now it’s got the clothes of a neuron rather than the clothes of a skin cell.
00:20:49 – 00:21:09
Oxidado
But let me say this about basic science. We stand on the shoulders of all the giants in developmental biology who defined the molecular pathways of how the cell during development, how a neuron gets made in the first place. And we use those same chemicals to switch the cells over from one fate to another.
00:21:09 – 00:21:17
Gerald
But those developmental biologists, I can’t think that they imagined you could actually just hop from one mature cell type to another. You had to come up the development pathway.
00:21:17 – 00:21:23
Oxidado
I’ve read about this. We’ve all read and written about this and how much did they really anticipate this and there were some,
00:21:23 – 00:21:34
Gerald
imagine this not as science fiction writers, because it’s pretty close to science fiction. My understanding is you are actually taking skin samples from patients.
00:21:34 – 00:21:40
Oxidado
We take them from healthy individuals, from young individuals, from old individuals, and diseased individuals.
00:21:40 – 00:21:42
Gerald
Disease meaning people that have cognitive decline.
00:21:42 – 00:21:43
Oxidado
It’s cognitive decline
00:21:43 – 00:21:44
Gerald
versus people that don’t have cognitive decline.
00:21:44 – 00:21:57
Oxidado
Exactly. And another population that we’re particularly interested in are resilient patients. These are people that are 100 years and older that are cognitively normal within the range, and I want to know why that is.
00:21:57 – 00:21:57
Gerald
What’s their magic?
00:21:57 – 00:22:04
Oxidado
What’s their magic? That’s as important as as seeing what’s not right and cognitively impaired. So yeah,
00:22:05 – 00:22:06
Gerald
Fantastic.
00:22:06 – 00:22:08
Oxidado
It’s a great area of investment.
00:22:08 – 00:22:18
Gerald
Good luck. This sounds like it’s absolutely on the mark for trying to understand how to maintain cognitive brain health through life is to understand how it happens or doesn’t happen and then and then drill in.
00:22:18 – 00:22:41
Oxidado
I’m particularly excited about what we call these longitudinal studies where we take a set of individuals and put them through, sample them before the trial, and then have them go through exercise or some sort of series of experiences and then capture them at a later time point and see if we can really understand the mechanism of how
00:22:41 – 00:23:32
Gerald
Sign me up. You can take some skin. Start now before it’s too late. I want to know how I’m doing. So, another kind of trademark of how we do science here at Salk is that we’re very cross-disciplinary, right? So there are no departments here at Salk. All of the the the scientists here at Salk are kind of in the mix together. And we share ideas across expertise. I think particularly for the issue of brain health, you know, we could talk about exercise as we’re doing today, but but say a bit how exercise connects to all these other things that matter for brain health, like metabolic health, like well, you talked a bit about cardiovascular health, delivering the the supplies to the brain, like immune health, sleep, social health, good social interactions and so on. How do you see these other pieces connecting with with just the exercise part?
00:23:32 – 00:24:24
Oxidado
Yeah, it goes in two directions. So let’s just think about it this way. I’ve been telling you how important it is that when you exercise you’re going to increase your heart rate because you’re going to be breathing more. You’re going to getting the blood circulating more and so the the periphery is going to be accessing the brain directly but the brain is also having an impact on these organs. So there’s feedback from the brain to the rest of the organs. The acute phase is amplified by not just the heart but also you, you’ve said it yourself, the liver. Where is this molecule coming from? The liver and many organs are going to benefit from the exercise themselves. They will benefit by increasing their mitochondria, their energy sources. And if they can be conditioned, their impact on the brain will be improved. Does that make sense?
00:24:24 – 00:24:34
Gerald
Yeah, it does. So the body of course is is feeding, talking to the brain. The brain talks back to the body and within the body. By the body we mean outside the brain. Those parts are talking to each other and it’s all in the gamish.
00:24:34 – 00:24:46
Oxidado
Right. And you need the external sources of nutrition and energy sources. And you want your you want your heart working well, you want your liver working well, so your brain will work better.
00:24:46 – 00:25:17
Gerald
Very good. Okay. Well that’s the brain health in a nutshell. All these things connect and so we want all these good habits. So let’s let’s drill back,onto exercise. So I’m not asking you for medical advice. But as a subject matter expert, what’s your recommendation? What should people do to you know with regard to exercise to maintain cognitive brain health? And we hear all different things. It’s like you know you should do aerobics, you should do strength training, you should do agility training. What’s the recommendation, Professor Gage?
00:25:17 – 00:25:47
Oxidado
Right. Not just my recommendation but the emerging consensus among experts is that you really
need to have a balanced plan. There needs to be, as I said, you need to do stretching exercise to keep limber because for one thing, if you’re doing exercise you don’t want to get hurt, then you won’t be able so you want to do things in moderation, especially at the beginning. But stretching, breathing exercises are wonderful.
00:25:47 – 00:25:48
Gerald
Breathing exercise?
00:25:48 – 00:26:17
Oxidado
Breathing just oxygen so important to feeding these mitochondria and making them work they’re dependent on oxygen for doing it. So getting deep breaths getting lots of oxygen. Eating right is just absolutely important, but stretching exercise, balancing exercise, just simply balancing as well as aerobic exercise like running. It should be a all of them and not picking one versus the other.
00:26:17 – 00:26:17
Gerald
Interesting.
00:26:18 – 00:26:21
Oxidado
But but I call it a balanced portfolio of exercise.
00:26:21 – 00:26:47
Gerald
Balanced portfolio. Your investment in your brain health is a balanced portfolio. Okay. A little stock, a little bonds and Yeah. Because I think many people have a set exercise pattern and they think I’m doing my exercise whether it’s you know a treadmill or a rowing machine or you know yoga and all these are good things but what I’m hearing from you is it’s better to mix up the portfolio than to just do one thing again and again.
00:26:47 – 00:26:51
Oxidado
Yeah. And it’s also more fun and it’s more interesting. It’s more interesting.
00:26:51 – 00:26:54
Gerald
Nothing more boring to me than than running.
00:26:54 – 00:27:10
Oxidado
So before you know for a long time period that gets really boring. So split it up. But that’s that’s the cognitive part of it. But it’s also better for you to do these, you know, balancing exercises are not going to wear you out, but they’re so important, especially as we age.
00:27:10 – 00:27:16
Gerald
Okay. Mix it up and don’t just be a Sunday morning exerciser. It’s something we really want to do because you said that before.
00:27:16 – 00:27:27
Oxidado
I couldn’t say that enough. And that is that you really need to find a regime, find a system that works for you, but do it on a consistent basis.
00:27:27 – 00:27:27
Gerald
Okay?
00:27:27 – 00:27:34
Gerald
For a long time, not just periodically. And that what that means is don’t do too much at any one time
00:27:34 – 00:27:35
Gerald
because you don’t want to hurt yourself.
00:27:35 – 00:27:40
Oxidado
You don’t want to hurt yourself and you don’t want to sort of fall off because you set your bar too high at the beginning.
00:27:40 – 00:27:52
Gerald
So what happens if you can’t do it? What if what if you’ve had injury or you know, you you just have lost mobility? You just can’t exercise. What do we what do we say to those people?
00:27:52 – 00:28:44
Oxidado
Yeah. No, so we we think about this actually a lot and I talked to other experts about this. There are ways in the hospital, even if people are in bed, they can do some isometric exercises, some low impact exercises. They do help a little bit. I think the future, if you want my thoughts about what’s coming next, the goal is to target specific molecules that affect specific cells in the brain so that in a case where person cannot exercise we would be able to pharmacologically manipulate those areas of the brain or the body which will enhance in a similar way to what you would have had as exercise. People called it exercise unti.
00:28:44 – 00:28:52
Gerald
So okay to to simulate the molecular effects of exercise with with pharmacology. Yeah. Wow. That’s an amazing possibility.
00:28:44 – 00:29:10
Oxidado
It’s not here now. Yeah. But but there’s a lot of people out there that are working on this diligently in laboratories. We are, others are too. This is one of the benefits of basic research is that you understand something well enough that you can target very specifically.
00:29:10 – 00:29:28
Gerald
Yeah. Well said. And we want to do this for real. There is a lot of, as you know, junk science out there. Sort of in the pseudocience community, that do this, do that, take this supplement, and you know, it’s going to, it’s going to do what exercise does for you. We’re not there yet.
00:29:28 – 00:29:29
Oxidado
We’re not there.
00:29:29 – 00:29:45
Gerald
Okay. Okay. So, for now, find your way to do a balanced exercise routine. If you’re limited, then you can still do isometric and other kinds of things. And then you know, but the day will come when maybe you’ll still be able to do a lot of physical exercise, but you’ll also have the benefit of
00:29:45 – 00:29:48
Oxidado
and be able to amplify it and and build on it.
00:29:48 – 00:30:55
Gerald
Yeah. Wild. Okay, Rusty, thank you. Fascinating conversation. Thanks for sharing all of your
expertise with our audience and on the importance of the relationship between exercise and cognitive brain health. This is what we’re focusing on this year. All the different things that we can do, the healthy behaviors we can do, exercise being one very powerful example through our our lifespan to improve our health span. Because as you heard, we want to think about the mechanism behind these good behaviors. We want to provide guidance, to all of you so that you do these things. Nothing’s more important than maintaining us, what is actually inside our brain, our cognition. So I think this is really an important series that we’ve been putting together this year. So stay tuned. There’ll be additional podcasts in this series. If you’d like to learn more you can go to salk.edu/brainhealth for this and future podcast series, as well as information about all the amazing research that’s going on here at Salk, including in the lab of Professor Rusty Gage. Thank you all for listening.
00:31:00 – 00:31:27
VO Victoria
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