This is like new math material, new history material, new music material, new motor skill material that you're trying to learn. Increases in autonomic arousal that occur as you're trying to so-called encode the information, you're being exposed to that new information, also significantly improve learning. And it's always through increases in arousal. In other words, whether or not you're measuring cortisol, adrenaline, heart rate, blood pressure, galvanic skin response, how wide someone's pupils are, or small someone's pupils are, or any combination of those things, or any other measures of autonomic arousal, the consistent takeaway is increases in arousal during or after, in particular after, trying to learn a certain material is going to improve significantly the amount of material that one learns, the details of that material, and the persistence of that learning over time. I'd like to take a quick break and acknowledge our sponsor, AG1. 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If you would like to try David, you can go to davidprotein.com/Huberman. Again, the link is davidprotein.com/Huberman. Okay. So now we've established the elevated levels of autonomic arousal either during or after, and indeed also before a bout of learning, the so-called encoding phase of learning when we're exposed to the new material that we want to learn and remember, are all beneficial. This is wonderful news. When we look out on the whole of the literature, on the relationship between exercise and brain health and performance, we see studies that incorporate exercise either before or after about of learning. And we also find studies, believe it or not, that combine exercise with learning in real time, literally exposing people to new material that they're expected to learn or trying to learn while they're walking on a treadmill or running on a treadmill or cycling or rowing. Yes, those studies have also been done. Although for practical reasons, they're not as numerous as the studies exploring the relationship between exercise and learning where the exercise is done before or after the bout of learning. Okay. So what this means is wonderful. What this means is that if you want to use exercise, not just for enhancing your bodily health, but also for brain health and performance, you can do that exercise before, during, or after bouts of learning. That allows you to look at the constraints of your life. For instance, are you one of these people that can get up at five or six or 7 a.m. and exercise before everyone else gets up or before your workday starts or your school day starts, do a round of exercise and then get into your bouts of learning, whatever that material may be. Or are you somebody who has to dive into the workday, school day, family obligations, et cetera, in which case you might only be able to exercise later in the day, but you're probably still somebody who would like to enhance their brain health and performance. So in that case, you might organize the thing that you're trying to learn, the encoding or the exposure to the thing that you're trying to learn, either in written forms, you're reading, or you're listening to it, or you're attending a class or classes, and then exercising after you're exposed to that material in order to get that elevated levels of arousal, not unlike the arrangement of the studies that I was talking about earlier, which used the ice exposure in order to generate increases in arousal and thereby to improve learning and memory. So in the show note captions for this episode, we've batched a number of different references that have explored the relationship between exercise and cognitive performance. And across those studies and the ones that are referenced therein, you'll find studies where the exercise bout was done before, where the exercise bout was done during, where the exercise bout was done after a round of learning or encoding of information. And I should mention that different studies focus on different cognitive tasks. So exercise and the arousal associated with exercise has been shown to acutely improve recall. So just raw recall of material, the details in material. It's been shown to improve cognitive flexibility through things like the Stroop task. And so in a very convenient way, exercise has been shown to acutely improve performance on all those sorts of brain and memory tasks, which is greatly reassuring to all of us because what it means is that it probably doesn't matter so much when you do your exercise or what it is that you're trying to learn. It's going to be beneficial as long as the thing that you're trying to learn and the exercise are positioned fairly closely in time. the one caveat to that is that several studies have explored the relationship between short duration high intensity interval training and cognitive performance in particular executive function that cognitive prefrontal flexibility that we were talking about a few moments ago and on the whole all of those studies point to improvements in executive control and function. So that context-dependent switching of knowledge and your ability to think about things in a very agile way, if you will, if people did a high-intensity interval training session just before they do that bout of cognitive flexibility learning. However, several studies have also looked at the effect of repeated bouts of high-intensity interval training. And in some cases, looking at the mechanisms by which high-intensity interval training improve cognitive performance. And the basic takeaway is the following. And again, I'll provide references to these in the show note captions. That high-intensity interval training done before, or believe it or not, even during cognitive flexibility tasks, a couple of studies have actually explored that, significantly improves performance on those tasks. Again, we believe this is likely through enhanced levels of arousal, although some data also point to the fact that it's also likely through enhanced cerebral blood flow, simply more blood being delivered to the brain during or in particular after high intensity interval training. More blood, more fuel, and other molecules being delivered to the brain during a cognitive task or cognitive flexibility task, makes sense why that would improve cognitive function. And yet, when studies have explored the consequence of doing multiple high intensity interval training sessions, and when I say high intensity, I mean high intensity. These are studies where lactate is elevated. We'll talk more about lactate in a few minutes, where typically people's heart rate is either close to or at their maximum heart rate for some period of time, either 30 seconds, 60 seconds, two minutes, or in some cases, people are pushing really, really hard for four minutes, then resting for four minutes, then pushing really hard for four minutes, then resting for four minutes, four times over the so-called four by four program that I know a number of you have heard about. If you haven't, it's very intense. So you can imagine all out for four minutes, then rest, all out for four minutes, then rest. Doing that several times in a day, okay? So two bouts of four by four or two high intensity interval training sessions of any kind has been to diminish cognitive performance if the cognitive task comes after the second high intensity interval training session. Now, for most of us, including me, that makes sense. You think, well, they're tired. You know, people aren't able to focus as much because they're devoting all this energy to the exercise. And indeed, that's true, although the mechanism is interesting. The studies that have looked at this have actually found that cerebral blood flow during the two bouts of high intensity interval training are more or less equal. So it's not that the first session necessarily precludes high performance in the high intensity interval training session in the second session, but then when you go on to try and do a cognitive task that's demanding and also requires elevated levels of cerebral blood flow, you find that performance drops. And this is correlated with reductions in cerebral blood flow that come from doing too much high-intensity interval training. Now, I have to acknowledge that most people aren't doing multiple high-intensity interval training sessions per day. But this is a reminder, an important reminder in fact, that if you're using exercise to try and improve brain health and function, or even if you're just somebody who's exercising but is also expected to use their brain to learn things throughout the day as most of us are, and to attend to things throughout the day, you need to be cautious about not overdoing the high intensity interval training sessions. This is also true for resistance training. You need to be aware that very high intensity exercise, yes, increases cerebral blood flow, and the delivery of all these fuels and other compounds to your brain during the exercise. If you do that correctly and you don't overdo it, you can capture some of that wave of blood flow, fuel, et cetera, as you enter the learning session. But if you quote unquote overdo it, then you're going to arrive to that bout of learning with reduced cerebral blood flow, and you're going to be in a state that it's very difficult to focus and learn new information. So there is such a thing as too much arousal from exercise that leads to troughs in arousal that diminish cognitive performance and learning. Now, all of this is focused, of course, on the relationship between exercise and brain function at the acute level, the immediate level. It's fair to say that all high-intensity exercise and resistance training is going to support brain function in the chronic sense, in the long-term sense. In fact, the literature points to that. And once again, I've batched the references for this episode so that they're grouped together according to the specific topics and timestamps. And the two studies that I recommend you look at if you're interested in this relationship between high intensity training and cognitive function, in particular executive function, that cognitive flexibility I was talking about earlier, such as in the Stroop task, there's a wonderful article entitled Executive Function After Exhaustive Exercise. That's one to look at. And the other one, which I think is really nice, and therefore I've placed there, really points to the way that a single bout of exercise can acutely improve brain function, in particular executive function. And the title of that paper, not surprisingly, is a single bout of resistance exercise can enhance episodic memory performance. Here's a fun one. As I continue to hammer on this thesis that so many of the positive effects of exercise on brain health and performance, at least in the acute sense, immediately after the exercise, some cases during the exercise, are due to arousal. Well, then it should make sense why things like so-called exercise snacks, this idea that throughout the day, you suddenly do 25 quick jumping jacks, or you jump up and down five times, or you do 20 air squats. We've heard about exercise snacks in different contexts, such as adjusting blood glucose levels. You hear a lot about that. After meals, take a walk, or do some jumping jacks really quick, or do 20 air squats throughout the day. And people talk about the sort of outsized positive effects of those. Well, check this out. When it comes to high intensity interval training and positive effects on cognitive performance, there's a study entitled, the influence of acute sprint interval training on cognitive performance in healthy younger adults. And this study has people do six second all out efforts. You heard that right, six seconds. Okay. So six, six seconds, it always is tricky. They always use the same numbers, the, you know, four by four by four, okay. Six, yes, the number six, six second all out efforts, sprinting on basically a stationary bike, and then a period of rest of one minute between those six second all out efforts. And they see a significant improvement in cognitive performance. So yes, it's true that you can do very brief, very intense bouts of exercise. I mean, just think about six seconds of sprinting, one minute of just cruise or rest, six seconds, and then just repeat for six sprints total of six seconds each, and experience an enhancement that is an acute or immediate enhancement in cognitive function. And I can imagine no other mechanistic explanation for that aside from increased levels of autonomic arousal. Any other mechanism that you could envision, you know, IGF-1, irisyn, BDNF, things that we'll talk about in a few minutes, yes, those might be deployed as well, but in terms of seeing something so brief, having such a fast action on cognitive performance, and given what you now know about the relationship between arousal, focus, and cognitive performance, I'd be willing to stake, let's say six of my 10 fingers on the idea that it's all due to enhanced autonomic arousal. Okay, let's talk for a few minutes about the mechanisms by which exercise improves brain health and performance. And I realized when I say mechanisms, some of you may say, okay, well, I just want to know what to do. I don't need to hear about the mechanisms, but in this case, understanding just a little bit about the pathways by which exercise impacts the brain can give you a ton of leverage in designing the best exercise schedule for your brain health and performance, and frankly, for your exercise schedule generally to generate things like fat loss, improvements in strength, hypertrophy, endurance, and so on. In fact, let's do this mental experiment together. If we were to ask ourselves, how is it that exercise improves brain health and performance? Based on what you know now, you'd probably say, well, it increases arousal, the catecholamine, so dopamine, epinephrine, norepinephrine. It probably increases heart rate, so more blood pumping to the brain, and so on and so forth. And you would be correct about all of that. But let's just think a little bit more deeply about how exercise actually impacts the brain in the short and long-term and ask ourselves, what are the different physical pathways? What are the different chemical pathways by which the movement of our body changes the way that our brain works in the short and long-term? So if we were to draw a stick figure of a human and orient ourselves to the different locations or organs in the body that contain potential sources of information for the brain, one place that we could start would be of course the heart. When you do cardiovascular exercise of any kind, intense or not so intense, short or long, your heart rate increases, your blood pressure increases. Likewise, if you do resistance training, there will be heart rate increases. Those heart rate increases will come down between sets, but your heart rate tends to increase when you exercise. That's sort of a duh. Well, when your heart rate increases, there's actually both increased blood flow to the brain and the delivery of all the things that that blood carries, but there are also neural pathways that carry signals about that heart rate, about those blood pressure changes to the brain in order to increase our levels of alertness and focus that we can leverage toward learning. So the first location in the body that we know can communicate with the brain is the heart. When our heart beats faster, that's communicated to our autonomic nervous system, which resides in a number of different brain areas. In fact, it's a network of brain areas that act in concert to create what we call autonomic arousal. We also have another pathway that goes back from the brain to the heart and other organs that we call the vagus nerve, which is a two directional pathway, you know, up from the body to the brain and from the brain back to the body. We're going to talk a lot about the vagus. In fact, let's talk about the vagus now. When we exercise, we release adrenaline, which is also called epinephrine from our adrenal glands, which are small glands that reside atop both of our kidneys. That adrenaline or epinephrine, as it's also called, does many things in our body. It's responsible for increasing our heart rate further. It's responsible for a number of effects on the so-called endothelial cells that make up the vessels and capillaries. And it has impacts on the neurons in our body that create all sorts of changes in the way that blood flows, how fast it flows and so on and so forth. Now, here's a key thing to understand. Adrenaline, epinephrine does not cross the blood brain barrier. So the adrenaline from our adrenals doesn't actually get into the brain to stimulate elevated levels of alertness. Rather, it acts on receptors on the vagus nerve. Again, the vagus nerve communicates with the brain and also in the vagus nerve, certain brain areas communicate with the body. So adrenaline has a lot of effects within the body, but when it's released, it also acts on so-called adrenergic receptors on the vagus nerve. then the vagus nerve is activated in a way that stimulates the activity of a brain area, because remember, the vagus goes from the body into the brain, stimulates the so-called NST, and because neuroanatomists like to argue about naming, sometimes it'll also be called the NTS, the nucleus of the solitary tract, or the nucleus tractus solitaris, super annoying, I know. Forget the acronym unless you want to know that it's sometimes NST and sometimes it's NTS. Don't ask me why neuroanatomists do this. In any case, the NST can then communicate with a really important brain area whose name you should remember, which is the locus coeruleus. The locus coeruleus contains neurons that release, among other things, norepinephrine, which is similar in action to epinephrine, but different. Neurons in the locus coeruleus send those little wires that we call axons into the brain in a very widespread manner. It's almost as if they're positioned to sprinkler the brain with a neurochemical, and that neurochemical is norepinephrine. They also have the capacity to release other neurochemicals, but right now we're concentrating on norepinephrine. When norepinephrine is released from the locus coeruleus, it has this tendency to elevate the levels of activity in other brain areas through this sort of sprinkling like mechanism. What that means is that other areas of the brain, such as your prefrontal cortex, such as your hippocampus, such as different areas of the hypothalamus, and indeed lots of brain circuits, all have a greater capacity to be engaged. This is what we're talking about when we talk about autonomic arousal, release of adrenaline from the adrenals that has action within the body, elevated heart rate, blood pressure, etc. And then adrenaline also from the adrenals to the vagus, from the vagus to the NST, NST to locus coeruleus, and then locus coeruleus sprinklers the brain with this norepinephrine, raising the levels of baseline activity in all those brain areas, and making them more likely to be engaged by things that we're trying to attend to, more likely to engage, say, the neurons of the prefrontal cortex that can learn context-dependent strategy switching, such as in a Stroop task, or when we're trying to attend to information and we go, okay, here's something important. I need to pay attention to this. We're able to do that because of that elevated level of norepinephrine. It facilitates, it's permissive for elevating our levels of attention and focus. It's also permissive for our hippocampus to encode new memories and for a bunch of other brain areas to do their thing, so to speak. So knowing these mechanisms is actually worthwhile. If you've ever heard that exercise can give you energy, this is the basis of that statement, right? Many people, in fact, myself for many years thought, okay, I definitely have to sleep well in order to have energy and focus. That's absolutely true. Still true. Will always be true. I should maybe have some caffeine, be hydrated, well-nourished, all this stuff in order to have the energy to exercise. But it's also true that exercise gives us energy and this is how it gives us energy. When we move our body, the adrenals release adrenaline and the adrenaline acts through two different so-called parallel pathways within the body. But again, it doesn't cross the blood-brain barrier. So then there's a series of what we call signaling relays or circuit relays up to the locus coeruleus, and then a sort of analog, it's different, but an analog to epinephrine, norepinephrine is released within the brain. And lo and behold, we have elevated levels of both bodily energy and brain energy and focus that we can devote to that exercise, but also to the learning that comes after that exercise, which explains pretty much everything that we've talked about up until now, during the course of this podcast. So the next time you're feeling a little tired and you don't want to work out, remember, exercise gives you energy through the pathways that I just described. Now, anytime I talk about the adrenals, people start talking about adrenal burnout. They say, oh, you burn out your adrenals. You know, there are these crazy theories that you'll hear out there. You know, coffee burns out your adrenals. Not true. You'll hear that if you exercise too much, it might burn out your energy or your adrenals. Look, you have enough capacity within your adrenals to survive relatively long famines, to survive long bouts of challenge, stress of many, many different kinds, short challenges, and so on. You're not gonna burn out your adrenals. There is something called adrenal insufficiency syndrome, which is a real syndrome. There are diseases of the adrenals, but that's not what we're referring to here. You have plenty of adrenaline in your adrenals that you can deploy through movement, through exercise, to get the elevation and arousal, attention, and so forth that we've been talking about. In fact, there's a set of biological pathways that were just recently discovered that will allow you to understand how to use movement in order to engage your adrenals so that then those adrenals can release adrenaline, impact your vagus, impact the organs of your body, the locus coeruleus, and elevate your levels of attention and focus. And a lot of the core components of these pathways are highlighted in a paper that I absolutely love, another paper I absolutely love. This is from Peter Strick's laboratory at University of Pittsburgh, which is entitled The Mind-Body Problem, Circuits That Link the Cerebral Cortex to the Adrenal Modulla. The adrenal modulla are those adrenals that I've been referring to in the body. And the question that Peter Strick and colleagues asked was how is it that movement actually gets the adrenals to release adrenaline? Like what's the signal? Does it come from the muscles? Does it come from, you know, the skeleton? It's perfectly reasonable to assume that there are signals that come from the muscles and from the skeleton that cause the adrenals to release adrenaline when we exercise. But what Strick and colleagues did was actually super clever. They took some new tools that had just become available. These are tools that allow the tracing of neural circuits from organs in the body all the way back up to the brain or from one brain structure to another brain structure and then to yet another brain structure. We don't have time to go into all the technical details, but this is a technique that perhaps I'll talk about on a future podcast. It's one that my laboratory used for a number of years to trace other neural pathways. What they discovered is that there are essentially three categories of brain areas, all of which communicate with the adrenals and can cause them to release adrenaline to create this elevation and arousal and attention. Those three brain areas include areas of the brain that are involved in thinking, what we call cognition, areas of the brain that are related to what are called affective states, which is just kind of a more general category that includes emotions. Okay, if you saw the Huberman Lab podcast episode that I did with Lisa Feldman Barrett, she explains beautifully the distinction between affective states and emotions. But these are brain areas that basically relate to what we are feeling or how we're perceiving our environment and how we're reacting to it, these sorts of things. And then there's a third category of brain areas that most robustly communicates with the adrenals. And these are a collection of brain areas that are all involved with movement of particular areas of our body. These areas are broadly referred to as the motor network. So these are areas of the so-called cerebral cortex, which are on the outer portion of the brain. And they send these wires down the spinal cord. There's a little relay in the spinal cord called the IML. If you're interested in the anatomical details, I'll put the link to this paper in the show note captions. In any case, these brain areas that are involved in motor movement, send axons, those wires, down to the spinal cord, then from the spinal cord, they send a relay out via what's called the cholinergic preganglionic neurons. Basically what ends up happening is that acetylcholine, which is a neuromodulator, is released from these neurons that originate in the spinal cord onto the adrenal medulla. And then the adrenal medulla, the so-called adrenals, same thing, adrenal medulla, adrenals, releases adrenaline. That creates these effects in the body on the heart, the muscles, and other tissues. And then as described before, that adrenaline also acts on the vagus, the vagus up to the NST, the locus coeruleus, and we have this elevation and alertness. So this paper and papers that came subsequent to it really explain how it is that the movement of our body, AKA exercise, allows us to have this elevation in arousal and alertness. It's a loop, okay? The adrenals release adrenaline. They do these things by these two parallel pathways I've been talking about, but your decision to engage these motor areas, to move particular areas of your body, is what deploys that adrenaline. Now you might be thinking, well, duh, okay? When I exercise, there's adrenaline release. In order to exercise, I need to move my body, and these brain areas control the movement of my body. But it's not a duh, it's actually very profound because it turns out that the specific brain areas that best activate the adrenals are the brain areas that control the muscles closest to the midline, the core musculature and the brain areas that are involved in generating the sorts of movements that we would call compound movements, at least in the context of resistance training, or that are responsible for moving multiple joints at the same time. So what this means in the practical sense is if you are feeling sluggish, you want energy, or you're simply exercising both for bodily effects and brain effects, you need the deployment of adrenaline, of epinephrine. You need the deployment of norepinephrine in the brain. And by the way, anytime you have a deployment of norepinephrine in the brain, almost always, there's a coordinated action of release of dopamine, which most people have heard of by now. Dopamine is involved in motivation as well as movement, et cetera. So the simple takeaway here is if you want to get the arousal that comes from exercise in order to use that arousal, to leverage it towards better cognition, brain health, et cetera, the key thing is to make sure that you're doing exercises that are compound exercises. So that these would be the movements, you can look these up, just say compound exercises, you can put that anywhere and you'll see that that includes things like squats, deadlifts, bench presses, dips, pull-ups, rows. And yes, of course you want to train your whole body so that you have symmetry of a function of strength and you want to offset any injuries and things of that sort, or aesthetic reasons perhaps. But the idea here is if you want energy from exercise, you want focus, you need the deployment of the neurochemicals that we've been discussing, most notably epinephrine and norepinephrine. And through the identification of this motor network, as well as the effective and cognitive networks that converge on this area of the spinal cord and then send communication to the adrenal medulla, you can essentially control the levels of arousal that your body and brain produces. So in describing this, my hope is that you'll no longer think about exercise as just elevating your heart rate, or you no longer think about exercise just as moving your body, but rather that the movement of your body is creating specific neurochemical outcomes, both in the body and the brain that create the arousal, that initiates the improvements in focus and attention that allow you to learn better, and that contribute generally to brain health and longevity. And of course, you aficionados out there will remind me, I'm sure, but I'm going to beat you to the punch here. Yes, your hypothalamus is also talking to your pituitary, which releases certain chemicals into your bloodstream, which also go to your adrenals to cause your adrenals to deploy both adrenaline, epinephrine, as well as cortisol. That pathway is still intact, okay? But that's a slightly slower pathway. Here I'm focusing on the neural pathways, some of which have only recently been discovered in the last five or 10 years, that work very, very fast to generate the sorts of arousal that are relevant to brain function and brain longevity. Okay, nothing has changed in terms of the old story about how the brain impacts the adrenals. That's all still there. But here we're into the modern stuff. And by the way, for those of you that are interested in things like psychosomatic disorders, trauma, and how trauma can quote-unquote be stored in the body, and not so much stored in the body, but how it can impact the body and then how the body itself can impact the brain. This paper has also been used as support for the idea that indeed those affective areas, those emotional areas, those cognitive areas have a route by which they can communicate with the adrenal medulla to cause the release of adrenaline when we have specific thoughts. It was always known that if we have specific thoughts, it can quote unquote, stress us out, our heart rate can go up, et cetera. This paper also provides a reasonable anatomical substrate for that phenomenon. You know, I never want to make too much of any one single paper or finding, but I will say that after I read that paper from Strick and colleagues and through some of the subsequent discussions about that paper that I overheard at meetings and so forth, it really made me think differently about exercise. And now anytime that I'm feeling tired, provided that I'm not chronically sleep deprived or something of that sort, I remind myself that if I start moving my body, in particular, if I engage core muscles, that was one of the key findings in that paper, that the areas of the brain that control the core muscles, as well as do compound movements. I move multiple joints. I start, you know, warming up in a way that includes some, you know, maybe even just air squats or some running in place or jumping jacks, things of that sort, that the increase in energy that I'm perceiving is real. It's based on the same neurochemical outputs that would occur had I gone into the gym or to the run or whatever workout with tons of energy, it would just have increased the level of adrenaline further. So this idea that we can actually control our body with our mind, and to some extent, our mind with our body, that's absolutely true. And this is one of the tools that I find particularly useful anytime I want to overcome that wall of resistance to not doing the physical exercise that I know I and basically all of us should be doing. I'd like to take a quick break and thank one of our sponsors, Function. I recently became a Function member after searching for the most comprehensive approach to lab testing. While I've long been a fan of blood testing, I really wanted to find a more in-depth program for analyzing blood, urine, and saliva to get a full picture of my heart health, my hormone status, my immune system regulation, my metabolic function, my vitamin and mineral status, and other critical areas of my overall health and vitality. Function not only provides testing of over 100 biomarkers key to physical and mental health, but it also analyzes these results and provides insights from top doctors on your results. For example, in one of my first tests with Function, I learned that I had two high levels of mercury in my blood. This was totally surprising to me. I had no idea prior to taking the test. Function not only helped me detect this, but offered medical doctor-informed insights on how to best reduce those mercury levels, which included limiting my tuna consumption, because I had been eating a lot of tuna, while also making an effort to eat more leafy greens and supplementing with NAC, N-acetylcysteine, both of which can support glutathione production and detoxification and worked to reduce my mercury levels. Comprehensive lab testing like this is so important for health, and while I've been doing it for years, I've always found it to be overly complicated and expensive. I've been so impressed by Function, both at the level of ease of use, that is getting the tests done, as well as how comprehensive and how actionable the tests are, that I recently joined their advisory board, and I'm thrilled that they're sponsoring the podcast. If you'd like to try Function, go to functionhealth.com/Huberman. Function currently has a wait list of over 250,000 people, but they're offering early access to Huberman Lab listeners. Again, that's functionhealth.com/Huberman to get early access to Function. Okay, so let's think just a little bit more about how the body communicates with the brain during exercise, both in order to understand the mechanisms by which exercise improves brain health and function, but also ways that we can leverage that to improve brain health and function by using exercise. One of the more interesting and powerful and indeed surprising ways that the body communicates with the brain during exercise to improve brain health, and indeed our ability to remember things and to learn, is the way that our our skeleton, when they're under loads, okay, when they experience mechanical stress, not severe mechanical stress that would break them, but mechanical stress, they release hormones, in particular, something called osteocalcin. Now, you might be thinking, wait, the bones release hormones? Yes, your bones release hormones, one of which is called osteocalcin. Osteocalcin is an incredible molecule. Animal studies that were done mainly at Columbia School of Medicine, but later also at Columbia and elsewhere in humans have shown that osteocalcin is released from the bones during exercise, both in mice and in humans, travels to the brain so it can cross the blood-brain barrier. And there it can encourage the growth of neurons and their connections within the hippocampus, an area of the brain that's vitally important for the encoding of new memories. And there are some data, not a ton, but there's some data which suggests that perhaps, I want to highlight, underscore, and boldface, perhaps, can increase the number of neurons in the so-called dentate gyrus of the hippocampus to allow even better capacity for memory. Now, osteocalcin is therefore a really interesting molecule, right? Comes from bones, travels to the brain, improves functioning of the hippocampus, which is important for learning and memory. That's amazing. And it does so in part through the actions of something that most of you perhaps have heard of, which is called BDNF, or brain-derived nootrophic factor. Now, it's very important for us to understand that anytime we hear about exercise increases a growth factor, and by the way, exercise increases brain-derived nootrophic factor, it increases growth factors that cause the growth of endothelial cells, so blood vessels, we'll talk more about that in a moment, and it increases nerve growth factors. It's not just BDNF, there are lots of different growth factors, a few of which NGF and BDNF act on neurons and other growth factors that act on endothelial cells, vasculature. It seems that a lot of the effects of BDNF on the brain that are caused by doing exercise and that benefit us in terms of short and long-term memory, our ability to encode new things and remember them for long periods of time, to resist age-related degeneration, because that's the case indeed, that our hippocampus decreases in volume over time as we age, just naturally, even in somebody that doesn't have Alzheimer's dementia, and exercise can adjust the slope of that decline significantly, provided there's enough exercise and the appropriate exercise.