transcript

Speaker 1:
[00:00] He helped to popularize the idea of retirement, essentially by telling people that once you hit 60, you're essentially useless and you need to be put out to pasture. And we have then internalized that as society and we expect significant loss of function. If we think that we're going to lose function with age, we stop doing the things that prevent the processes of aging and therefore it becomes a self-fulfilling prophecy. We have this overarching idea of trying to build what I call Headroom. So Headroom is the maximum capacity that you have available to you. Because when things come in that inhibit or diminish performance, sleep deprivation, acute stress, illness, right? You want more capacity available to you so you can maintain function. How this then works, I have this model that I call the 3S model of brain health. And the 3S is a stimulus supply and support.

Speaker 2:
[00:50] This is just ground zero for the kind of knowledge for having the kind of brain that you want. And the kind of brain you want right now, even if you're 19 years old or if you're 90 years old. You're listening to The Human Upgrade with Dave Asprey. What if you could make your brain sharper in just 10 to 15 minutes a day? Focus comes down to how well your mitochondria are working, because that's how your brain makes energy. When your mitochondria slow down, you get brain fog, fatigue, and low motivation. Light changes how that system behaves. Scientists have been studying near-infrared light for years because of how it interacts with mitochondria and supports energy production in your brain. And that's why I've been using Neuronic. It's a wearable light therapy device for your head that uses near-infrared light to support clarity, focus, and overall brain performance at home without adding another complicated routine. It is simple to use, easy to stick with, and fits into your day in just a few minutes. If you're ready to ditch brain fog, or you just want better mental performance, this is a straightforward tool to add. Go to Neuronic.Online and use code DAVE for $100 off. How many nights have you stared at the ceiling, counting the hours until morning? Maybe you tried a sleep supplement, but it knocked you out and left you groggy, like you traded one problem for another. Poor sleep doesn't just make you tired. It kills your performance, slows your brain down, and speeds up aging. Killswitch from Switch Supplements solves that problem. It works with your biology instead of against it. It contains five gut-friendly, extensively researched ingredients like GABA, magnesium glycinate, and tart cherry extract to help you fall asleep naturally, stay asleep, and wake up clear. And it's in the form of a delicious, sugar-free, no BS hot cocoa drink. Sleep tracking data proves how well it works. People consistently hit 90-plus sleep scores and more than double their REM sleep in only three days with KILLSwitch. If you're ready for the best sleep of your life, order now at switchsupplements.com and use code DAVE for 20% off. If you don't sleep better, you get your money back. KILLSwitch works with your biology. Your body does the rest. This episode of The Human Upgrade is going to be a lot of fun, kind of like all of them, because I wouldn't do this if I wasn't having fun. This is incredible. I get to learn from so many people and share some knowledge with you, and it always makes me happy to do it. So I don't see myself slowing down after 1,400 episodes. Pretty sure I've hit a stride there. Our episode today, Dr. Tommy Wood. He's a neuroscientist. I would just call him an elite level nerd and a performance consultant to world-class athletes. I wanted to have him on because of his forthcoming book, which is called The Stimulated Mind, How to Future-Proof Your Brain from Dementia and Stay Sharp at Any Age. This is stuff, if you've read, let's see, Headstrong, my book, very similar themes in that. Looking at cognitive function and physical performance, they're intimately tied. You say, well, Dave, maybe I'll listen to you. Maybe you're right about some things, but you're an unlicensed biohacker. I'm like, hey man, that means you can't take away my license for telling you the truth, which is real. But Tommy here, well, he has a medical degree from a small community college called the University of Oxford, and a PhD in Physiology and Neuroscience from the University of Oslo, and a professor of Pediatrics and Neuroscience at University of Washington School of Medicine. This is a guy who's gone deep, like really deep on both sides, where the academics happen and on where the performance happens. So I'm really excited to have him on, and like me, he's been on the Joe Rogan show, which is quite the experience. One other area of major interest for me is racing car drivers. Danica Patrick's been on the show a couple of times, a good friend, and we talk about reaction time. I look at something called P300D, which is the lag between when a signal hits your body and when your brain does something about it and gets a signal. And one of the most challenging things for attention is Formula 1 race car driving, because you're going so fast, you have to stay focused, and if you lose focus for a little while, you die. So this is maybe the best crucible there is for focus. How do you make focus happen at 200 miles an hour for an hour?

Speaker 1:
[05:41] There's a few things that go into this, right? And the interesting thing is that reaction time obviously is important for a Formula 1 driver, particularly off the start line. But there's a balance between trying to improve reaction time and trying to improve the performance of a complex skill, because reaction time is a very fundamental aspect of cognitive performance. But when it comes to the factors that influence cognitive performance, it's very basic. So that for more complex skills, you need a balance of arousal, which is what we talk about. So when you think about complex skill performance, and this is based on the original work by Yerkes and Dodson. They did these studies in mice more than 100 years ago, but unlike most mouse studies, and I say that as somebody who does rodent research for a living, unlike most mouse studies, this actually did translate over to humans pretty well. And what they found was that for very simple tasks, more arousal is better. This is like reaction time. So you can just amp somebody up and they'll react faster. But for complex tasks, you can be over aroused. There's like a bell-shaped curve. So for any complex skill, there's an optimal level of arousal. At that optimal level of arousal, that's where flow states are possible, that's where clutch states are possible, that's where you get the best possible performance. If you're under aroused, you're sort of sleepy, detached, not really into it. If you're over aroused, you're anxious, jittery, sweaty. You can't perform your best then. So there were dozens of stories from coaches and drivers where they got themselves too amped up before they got in the car. They took too much caffeine or some other kind of stimulant, and then you shoot off the line, but then you plow into the wall on the first corner when you're trying to navigate the other 20 drivers around you. There's only 21 drivers from this year. So what we really think about is this balance of arousal as we get into the car. So we may have taken a long view before then, thinking about all the different factors that relate to skill acquisition, adaptation to all the things that they're doing, rest and recovery, making sure their nutrition is on point. We've done studies myself looking at processing speed. That's one of the aspects that are going to be critical. We know that relates to nutrient status and other aspects of health status as well as physical performance. But when we get into the moment, it's all about getting the driver in that right balance of arousal where performance is possible. So depending on the individual, this could be, right, we need to increase their arousal. We can use light, we can use cold, we can use exercise, we can use breath work. And sometimes you might use some targeted supplementation or stimulants, depending on what works well for them. And they've done a lot of testing in various scenarios to figure that out. Sometimes we have to bring them down from the top end of the curve, right? Even elite athletes get nervous. So then we might think about similar things, like what are we doing in terms of breath work and other aspects of stimulation? How can we get them to focus in, but in a calm manner with different sort of warm-up drills? So it's really about kind of getting them dialed into that right level of arousal so then they can go out and perform well in the car.

Speaker 2:
[09:06] So it's kind of giving them a slider switch so they can adjust their arousal to just the right level, which could be up or down.

Speaker 1:
[09:13] Absolutely. Yeah.

Speaker 2:
[09:14] And how much of that is pharmacological or supplements versus environmental?

Speaker 1:
[09:21] Again, it will depend a little bit on the driver. A lot of them have sort of tinkered with that. So caffeine use is very common. Some are interested in some of the newer kind of caffeine derivatives or related compounds, paraxanthine, theocrine, or t-crene. Some of them may use creatine before they get in the car because for some people creatine is mildly stimulating. We, like some might use tyrosine, L-theanine to kind of balance some of the caffeine. So some of that stuff is certainly common. But then the rest of it...

Speaker 2:
[09:53] Modafinil? Is that allowed?

Speaker 1:
[09:55] No, because they're drug-tested athletes, so they can't use Modafinil. Unless they had a therapeutic use.

Speaker 2:
[10:00] You need to just be done with that. That whole drug-testing thing is done. They should just let them use stuff that works.

Speaker 1:
[10:06] Well, you know, maybe if they add Formula 1 to the Enhanced Games, we can talk about that. But at least for right now, we have to be very careful about the things that... Right now, we have to be very careful about the things that we use with them for that reason. There is some pharmacological supplementation type stuff, but then the rest of it is all based on what's the routine that works for them. You know, often the motorhomes are very dark, so we might try and find like light boxes and things because we don't want them sort of sleepy and drowsy before they're getting into the car. Sometimes we're using cooling beforehand, particularly in warm environments, but that could be a thing. Breathwork and then other activation drills, you know, balls and that kind of stuff juggling can certainly come into play as well depending on the driver.

Speaker 2:
[10:53] That is so cool. Now, for the rest of us who aren't driving that fast regularly, brain aging is a big deal. So what determines if your brain is going to age well or fall apart as you age?

Speaker 1:
[11:05] The way I think about this is I have, and this is what the sort of the book builds towards, is we have this overarching idea of trying to build what I call headroom. So headroom is the maximum capacity that you have available to you. And I in many respects liken it to physical performance because they are intimately connected and they are definitely related. So headroom from a physical standpoint might be the difference between the strength it takes to get up out of your chair or off the toilet, which is like the leg strength you need just on a day-to-day basis, getting around the house versus like what's the maximum amount you can squat, right? That's your headroom because when things come in that inhibit or diminish performance, sleep deprivation, acute stress, illness, right? You want more capacity available to you so you can maintain function. The brain is essentially the same. That's the strategy and then the tactics that go into headroom are all these different modifiable factors that we know about the environment related to physical training, nutrition, stress management, sleep, social connection, and then cognitive stimulation, which I think is a primary driver of cognitive function. Just like with physical function, the stimulus we apply to tissues is the primary determinant of how they function. And so, how this then works, I have this model that I call the 3S model of brain health. And the 3S is a stimulus supply and support. And again, very similar to like a stimulation recovery adaptation model that you would have for physical training and physical performance. So, the most important thing is the stimulus you're applying to your brain. This is skill learning, social connection, complex motor skills, just learning in general, which we know is a primary driver of how our brains both first develop and then maintain their function long term. Then once you've stimulated some aspects of the brain, or some network in the brain, you get an increase in blood flow to those areas through the process of neurovascular coupling, right? So, then you need good cardiovascular function. So, now we're in the supply S. You also need good metabolic health, because you're going to have to have a supply of some kind of energy substrate. That could be glucose, ketones, lactate, whichever you prefer, depending on the scenario. And you're also going to need a supply of nutrients that kind of form the structure and the different parts of the brain that you're going to use. Vitamin D, omega-3s, B vitamins associated with methylation, etc. Then you've stimulated the brain, you've brought in the necessary components. Then you need some time for the brain to adapt to that stimulus. So this is the support bucket. So we know that sleep is where most of that happens, but also how you use strategic rest periods during the day becomes important as well. Other support factors include neurotrophic factors produced during exercise, hormones are a big part of support for neuroplasticity, so that kind of part of physical and hormonal health. And then you want to avoid things that kind of inhibit that process, chronic stressors, inflammatory conditions, dental disease, excessive alcohol intake, etc. So these three S's in the interact. And that's important because what that means is when you change one thing, everything shifts. So, right, if you're not sleeping well and you start to sleep, then we know that blood pressure improves and blood sugar improves and inflammation levels improve and you feel more social the next day, so you're more likely to interact with people in a social manner. And you're more likely to engage in cognitively stimulating tasks because we avoid those when we're cognitively fatigued or fatigued. So, the reason why I talk about it like that is that you don't necessarily have to start with a list of 50 things you have to fix. If you start to move one thing, like the whole network starts to shift in your favor, and that improves cognitive function today and then decreases the risk of dementia long term.

Speaker 2:
[15:03] You started out that really comprehensive list by talking about stimulation and learning things, skill acquisition. Couldn't you use light or electricity or magnetism to stimulate the brain?

Speaker 1:
[15:18] Yes. Yeah, you can. So, this I think is really interesting. Obviously, the thesis of my book is that stimulating the brain is the primary driver of how it functions, and the most interesting new technologies for supporting long-term cognitive health and as treatments for neurodegenerative disorders are stimulation-based, right? TMS, trans-cranial magnetic stimulation, TACS or TDCS using electricity, vagal nerve stimulation, using light, near-infrared light. All of these are stimuli that we can apply to the brain that seem to be improving function. The question right now is, how do we apply it, where do we apply it, who do we apply it in? And then, if you're using something like TMS, for example, I have a good friend who does studies in TMS and he calls it the sledgehammer of neurostimulation because it's not very focused. So what happens is that you can open the gateway to neuroplasticity with these technologies, but you then need to direct that neuroplasticity to the thing that you want to get better at. So yes, I think these technologies are super interesting, we need to find a way to then make sure we're directing the adaptation to skill development or some other area of brain function that we want to support.

Speaker 2:
[16:39] I was just down with my partners at RMI and they have a new $400,000 piece of tech where if you have an MRI of your brain, they can put markers on your face and do real-time location of where they put TMS down to almost one millimeter precision within the brain structure. So we're doing that with stem cells on my brain. I'm about to do an episode about that. It's profound, but it's very unusual technology to be able to do it now, but it'll get easier over time.

Speaker 1:
[17:10] I'll say that again.

Speaker 2:
[17:11] Then on the TDACS front, the Russians came up with this idea for the space program to reduce the amount of sleep that you need. So I've had a TDACS device since the late 90s, and I use it pretty regularly, and I noticed massive changes in fixing my broken brain from when I was young, where a little bit more electricity seems to go a long way. I wonder why it's not more widely deployed right now. You pull a clip on each ear, run a little bit of current, and most of the time, the brain will adapt to more electricity. Is there a reason we're not doing more of that?

Speaker 1:
[17:45] I think with that kind of advice, is that meant to be like an auricular vagal nerve stimulator? Or do you know what the current it is that you're using?

Speaker 2:
[17:53] It's not at all a vagal. It's basically just alternating current between the ears.

Speaker 1:
[17:58] So you stimulate both ears at the same time?

Speaker 2:
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Speaker 1:
[20:50] I think that one of the reasons why this isn't used extensively yet is because we're still figuring out those parameters, at least within the setting of developing the evidence that we would use to deploy it widely, or if it's going to be used as a medical device. So, like, I'm part of a group at the Institute for Human and Machine Cognition. Like, we have a DARPA-funded grant to try and develop a device that would then decrease the amount of sleep that people would need, or would actually would allow people to maintain performance under significant sleep restriction, which is very relevant to many military groups. But it's going to be a combination of these stimulation technologies.

Speaker 2:
[21:28] It is. Yeah, the Russians got into that in, like, 1950. It's kind of funny. But I think there's a lot of open science territory there. I love it that you're working on that. Because it's not just military applications. I would like to not drive into a bridge if I'm really tired late at night.

Speaker 1:
[21:44] I'm driving.

Speaker 2:
[21:44] Everyone could use the ability to function when we're tired because a lot of people are tired. So I think this is missing knowledge from the database of human enhancement technologies.

Speaker 1:
[21:54] Yeah. And I think that's only going to come. And there are a lot of people working on this. So then it's just figuring out how can you build this thing at scale? How can you make sure that your sort of timing stimulation based on, you know, in internal electrical or other rhythms, right? So if you're using a stimulation device during sleep, how are you timing it to sleep spindles and other things? So you need some kind of like internal loop to measure that. So I think this stuff is coming. And yeah, I'm certainly excited to see where that goes. So cool.

Speaker 2:
[22:27] All right. Let's talk about cognitive decline. Is this just a normal thing or is this self-inflicted after about age 30?

Speaker 1:
[22:36] So it's probably certainly right, we can't yet completely prevent the aging process, right? I know some people are working on that. But, you know, so some decline may eventually happen. But a lot of what we expect happens is largely driven, I think, by almost starting with societal expectation of what happens, which then becomes a self-fulfilling prophecy. So going back all the way to like the beginning of the 20th century, there were people like Sir William Osler, who was a physician, he helped found Johns Hopkins Hospital. And then he was a professor at Oxford. And so many of the things at my medical school are named after him. And he helped to popularize the idea of retirement. Essentially by telling people that once you hit 60, you're essentially useless and you need to be put out to pasture. And we have then internalized that as a society, and we expect significant loss of function by that, you know, the end of our sort of fifth or sixth decade. But in reality, we have a huge amount of evidence that doesn't need to be the case. So there was one study that was done actually in Seattle, the Seattle Longitudinal Study run by Professor Warner Shiey, which for the first time, rather than taking one big population of people and doing, you know, measuring their cognitive function and seeing that on average, right, cognitive function declines from about age 30, like you said. But it's very different looking at a population and thinking what's the cognition of an average 70-year-old versus what's my cognitive function going to look like when I'm 70, right? Those are not the same thing. And so what Shai showed was that if you measure cognitive function in the same people over decades, the majority, and by majority I mean more than 50%, maintain cognitive function well into their 70s and 80s. So yes, the average goes down as some people lose function, they kind of drag the average down. But most people actually maintain function out much later. And those data are actually used to raise the retirement age in the US in the 80s. So a lot of what happens is that as we get past our period of formal education, which is the time when cognitive function on average starts to decline, is we just stop doing the things that build and maintain cognitive function. We stop learning new skills, we stop challenging ourselves, we stop exercising or moving as much, we stop sleeping as well. And part of that is because we expect it. Right, so there's this idea of stereotype embodiment theory. If we think that we're going to lose function with age, we stop doing the things that prevent the processes of aging and therefore it becomes a self-fulfilling prophecy. So I think that this can't be entirely prevented, but a lot of it comes from what we expect of ourselves and then how we behave as a result.

Speaker 2:
[25:37] You didn't mention alcohol. Do you drink?

Speaker 1:
[25:40] Occasionally, yes, but not regularly.

Speaker 2:
[25:44] How bad is alcohol for your brain?

Speaker 1:
[25:47] For a long time, we were told that a drink a night is going to be beneficial. We know that alcohol particularly impairs REM sleep because of the REM sleep deficiency. REM sleep is really critical for creativity, integrating new information into a bigger picture of things, emotional processing. So I think one of the reasons why regular alcohol consumption is associated with increased risk of dementia is because of its impact on sleep. Overall, it looks like if you're averaging less than half a US drink a day, and this is actually based on UK Biobank data because one drink in the UK is half the size of a standard drink in the US. It's eight grams of ethanol in the UK and 14 grams of ethanol in the US. So if you're averaging less than half a drink per day, there seems to be no net effect on brain volume or dementia risk. If you're drinking more than that, so you're drinking more than a drink every few days, that seems to then be associated with smaller brain volumes and an increased risk of dementia. So yeah, the occasional drink I think is just fine. But if you're drinking alcohol regularly, there's evidence that it's going to start to be detrimental for the brain.

Speaker 2:
[27:03] That is the occasional drink, not the occasional drinks with an S.

Speaker 1:
[27:07] Yes. Yeah. So it's like one or-

Speaker 2:
[27:11] Drinking five on Friday is bad.

Speaker 1:
[27:13] Yeah. Yeah. Yeah. So you need to average two drinks a week or something like that.

Speaker 2:
[27:19] But if you had them both on one night, it's going to have a much different effect than if you had a little sip every night, basically.

Speaker 1:
[27:26] Yeah. It is hard to pass that out. But I think at that level, it probably wouldn't make that much of a difference. But if you're having multiple drinks or you're drinking four or five drinks in a night regularly, then I think you're reaching that point where we're going to see a negative effect.

Speaker 2:
[27:44] Yeah. I would just say the safest level is none, or the rule I follow is I'll drink it if it's older than me, because I really can't afford it at that point.

Speaker 1:
[27:56] I think that's fair. I will say that some of the recent evidence that no alcohol consumption level is safe, is based on a really sketchy statistical method that I'm not sure I believe in. But equally, I think that regular alcohol consumption is definitely not going to be great for any aspect of your health.

Speaker 2:
[28:17] Also, the goal of life is not to be safe. The goal of life is to actually live. I do make danger coffee, not safe coffee. For a reason, because almost everything that's worth doing has some inherent risk. So, if two dropper fulls of alcohol isn't as safe as no alcohol, but it's still just about as safe, then who cares?

Speaker 1:
[28:39] Deal with it.

Speaker 2:
[28:40] So, practical matters, we'll put it that way.

Speaker 1:
[28:43] Yeah.

Speaker 2:
[28:44] Now, one of the things that's just all over Instagram and all is ADHD. So, how's an ADHD brain biologically different from a normal brain, if there even is one?

Speaker 1:
[28:56] This is a fundamental question in neuroscience right now is like what is a normal brain? I think that there does seem to be in a proportion of individuals who are diagnosed with ADHD, there is some kind of, I hate to use the word imbalance, but there is some kind of altered balance of inhibitory and excitatory networks, which then shape how those people are able to direct their attention. This also affects a whole bunch of other things related to mood, and energy levels, and motivation. Because hyperactivity is in the name, everybody assumes that people with ADHD are just consistently all over the place, but that's not really true. They certainly have peaks and dips of focus, and attention, and mood, and energy, just like the rest of us. There's maybe some altered balance of the neurochemistry that drives those things. In some individuals, there is evidence that those shifts are brought back to whatever the quote-unquote normal brain is through the targeted use of stimulants, modafinil as an example. Because in those who don't have a diagnosis of ADHD, if you give those kinds of stimulants, what you often see is an increase, right? You sort of push them over the edge of that arousal curve. So they've done studies where they give people these stimulants, methofenadidine, daphnil, et cetera. And then they look at complex cognitive performance on cognitive function tests. And what you see is that they feel good and they think they're performing better, they actually perform worse because you sort of over-arouse them. And again, this is in people without ADHD. Whereas in some people with ADHD, you actually see the opposite effect. They are better able to perform sustained attention and focus on these kind of complex cognitive tasks. There is some discussion around what are the environmental contributors to this. Certainly, are kids sleeping properly enough? Are they overstimulated? Are they not getting adequate physical activity, which is certainly going to be an important part of brain development and function. There is certainly going to be an environmental component here, but it seems that one of the things is this altered balance of stimulation within the brain, which can then be, and then they respond differently to stimulants in a way that improves focus and attention, whereas it might do the opposite in the rest of us.

Speaker 2:
[31:34] What does nicotine do to a young brain versus a middle-aged brain?

Speaker 1:
[31:39] The reason why it has the effects that it does is because it stimulates nicotinic acetylcholine receptors in the brain. Colon-energic signaling or signaling with acetylcholine, really important, again, for focus and sustained attention, for memory encoding. Colon-energic signaling is something we actually lose as we get older, or with the processes that may result in dementia. It's one of the reasons why a first-line therapy in Alzheimer's disease is a colon-esterase inhibitor, right? So you're preventing the breakdown of acetylcholine in the synapse, so you can help to maintain memory encoding and some aspects of executive function. So we know that the nicotine in small doses, like they've been done in the studies of 1 to 4 milligrams, something like that, can improve several aspects of acute cognitive function related to focus and attention. I think that what we know best is in the general adults, these studies are usually done in people in their 20s to 40s or something like that. And it works the same in those who are nicotine-naive or not, so looking at people who smoke or not, at least back in the days when smoking was the primary source of nicotine. In the young brain, I think we do fewer of those studies just because you don't want to give 12-year-olds nicotine in a randomized controlled trial. But we know these signaling processes are kind of related. But, equally, I know several other ways to augment nicodinergic signaling in the brain related to arousal and all these other things that we talked about already that are going to improve sustained focus and attention without manipulating it pharmacologically. Later in life, if we've lost some of that signaling, there's potentially scope in many ways to improve that. And again, could be done without pharmacological intervention. There was just a study using a cognitive training program, one particular program that's actually been studied and showed to decrease the risk of dementia. And by doing this cognitive training, they saw improvements in coanalytic signaling in areas of the brain where it tends to decline with age. So that's where nicotine can improve focus. We know that in the adult brain. But equally, I also know ways to improve that signaling without the need for pharmacological intervention.

Speaker 2:
[33:57] It feels like there's other things happening with nicotine. Not just the acetylcholine receptors, you're getting mitochondrial uncoupling that doesn't happen with any other compound to the same degree. So it could be a mitochondrial performance thing, PGC1 alpha, a bunch of other things like that. But I didn't get really clear like, like it's bad for young person, let's say teenage and one to four milligrams is a very small microdose that helps with ADHD and older age, at least in my longevity book. You might want to consider a very low dose of oral nicotine, not smoking, in order to help protect the brain. I'm just trying to figure out, is this a good thing in your 20s or is this not a good thing in your 20s, just from a scientific perspective?

Speaker 1:
[34:46] What I would say is it's hard for me to say it's not a good thing, but it's not something I would recommend necessarily because there are other environmental factors that are going to influence the performance of these systems, that we do know translate to improvements in headroom, cognitive performance and long-term risk of cognitive decline. And, right, nicotine does have the potential for tolerance, dependence, right? And we don't necessarily want to start, I wouldn't want to start that early. And I still would say even though there's evidence that nicotine enhances cognitive function, I would say there's better evidence for other factors that act in those same pathways, right? So we know that aerobic exercise similarly has some of those mitochondrial benefits, activates some of those same pathways, including in the brain without the need for nicotine. So while I understand why some people use it as a cognitive enhancement, I don't think it's necessary as part of this long-term longevity brain plan.

Speaker 2:
[35:57] I don't know. If I had a half hour to do aerobic exercise or 30 seconds to take 2 milligrams of nicotine and then do something else in my half hour, I kind of think one's more necessary than the other, but I don't know. Am I weird?

Speaker 1:
[36:12] Well, that's a very loaded question, Dave. I think that you would want me to say that, yes, you are weird. Weird? Right. But we know that everything has a trade-off. So while I would not routinely recommend nicotine use, I understand why some people do use it. You're right, there's a trade-off. We only have a certain amount of time to focus on these things. I think there are additional benefits from aerobic exercise, and you're probably going to do the kind of exercise that's going to stimulate these pathways if you're interested in longevity anyway. So, yeah, I don't think there's necessarily a massive trade-off there. But I certainly understand why some people are interested in it.

Speaker 2:
[36:57] Do you ever use it for cognitive enhancement?

Speaker 1:
[36:59] I have done, but I don't routinely do so anymore. Like most things, if I'm going to talk about them, I feel like I should probably have tried it and experienced it as well as read the research. But, no, I don't use it routinely.

Speaker 2:
[37:11] And you chose not to use nicotine routinely for what reason?

Speaker 1:
[37:14] Primarily because I like to focus on the things that I know I'm going to sustain long term, that I have better evidence for long-term impact. So, like, I don't have good evidence that regular nicotine use is going to decrease the risk of dementia, for instance. Right, I know it has an acute effect. There are some studies that suggest, like, nicotine use may decrease the risk of Parkinson's disease, for example. Some people have been interested in it from that standpoint. But in terms of where I...

Speaker 2:
[37:45] Yeah, since 1926.

Speaker 1:
[37:46] Yeah, but in terms of my framework, like, in terms of where I put my time, it's in things that I feel like I'm going to sustain long-term, that have the evidence that I'm comfortable with in terms of long-term risk. If that changes, and nicotine becomes a thing where that fits into that framework, I'm very happy to change my mind.

Speaker 2:
[38:08] How about creatine? What's your take on that?

Speaker 1:
[38:10] Yeah. Also having a moment on social media. And I feel... So creatine, I do take creatine every day. One, for its performance-related effects. So, you know, I'm a competitive, strong man. So I feel like there's good evidence for its performance enhance... You know, physical performance-enhancing effects from a strength and power perspective. From a cognitive standpoint, the... sort of the best evidence suggests that it does have an effect, particularly in older individuals or individuals who have already lost some degree of cognitive function. Probably because, right, we know it's important for the energetic status of the brain as an intermediate for, you know, moving electrons around. Or moving phosphate groups around, sorry. We also have some evidence that it may be beneficial in those at high risk of concussions. Like, particularly like subconcussive impacts over a season, say, in football players. There was one study now in early Alzheimer's disease where it seemed to show some benefit. Another study in post-menopausal women, again, seems to, you know, randomized control trials may support the treatment of depression in those who have treatment-resistant depression. So, lots of interesting things with creatine when it comes to the brain. So, it is something that I take, and it's the one supplement other than vitamins that I recommend people consider in my book.

Speaker 2:
[39:42] I'm with you there. I think the preponderance of evidence on creatine is pretty good for cognitive function and probably dementia and Alzheimer's, but we shall see. If I just did zone two cardio for years, what would I be missing out on cognitively?

Speaker 1:
[39:59] That's a great question and it probably starts with what your starting point was, right? So, if you were completely sedentary to begin with, then zone two cardio is going to be a great place to start, and one of the first studies ever done.

Speaker 2:
[40:13] If you don't want eight hours a week.

Speaker 1:
[40:16] Yeah.

Speaker 2:
[40:18] Sorry, it's hard. I didn't mean to interrupt you. We just have a flag online. So, but like, okay, so start, there's eight hours a week of mostly a now discredited longevity upscene guy going, you have to do zone two forever, but you can raise, you can raise your VO2 max in far less time than zone two. So I feel like, ah, why are we telling people to do the least effective way to raise their VO2 max? Because like, if you have parenting or a career or you want to write a book, it feels like, like this is one of those things like, work out more and eat less and you'll lose weight, but no one can actually do it and then still live their life.

Speaker 1:
[40:55] So to clarify, I would never tell anybody to do eight hours of zone two a week. I think that is a comp- I think, like, if you have eight hours to train a week, there are many better things that you can do. If you can build this, right, so if you can build this, this is a brisk, a brisk walking program, you do 40 minutes of brisk walking a week, that's kind of zone two-ish. We know in older adults that improves hippocampal size and function, right? If you have a small amount of time to exercise and walking is your best strategy that's just going to get you moving, great. But we also know, like you said, that the vast majority of benefit from exercise has an intensity component. It's intensity dependent. There were other studies, where there was a study published a couple of years ago, where they took people and they randomized them into three groups. There was a control group, there was a jogging group, so there's kind of like a zone two-ish group, and then there was a high intensity interval training group. So like it was the Norwegian 4x4 protocol, if anybody's familiar with that. So four minutes 85 to 95 percent of maximum heart rate. Yeah, it's rough, right. So like four minutes on, three minutes off, times four, they did that three times a week, which is incredible. And then they did that for six months. And what they saw was that the interval training group had much greater improvements in hippocampal structure and function than the jogging group or the zone two group. And maybe the jogging group kind of got into zone three, but it was still kind of lower level intensity. And those benefits would maintain for five years. So we know there's an intensity component. And the primary driver of that is probably lactate, because lactate as a signaling molecule easily gets into the brain and switches on the production of BDNF, brain-derived neurotrophic factor. So if you're starting from nowhere, do some kind of activities that have a zone two kind of level intensity as you get kind of comfortable exercising. Great. But beyond that point, we know that some of these pathways are intensity dependent. And that's just in the sort of like the interval training or more aerobic side. We know there are separate benefits for the brain from resistance training and again separate benefits from co-ordinative exercise, you know, ball sports, skill sports, board sports because of the way that they stimulate the brain. So there's a whole bunch of stuff. If you got eight hours a week to train, you can maybe spend a couple of hours doing low level activity like zone two ish. But I would focus on those other areas because you're going to get bigger benefits there.

Speaker 2:
[43:29] Makes a lot of sense. It just seemed like one of those least effective things. You should get strong into your high intensity intervals. And then if you still feel masochism and have lots of time to waste, you could do some zone two.

Speaker 1:
[43:40] Yeah.

Speaker 2:
[43:40] But it's probably meditation might be more ROI. Just saying. And I understand I'm somewhat of an outlier, but not that big of an outlier when I talk with longevity doctors. They're like, going for a walk is a good thing, but you don't have to do that zone two thing. So it feels like it might be a little bit overblown. Now, is lifting heavy enough or is there something else we need to be doing for our brains when we're in the gym?

Speaker 1:
[44:06] So, like, basic heavy lifting is a great start. And there are studies, again, in older adults, you have them do the most basic resistance training program, two times a week, three sets of eight to twelve reps of five to six exercises that cover every muscle group. That improves the structure and function of the white matter of the brain, which is really important for executive function, rapid decision making, processing speed. And then you see improvements in those cognitive functions as well. So that's a great start. Anybody can do that, right? But you could also do it with bands, you can do it with whatever stuff you've got lying around the house. As long as it doesn't have to be eight to twelve reps, we know that the benefit of resistance training, if it's lighter, you just do more reps. As long as you're getting close to muscular failure, you're going to get some of those benefits. A lot of this seems to be related to IGF-1 production. IGF-1 we know is really critical for the development of white matter, the maintenance of white matter structure. Anything that loads the muscles, applies some mechanical tension, is going to drive the release of IGF-1. You could do blood flow restriction training. I think that's going to have a lot of similar benefits if you don't have access to heavy weights or you don't enjoy lifting heavy weights. But then there's other benefits to actually loading the skeleton, because we know that releases things like osteocalcin that could also have benefits to the brain. So yeah, a number of different ways to do it, but many different aspects are then going to benefit brain function.

Speaker 2:
[45:37] I love it that you talked about blood flow restriction. That was a big part of Smarter Not Harder, my exercise book. Just saying we have to get the signal in there one way or another. I just want to get a strong enough signal with the right recovery thing. That's behind Upgrade Labs, the AI Longevity Centers. I'm opening all over the place, just because it doesn't have to hurt and take a long time and be exceptionally difficult to fix the skeleton of the muscles or the metabolism. All of those are kind of before what happens in the brain, which ultimately, who wants a body that works well when you put your car keys in the refrigerator and don't know your name? You got to do both.

Speaker 1:
[46:14] Yeah. Luckily, when you do those things to the body because of exokines and myokines, you're getting those signaling molecules into the brain better than driving improvements in structure and function. As long as you're applying that stimulus, and in particular because most people, as they get older, it might be common to, you just get on the stepper or the cross trainer or something and you do that for an hour and then you go home. You're only doing that zone two level of intensity. But as soon as you start to add intensity from sprinting or from resistance training, there's a whole bunch of additional benefits you're going to get and then the final part being, can you make some of that, some kind of co-ordinative movement? Because we know if you compare two types of exercise that have the same physical intensity level, like cycling versus dancing or versus badminton, you're going to get additional cognitive benefits from that more complex sport. So that's a nice way to add additional cognitive stimulation from any kind of exercise that you're going to be doing. Like have it be some, require some complex skill, processing, multi-sensory kind of interaction at the same time.

Speaker 2:
[47:31] I love it. Even yoga, Turkish get-ups, anything that's going to cause you to use your vestibular system in addition to putting on strength, seems like it provides additional benefits because when you get old, if you fall over and break a hip because your balance sucked, all that zone too wasn't going to save you.

Speaker 1:
[47:47] Yeah, absolutely.

Speaker 2:
[47:48] All right. I want to talk about something that's applicable to all ages, maybe even more when you're younger, but is boredom necessary for cognitive resilience?

Speaker 1:
[47:59] One thing that we know about the brain, and I again would relate it to the idea of physical stimulus, is that periods of downtime are required for adaptation and connections and things to be made. And so what that looks like, or what it looked like in a scenario where we had to be bored, is periods of boredom, like low level, like no cognitive stimulation where new connections are made, like creativity tends to increase. But it's also a period of time when you're actually adapting to an integrating stimuli that you've already received, right? It's just like periods of sleep and recovery after physical training. We can go through a whole day without any period of that kind of cognitive downtime, which then means we're reducing the amount of time that we spend sort of adapting to, but also integrating cognitive stimuli and ideas and knowledge that we've received. So some kind of scenario where those processes are decreased, right? The process of focus and attention are really decreased and we just allow the brain to idle and then be bored and or make new connections are critical. And that's probably a big thing that we're missing a lot right now. So one reason why I think that the title of my book is quite provocative is because I think at the same time we are both under stimulated and over stimulated, right? We're not doing complex skill learning and these kinds of things that we know build function, but we'll also have this chronic low level of stimulation. That means we never get bored. That means we never actually allow ourselves to switch off.

Speaker 2:
[49:49] So then how bad is ChatGPT for your brain?

Speaker 1:
[49:54] It entirely depends on how you engage with it. I think the way that most people engage with it, it's probably really bad for your brain. And we're still waiting for some more evidence to come in. But I'll tell you exactly why I think that's the case. When they've done studies looking at brain network activation in individuals who are doing some kind of cognitive task with or without the help of ChatGPT, so there was this big famous study done at MIT. I'm not sure if it's even been formally published yet, but it came up online as a preprint. The social media went crazy. I'm pretty sure most people didn't actually read the full study because it's like 220 pages long or something. It's a very intense study.

Speaker 2:
[50:40] I had ChatGBT read it for me, though, is that okay?

Speaker 1:
[50:44] There's an Easter egg in there because there's text that isn't black. So when you read it, you won't see it. But ChatGBT does see it, and they put that in there on purpose because they knew that people were going to do that. So what you see is that when people are in... So this was in an essay writing task. And so if people just use ChatGBT to write an essay, they had less activation of the brain networks associated with writing the essay. The essay they produced was a lower quality and more similar to others. And they remembered it less well because they weren't engaging their brain in the process. And all of this makes perfect sense. Their brain didn't do the work. So they didn't get any of the benefit of doing that work, including feeling ownership of it and then remembering it. But there was a group where they did the task. First, they had to write the essay using their brains. So whatever they knew, whatever knowledge they had, they had to write that essay. And then afterwards, they got to redo it with the help of ChatGPT. So at this point, you're like, this is what I wrote, what am I missing? What could I think about? What could I add? What should I do differently? What should I improve? So you can use these tools as a cognitive orthotic to build on your current capacity and learn things better, learn new things, but it requires you to engage your brain in that process. If you just make the tool do the work for you, you will lose that skill and the associated networks in the brain, or you'll never develop them in the first place. So it is all going to come down to how we choose to use those tools. Are we using them to do the work first and then extend our capabilities, or are we just letting them do all the work for us, and then I think our brains are going to suffer as a result of that.

Speaker 2:
[52:32] Give me a little bit more of an example of how someone could use, be really specific, and if I wanted to use Chad GPT or maybe one of the better AIs, like kind of paint a picture. So how would I use it in a way that's going to make my brain better versus a way that's going to make my brain worse?

Speaker 1:
[52:47] The first step, regardless of what this is, so you're writing an essay, doing research for a presentation or a piece of writing, a blog post. Anything that you're trying to, any piece of complex work that you're trying to do, the first step is to in some way do it yourself. You assume that you didn't have access to this tool, actually physically do the work. Because we know that the process of engaging in this, first of all, doing this kind of deep work, whatever it is in terms of research, problem-solving, writing, for instance, we know that engaging in that helps to maintain our processes of focus and attention, and it's critical for maintaining the structure and function of these networks that are then going to be susceptible to the process of aging. There's this thing where just the process of being focused and paying attention and doing some deep work is going to help maintain the structure and function of those networks in the brain, which is ultimately what we're trying to maintain, or whatever skill it is we're trying to learn. So then, after you've done the work, then use the tool, whatever it is, in more of a conversational manner. So it's like asking a friend to read your work for you and tell you, like, what have I missed? Like, did I do enough here? Like, where are the issues in what I've done already? How could this be improved? And so that could be the bullet points or the points you're trying to make in a presentation, or it could be in terms of fleshing out a thought process, or the evidence behind the thing that you're trying to state in whatever it is that you're writing. And so by doing that, not only are you having to engage in the process of doing the work, and using your own knowledge, we know that the expression of and using the skills and knowledge you have is another aspect of maintaining long-term cognitive function. So you have to do that first, but then by doing it in a question-driven manner, what am I missing? How could I do this better? You're continuing to engage your brain in the process of learning. And so then the thing that's teaching you just happens to be an LLM. But that's not that different from going back to research and reading a bit more and refining your ideas, or discussing it with a colleague, or sending it to an expert that you know is going to give you a good opinion. You can use it in that way, but it requires this dynamic back and forth rather than you just saying, hey, this is the thing that I wrote, could you make it better, please? That's not going to be the same thing. It still requires you to engage it in that back and forth manner.

Speaker 2:
[55:40] Okay, so the original query, write this for me would be stupid, but you could possibly say, here's a rough outline of what I'm thinking, help write that for me and then make it better.

Speaker 1:
[55:53] No, I still don't think that's enough. It could be, this is what I'm thinking, what am I missing or what should I do differently? But it still requires you, rather than just handing over the piece in bulk, you want it to give you ideas back that you then integrate yourself. If that makes sense? So it's not just like, here's what I wrote, flesh it out and make it better. It's this is what I'm thinking, what else should I be thinking about? But then the actual process of doing the work and building it in and refining what you've done is still you doing that work. It's just helping you give you ideas and filling gaps and stuff like that, that you then apply yourself.

Speaker 2:
[56:33] I use it almost exclusively for research. I'm looking for a connection between these two. I'm pretty sure it's there, help me to elucidate it, so then I can fit it in my frameworks. But it feels gross when I'm reading something online and says, it's not this, it's that. You couldn't even be bothered to write something and that whole turning a complex situation into a binary and then doing a cheap mental judo move, which is what JGPD does when it writes that way. It's like, guys, if I can see that in your writing, it's disrespectful. I'm not saying my team has never done that without my knowledge and permission with some of my content, but I yell at them every time and tell them to use AI better or have me proofread it like I'm supposed to. So it's a constant challenge for all of us. But if you're listening to this, it's not real, it's AI. You can tell if it's not this, it's that, you know it's AI. So there you go. Any other final pieces of advice that you would offer to someone like the most important thing we haven't talked about, that's going to give us better brains?

Speaker 1:
[57:36] The core concept of the book is future-proofing your brain, right? So thinking about long trajectories of brain function. Most of the things that we can do, a lot of which we've talked about, are going to improve brain function today. That's good because humans like immediate returns. We're not going to invest in something that may or may not decrease the risk of dementia in 20 years' time. So that's where a lot of those things focus. But conceptually, we also have to prepare for this idea that some aspects of the future is unknowable. So what we're trying to do is build frameworks for how we can continue to engage in this stuff as the world shifts. So something that I think we see, particularly as it relates to how we interact with technology. So zooming out a little bit from the AI example, is that people had this whole idea of digital dementia, which is an AI is like the digital dementia, could be like digital dementia on steroids almost, because you're not engaging your brain at all. But the real risk that people are worried about when we engage in new technologies, and that could be social media or smartphones or TV or whatever, is that we spend all our time doing that rather than doing the other things that we know are beneficial. So I think I'm most concerned about the potential for technologies to affect our brain, if it then means that it's detracting from our time spent, moving, connecting socially, sleeping, that kind of stuff. Beyond that, I think we should expect the way we use our brains to change over time. And that's not necessarily a bad thing, as long as the core components of cognitive function, we can process information quickly and we can make decisions quickly, we can focus and do deep work, right? What that looks like might change. So, the classic example is Betsy Sparrow's work on the Google effect. In the modern environment, people don't remember information. They remember where that information is, right? Because we have gotten to a point where we just physically can't remember everything. But I don't think that's necessarily a bad thing. It's just us adapting to use our memory in a slightly different way. And I think that's okay. So, just remembering that that's likely to happen, and we shouldn't all just be Luddites and expect us all to use our brains like we did 200 years ago. I think it's those core components that are really important.

Speaker 2:
[59:59] You know, this isn't new. We have this weird thing called the encyclopedia that's been around for a couple hundred years or thereabouts. I couldn't remember all of it, so I looked it up. Or a library. It's just we have more effective libraries now, so our ability to access and use information is greater than it was. I'm actually all for that, but it'd be helpful if you just didn't have the library do the thinking for you versus be the repository of potential knowledge to use, so I'm with you there.

Speaker 1:
[60:28] Yeah, exactly.

Speaker 2:
[60:29] I'm very optimistic that we're entering a realm where our capabilities are much higher because of this than they were, but it's gonna require some adjustments to our brains. I think the knowledge in your book is gonna help people. Are you optimistic as well?

Speaker 1:
[60:42] Yes, I am, honestly, and one of the reasons for that is because we've now gotten to the point where we know so much about what can help to either enhance or maintain cognitive function long term. We know, or we think we know, that the vast majority of dementias may be preventable based on lifestyle and environmental factors, and that just requires us to continue to engage in those things as we get older. Related to that, we also know that the majority of things like genetic risk for Alzheimer's, like the APOE4 genotype, or family history, or even polygenic risk for Alzheimer's, is modifiable based on those same factors. Even if you come in with higher risk, by attending to these things that we now increasingly appreciate decrease the risk of dementia, as well as improving cognitive function today, you can have a significant impact on your long-term risk. So I am also very hopeful because of the amount of information we now have, and it's just a case of getting it to the point where people feel able to engage in this stuff and continue to enact it for decades.

Speaker 2:
[61:50] Beautiful. Well, Dr. Tommy Wood, your new book, The Stimulated Mind. It's worth reading. It's a stimulating book, if you could say that. Thank you for studying this so deeply, and for writing about it for all of us. Guys, if you like the show, this is just right at the bullseye of the things that I've been teaching and paying attention to and sharing knowledge on. So this is just ground zero for the knowledge, for having the brain that you want, and the brain you want right now, even if you're 19 years old, or if you're 90 years old. It doesn't matter. These are fundamental things you need to know about your brain, whether we eat. Tommy, thank you.

Speaker 1:
[62:34] Thanks so much. Really, really fantastic. I appreciate you and everybody for listening.

Speaker 2:
[62:38] See you next time on The Human Upgrade Podcast.

Speaker 3:
[62:47] The Human Upgrade, formerly Bulletproof Radio, was created and is hosted by Dave Asprey. The information contained in this podcast is provided for informational purposes only and is not intended for the purposes of diagnosing, treating, curing or preventing any disease. Before using any products referenced on the podcast, consult with your healthcare provider, carefully read all labels and heed all directions and cautions that accompany the products. Information found or received through the podcast should not be used in place of a consultation or advice from a healthcare provider. If you suspect you have a medical problem or should you have any healthcare questions, please promptly call or see your healthcare provider. This podcast, including Dave Asprey and the producers, disclaim responsibility for any possible adverse effects from the use of information contained herein. Opinions of guests are their own and this podcast does not endorse or accept responsibility for statements made by guests. This podcast does not make any representations or warranties about guest qualifications or credibility. This podcast may contain paid endorsements and advertisements for products or services. Individuals on this podcast may have a direct or indirect financial interest in products or services referred to herein. This podcast is owned by Bulletproof Media.