 So I do have to just report some conflicts of interest. I do largely rely on federal funding for the majority of my work, but I also do some professional consulting, but none of that is actually really that relevant or doesn't influence what I'm gonna talk to you about today. Some philosophical conflicts, I do believe, and the reason why I'm here is that long-term brain health can be both simple and inexpensive to achieve. And I don't believe that our brains exist in silos, unlike most of modern neuroscience. So as an example, things that I am currently involved in, my day job is I direct the Neonatal Neuroscience Laboratory at the University of Washington. We try and develop ways to treat the injured newborn brain. But at the same time, I'm also involved with the BrainStorm Institute, which is trying to increase brain resilience in athletes and some military groups who are basically destined to get traumatic brain injury. How do we reduce the impact of those? And then I'm also on the Scientific Advisory Board of Food for the Brain, which is a charity that's provided free cognitive testing for nearly half a million people now and we're trying to develop lifestyle-based ways to mitigate or prevent cognitive decline. And if you were trying to apply for money for these, each one would be considered completely separate and there's no link between the Neonatal Brain and the declining brain or the injured brain in midlife, when in reality, you just have one brain and all of these things are important over time. So my unifying question, which I sort of see from day to day, so on the left, you have here, this is a baby born prematurely. This is a baby born at term that has some kind of acute injury at birth. How do I treat these brains? What do these brains need? Then on the weekend, maybe I'm working with an athlete who's trying to maintain health performance of both their body and brain. And then maybe we might be thinking about somebody who has Alzheimer's disease or chronic traumatic encephalopathy. That's the downstream effect of being hit in the head multiple times. Are there things that all of these brains need that we can sort of unify, unifying hypothesis, maybe if Mickey was here. So I came up with my three-legged stool of what a brain needs, material security and connection over a lifetime. And the three-legged stool is a bit of a cliche, so this is my three-legged brain of things that your brain needs across a lifetime, I think. So as a case study, the examples that I'm gonna use primarily come from premature infants. So those of you who don't know much about being born prematurely, this is recent data looking at gestational age, so how long you managed to stay in utero before you were born, and then rates of both survival. So this is what we call the limit of viability currently around 22 weeks. That's just over half normal gestation. And then as gestational age increases, survival increases, that's the blue here, but then say survival without any neurodevelopmental impairment also increases. So down here, it was very unlikely that if you do survive that you won't have some kind of developmental disability. And what's interesting about the premature brain that is relevant even to cognitive decline is that when you're born prematurely, you have multiple insults, inflammatory, they're often inflammation is associated with premature birth in the first place, oxidative stress, they're born into environment that has a higher oxygen tension that they're used to, nutritional issues, you no longer have the placenta providing your nutrition, so you often get things like intralipid while you're in the NICU. And then social things, so you are disconnected from the mother, there are some ways to improve that with kangaroo care, but lots of different things that then translate through to increased risk throughout the entire life. So this, something actually goes back to Kevin's talk earlier. If you look at babies born prematurely or adults who were born prematurely, if you look at how premature they were, they have an increase in how old their brain looks on an MRI scan. So they have accelerated brain aging that's directly proportional to how premature they were. At the same time, you see the same thing with how sick they were. So the sicker they were in the NICU, the older their brain looks then once they reached early adulthood. Then we see the same trajectory that continues throughout the entire lifespan. So this is data now on older people who have Alzheimer's disease, progressive mild cognitive impairment, stable mild cognitive impairment or no impairment. And if you look at the rate of brain aging over time, so this is using MRI scans and a machine learning algorithm to sort of guess the age of the brain, then if you have Alzheimer's disease or progressive cognitive impairment, your brain is aging faster. And this basically can start right at the beginning of your lifetime. And this then translates to things that we really care about like all cause mortality. And this is data now, people getting into their fifties. So the first prematurely born babies could only really be kept alive when they invented or improved ventilation in the seventies. So we're only now starting to see adults who were born very preterm survive this long, but you can essentially see the same thing about for men and women. The younger, the more premature you were, so going up here basically the earlier you die or the more likely you are to die across your entire lifespan. And so this is essentially, this slide basically should give you the entire takeaway of my talk, which is the brain, your brain and your body is the product of the environment. And actually if I look at this graph really hard, it should initiate a very severe existential crisis because what it shows is that somebody who's developing neuro-protective agents for use in babies in the NICU in the hospital, it probably matters almost not at all compared to the environment that that baby goes home to. So what this graph shows here is the level of maternal education of a baby born prematurely, so primary secondary school, undergraduate, post-graduate degree. And if you look at the amount of injury that that baby's brain has in the hospital, then and you predict what their cognitive function is gonna be like at four years of age. You'll see that those, the prediction or those who have a lower level of maternal education end up with a much lower prediction due to the injury. But if your mother has a post-graduate education, basically the brain injury that you have in hospital means nothing for your final outcome. And the important thing is that basically maternal education is a proxy for a huge number of things. So various aspects of socioeconomic status, social determinants of health, so we know that exposure to systemic racism and experience of racism actually increase the risk of prematurely in the first place, as well as affecting both neonatal and maternal health outcomes. Other things like nutrition quality, education quality, all these other things could be boiled down basically into this one thing. So depending on those things that your brain goes into, that's essentially gonna determine your brain for life. So I'll go through each of these legs one by one, hopefully within time. And my hypothesis that essentially informs a lot of this talk is that growing a brain and maintaining or repairing a brain will require similar substrates and processes unlike what most grant funding buddies would have you believe. So this, I'm gonna briefly talk about ketones just because I think they're interesting in this context. On the left hand side, you have a picture of an experimental setup of an experiment that nobody would ever be able to do nowadays but they took aborted fetuses and they took the brains and they infused them with glucose and ketones to see how much would be actively taken up. And what you see here, beta-dixibutorate and glucose on a molar equivalent, probably at least 50% if not twice as much ketones are being taken up by the developing brain in utero than glucose. And then this is a nice quote from a paper that actually built on work that was really started by Hans Krebs when he was at Oxford that says beta-dixibutorate was the preferred substrate for sterile and fatty acid biosynthesis in the three organs of ectodermal origin, the brain, spinal cord, and skin. So everybody talks about ketones being important for metabolism but when you're trying to both maintain, grow, and repair a brain, actually they're the brain's preferred source of biosynthetic materials to make new brain cells. So then we'll talk about fats, there's the other things that you need to grow a brain. And these are data taken from autopsy studies where the infants died of something not related to the brain and they looked at the amount of fats that were in the brain related to their gestational age. And I really like this study because they have gestational age in weeks. And so this is time in utero and it goes up to like 150 weeks. That's three years of pregnancy which probably most people wouldn't like to enjoy. But it's basically, so it goes up to here, this is in utero and then that's the next two years ex-utero but basically what you see is that DHA, uptake increases the main sort of long chain omega-3, a racodonic acid at a similar rate, a long chain omega-6. Adrenic acid is another omega-6 that's actively accumulated in the developing brain. You get it primarily from poultry, pork and eggs and then at almost double the rate you also get an increase in oleic acid, the main monounsaturated fats from animal foods. So it's basically in order to build a brain you need a lot of polyunsaturated fatty acids and monounsaturates. What's interesting then, and this kind of goes back to what Tucker was just talking about was that if you increase the amount of little air acid that's around you actively compete for uptake of DHA into the brain, DHA being one of the critical factors of neuronal function. So this is a study done in piglets. Piglets actually are a really nice model for both gut and brain development relative to humans and they had piglets fed regular cell milk or a formula where they doubled the amount of little air acid and actually slightly increased the alpha little air acid that's the omega-3 precursor. But what you see down here, the black bars is after the formula and you see basically a progressive decrease in the amount of DHA in the brain after doubling the amount of little air acid that was present. So then if you look at something like breast milk and Kevin won't be able to talk about breastfeeding but I'll just talk about breast milk. And if you look at breast milk in the last several decades, the little air acid content has increased at least three fold and then this is again alpha little air acid has stayed about the same. And the fat content of breast milk comes about two thirds from body fat, that's previously stored in about a third from dietary fat. So this is purely based on the amount of little air acid that's increasing in the diet and my main concern is that this is then actively competing for DHA uptake in the brain sort of on a population level. Here's an example of this. So that's one, this is one baby from that previous study I showed where instead of getting breast milk, I got a formula that had a very high ratio of little air acid to omega-3s and this is the ratio of omega-3 to omega-6 in the brain. So it's completely different, very, very low relative to normal uptake. So you can actually measure this in the brain when they've had the opportunity to do so. Low DHA itself is associated with increased risk of preterm birth and pretty much the only thing that's been shown where active omega-3 supplementation and randomized controlled trials is almost definitely positive is in preventing preterm birth in those who are at risk. We also know that if you have lower DHA at birth, you have a higher risk of bleeding into your brain which is associated with both death and the neurodevelopmental impairment. What's interesting then is when you look at trials of DHA or arachidonic supplementation in both term and preterm babies, you don't really see much benefit. It depends a little bit on the dose and timing and all that kind of stuff. But the reason why I've included this meta-analysis particularly is because they included average linoleic acid used in the formula, 17.4%. And I think at that point, basically any DHA you're getting is never gonna make its way into the brain. So then if we try and translate that into cognitive decline, there's extensive evidence that DHA and EPA, long-chain omega-3s and their intake is associated with decreased dementia risk. But again, there's minimal benefit in randomized controlled trials. And actually if you look at the DHA in the brain of patients with dementia, it's not reliably lower. Sometimes it's higher, sometimes it's lower. But we do know, and this is the study that Tucker just referenced, that if you look for oxalams, oxidized linoleic acid metabolites in Alzheimer's patients, they're elevated, you can decrease this by decreasing dietary linoleic acid intake. And we also know from some rodent studies that if you give oxalams in the diet, they can also decrease omega-3 levels in the brain even though they're not full fats. The next important thing, just to kind of tie this story together, there's an unloan modulating fat of the adipose tissue, which is a really important buffer for DHA. And we know that DHA is actively released by the maternal adipose stores to be given to the baby. And it's also stored in the neonatal adipose tissue to supply the brain as the brain is growing. This is a figure from a paper that we just submitted. And basically, the whole reason I include it is because right now there's this big drive to take fancy DHA supplements as phospholipid form. But actually, if you look at the studies where they then gave the form for more than three days, all of it evens out. So yes, if you give it acutely one dose, you're more likely to get a phospholipid form like a krill oil into the brain. But actually, the adipose tissue takes up triglyceride forms and then it just doses it out to the brain as it needs. So you don't need to take a fancy form, although ideally you would just eat fish. The final part of this story then is that you need other things for omega-3s to be useful. And this is data from the Vitacog study done at Oxford where they gave various B vitamins. So this was actually B6, folate and B12 to reduce brain atrophy in people with mild cognitive impairment. And they saw that you only saw benefit. You only saw a decrease in the rate of brain atrophy in those you had higher levels of omega-3s. So all of these things interact. So to kind of summarize that, I think ketones are interesting probably for reasons other than why we usually talk about them the very important metabolic precursors. DHA is critical for brain growth and repair. In my mind, it's perhaps the strongest case providing high linoleic acid intakes, particularly in development. And long-term intake is probably more important than supplementation. And then to go back to Diana's talk yesterday, the two long didn't read like growing brains, kids, they need animal foods, really, really critical. You can do whatever you want when you're not an adult but don't do it to your kids. So the middle thing that I'm gonna talk about is security. And there's many, many things that go into this in terms of toxic exposures and all that kind of stuff. But I'm gonna talk mainly about glucose and muscle mass. So again, if we go back to babies born prematurely, if you look at their risk of insulin resistance and associated syndromes, you see that babies born early preterm and then late preterm are sort of dose-dependently have an increased risk of high blood pressure, obesity, metabolic syndrome and fatty liver syndrome. And this is just like the first, like I've said, this is kind of the first chance we get to see it, but it seems like the more preterm you are, the more likely you are to be insulin resistant. Then translating to cognitive decline, we know that if you're pre-diabetic, you don't have to be frankly diabetic. If you're pre-diabetic, you have about a 70% at least increased risk of having some kind of dementia. Similarly, if we then look at the age of your brain, this is similar data to what I showed you earlier in patients with diabetes. If you look at those in the top 25% of fasting blood sugar versus the bottom 25%, you have a big difference in terms of how old their brain looks. So higher blood sugar, particularly persistently, seems to be directly involved in the aging of the brain. And one of perhaps even a better predictor than of this than fasting blood sugar is dynamic changes in blood sugar. So this is nice data from a Japanese trial where they gave dipeptidal peptidase for inhibitors, which actually decreased the metabolism of increases. So I'm ticking off all the different talks that I'm referring to. But basically, and that includes blood sugar control. At the beginning of the two year study, they looked at mean amplitude of glycemic excursions. So how big are the glycemic excursions? And the bigger the excursions in an individual, the worse their cognitive function. And the bigger the improvement in their glycemic excursions, the bigger the reduction, the better their improvement in cognitive function. So you can actively reverse this process over time. That's the important thing, right? This isn't a fixed problem. One thing that's very interesting if we're talking about glycemic excursions is that what we know now is that basically, from a food, you cannot tell how an individual responds. So this is data from one study where they looked, trying to predict the glucose area under the curve after a meal. And better than just looking at the carbohydrates in the meal, was looking at an individual's blood sugar control with HBO and C. So just looking at carbs in a meal, just looking at the quote-unquote glycemic index will probably tell you nothing and you need to take some more accurate measures. This is important if you wanna live a long time as well because this is data from the Baltimore Aging and Longevity study. And what they've done is an oral glucose tolerance test in people by decade. And what you'll see that as the decades go up, the glucose peak goes up and up and up until a spike at 60 to 69. And then it's slightly better in the 70 year olds and then slightly better again, 80 year olds. And my main takeaway from this is that if you want to make it to be 70 or 80 so you can even be included in the study because you're still alive, you need to have better blood sugar control. Which then brings me on to muscle tissue. And your muscle tissue is basically your best buffer for circulating blood glucose. This is a nice study where they could look at, where they took people and they trained just one of their legs for 10 weeks and then they looked at the effects of acute training, detraining and what you see, so they did an insulin clamp to look at glucose uptake which is not really physiological but you see even a baseline in the trained leg versus the untrained leg, you have two to three times the glucose uptake per kilo of muscle tissue. So the more muscle you have and the more active it is, the more glucose uptake you get. And this kind of ties up multiple different things that basically say muscle does everything that you need to do in order to reverse or prevent the process of aging. So not only is muscle and the movement of muscle actively anti-inflammatory and has benefits of glucose up taken, hormetic stress improving resistance to reactive oxygen species but being sedentary is also the direct opposite. It is directly pro-inflammatory. So you see similar things again if you're trying to grow a brain, particularly one that's at risk. So if we look at babies born prematurely, increased fat-free mass secretions, that's basically increased muscle mass gain and so is associated with improved processing speed and improved processing performance, decreased risk of any type of neurodevelopmental impairment and higher IQ and particularly this one study, so that's a summary of several studies but this one study, just looking at pre-terms, particularly over four years, the more muscle mass they gained that was associated with an increased IQ and processing speed. And we see the same again in patients with cognitive decline. So here, this is a study where they looked at, where they looked at different parts of the body composition and total volume of the amount of brain matter that somebody has after adjusting for the size of their skull which is obviously different from person to person and you see things like a BMI wasn't really predicted, predictive fat mass wasn't predictive but lean mass was significantly associated with the amount of brain that you have. So the more muscle you have, the more brain you have. Here, this is data from the UK Biobank study where they looked at lean mass, muscle tissue and a marker of fluid intelligence and you see, as you seem to be more predictive in females than in males but essentially and lots of variability as you'd expect but a positive linear correlation between the amount of muscle mass you have and fluid intelligence. We know that exercise is neurotrophic which probably plays a big part of this. The first time that we saw in a clinical study that you could actually increase the size of the hippocampus in somebody who was older in their 60s included a study where they did walking for 40 minutes, three times a week and that significantly increased the size of the hippocampus on MRI and the grade to the improvement in cardiovascular fitness, the bigger your hippocampus got and the same thing and that seemed to be tied to BDNF production. So then you probably want to know how much is enough muscle and there was a study that used the NHANES data that said that you need to be on about the top 50% of the population to have sort of the highest or the best longevity compared to the lower 50%. But that's not particularly useful because you might know from epidemiology studies they say this is the top 50% but they don't tell you what amount of muscle those people actually had. So these are analyses that I did with that same data and this uses the fat-free mass index FFMI which is basically your BMI after you've taken away body fat. And so for women, the confidence intervals cross zero so here risk increases, mortality risk increases as FFMI goes below 14 and for men it's 17 but ideally you probably want to be closer to 17 and 21 it seems like and that's not that much so that's the important takeaway is again it's somewhere near the top 50% of the population this is definitely achievable by anybody. If we then look at the additional benefit of that on mortality so this using biological age derived from various blood test markers and adjusting for sex and body fat percentage I looked at how much does each kilo of muscle reduce your risk of mortality? It's about seven percent and then for each one you add to your FFMI above those limits I showed earlier 14 or 17 so this is for the average person it's maybe eight to 10 pounds of muscle you get a 22% reduction in mortality risk. So to summarize that part, more bigger, more brainier your muscle mass is a critical organ both as a glucose sync anti-inflammatory neurotrophic but it requires physical movement and if you aim to be in the top third to 50% of muscle mass or strength as associated with significantly improved longevity and probably and brain volume and brain health as well. So the final thing that I'm gonna talk about is connection and particularly connection to the physical world around you. So somebody previously in the conference mentioned the phrase use it or lose it and it's interesting because if you look at the age where people retire it seems that even after you adjust for things like medical conditions and other things that would make you retire earlier the earlier you retire the earlier you die and there may be several biological reasons for that. So if we think about trying to build and develop a brain in the first place we should think about what does it take in terms of nervous system demands to do that? So this is a graph I've made arbitrary units of nervous system demands to kind of showcase this and a lot of this stuff and the slides coming up are from a close friend and colleague of mine, Dr. Josh Turknit who's a board certified neurologist and you'll see his name pop up a few times but basically if you're trying to learn to walk, learn to talk, you're trying to learn social interaction these are incredibly difficult tasks that require a huge amount of neurological and motor effort and so you start with this in your first few years of life and then you learn to drive and that's still difficult but it's probably less difficult than learning how to walk in the first place and then you go to school and you learn biochemistry and you learn the Krebs cycle even though it's difficult it's not as hard as learning how to like socially interact with other people. And then you go to work and then you retire and then you think well I should do some Sudoku because I'm not using my brain. And I probably add arbitrary random online brain training here as well because it just doesn't require the same demands as some of these other things. So the summary of that is that there's a massive discrepancy between what you do early in life to develop and wire your brain versus what you do later in life in terms of the demands that you then put on your brain. And there are some other ways that we know we can grow our brain matter. So this is a super interesting study where they looked at taxi drivers in central London to be a traditionally to be a taxi driver in central London, you had to learn the knowledge which is basically this entire map of six miles around six miles circumference around radius around chairing cross station. So you basically should be able to get anywhere in this area in London without looking at a map. And when they looked at the brains of people who who passed the exam they actually had an increase in gray matter on the MRI and those who failed didn't get that increase and then controls also just stay the same. So actively challenging your brain. I mean, this is really difficult as you're surprised to learn that, you know, it has this benefit on the brain. I don't support what you just said. And so similarly, it's important that what you're doing is actually a significant challenge. So this is again, this is a study where they looked at all the different times they looked at this brain age metric. This is MRI metric looking at how old your brain is. Professional musicians, so these are people on average in their twenties. Professional musicians have a lower brain age but amateur musicians have a significantly greater benefit. And it's because they're bad at it. So you're playing your musical instrument, but it's hard. And once you get good at it you don't get the same benefit. And so because Aaron's here I thought I'd talk about bird brains. Wait, I mean, because Aaron's here I'm gonna talk about the brains of birds. And these are a series of experiments that were done by Eric Knudsen in Stanford. And what they did is they put on barn owls, they put these prisms that shift vision. And what it does is it causes a mismatch in the superior calculus, which is what maps sensory inputs into like physical space. And what they saw is that juvenile owls rapidly rewire. So you put the prism on and they can really quickly figure out where they are in space. Adults, adult owls don't do that. However, if you make the increments smaller or you force them to do something like it they really need to be able to rewire. So they did this with hunting then you actually see a greater improvement. And so this is something just showing that. So here, this is the interoral timing difference. That's basically a measure of the map shift in the brain. And so if you don't make the adults hunt they don't get much of a shift. But if you do make them hunt, they do. And then that improves their accuracy in actual hunting. And so the reason why this is a necessity if you wanna eat, you have to be able to figure this out. And so these studies have been slightly misconstrued recently as being like directly relevant to humans. But what's interesting is that prism studies have been done in humans since basically of the late 1890s that were first done in Berkeley. And then a lot of it was done later in Innsbruck with the Innsbruck Goggle experiments. And so there's some evidence that older adults adapt more slowly similar to the owls. But I don't think it's relevant over important time scales and it's probably driven by necessity and interaction with the environment. So actually physically going out there and experiencing the environment. So this is one study where they use prisms to shift the visual field and then you have to throw balls to hit a target. And older adults, these are people in their 60s, they took more throws to end up hitting the target. And then when you took the prism off, it took them longer for them to figure out back to normal. However, I don't think this is necessarily that relevant to real life. This difference you're still adapting within a short period of time. This is a quote from some of the Innsbruck Goggle experiments where they completely flipped somebody's vision and then forced them to use that all the time. And so they say, between the first and third day, the world was upside down to the participant. There were many mistakes in grabbing objects and moving. By the fifth day, things that had been seen upside down suddenly were upright once the participant brought their hands into the picture. From the sixth day of uninterruptedly wearing and reversing spectacles, permanent upright vision and shoot and behavior was perfectly correct. So basically, within six days, the adult brain can completely rewire where it is in physical space. Isn't that cool? And so I think this is important because challenges to the vestibular system to your position in space probably have a greater existential threat or associated with a greater existential threat. So they are a greater drive for plasticity. And so you see here, this is a study where they took older adults and they either put them in dance or sport. This is like a circuit training. And in the dance group, they saw a greater increase in the size of the hippocampus on MRI. This is a recent meta-analysis where they looked at different types of exercise in effect on cognitive function and actually only coordinated exercise. So yoga, zumba, dancing actually significantly improved cognitive function. So challenging the motor vestibular system, challenging your balance seems to be really important for cognitive function. So I'm just wrapping up now. This, again, goes back to preterm birth to kind of support that. But if you look at babies, if you look at adults born preterm, those who had better executive function were the ones who had better motor skills rather than ones who had better cardiovascular fitness. So these are the forces hastening your neurobiological demise, all scripted learnings in childhood. And then basically you go to work, you do the same thing again and again and again, and then you never challenge your neurological system. And adults also don't like doing stuff that they suck at, but you should. And so I did want to quickly bring up something that came up in Dale's talk, which is that he said that in dementia, demand exceeds supply as the brain can no longer maintain itself. But I would argue that it's the other way around. So you reduce demand on the brain and then the brain's like, well, I don't really need to be here, so I'm just gonna slowly pair myself back and saving energy. And we do know that neurons have a self-destruct mechanism. It was discovered about 10 years ago. So if you reduce or get rid of the connection to a neuron, it's just gonna kill itself. Cause it's like, well, I'm not useful anymore. And if we relate this back to muscle mass, we know that the first rule of building muscle is progressive overload. You challenge the system as it adapts, you challenge it more. And then obviously sleep and recovery, super important here, you can get a chance to talk about that. So this is basically the idea is that as we reduce demand, we reduce repair, it increases biological degradation, decreases capacity in a feed-forward loop. Instead, if we increase demands, then we can reverse that whole process. So what does a brain need? In summary, I think we should do is the babies do challenge yourself continuously, do things you're bad at, eat fish and animal-derived nutrients, move and accrue and keep as much muscle mass as you physically can and don't have a fixed mindset about having a fixed mind. Your mind is actually much more plastic and flexible than you have been told that it is. Thank you very much. Yeah. So we have some time for questions. Hey, Tommy, great talk. Thanks. So I'm very interested in what you were talking about with the ox lambs, oxidized linoleic acid metabolites, right? Yeah. Now, were you talking about them in the context, like the testing, were these from biopsies, like they were intracellular? So there was two different sets of studies. So in Alzheimer's disease patients it's just circulating ox lambs. But in rodent studies, if you increase linoleic acid content, that increases linoleic acid in the brain, which then turns into ox lambs. If you just feed ox lambs themselves to rats, it doesn't end up in the brain, but it does still decrease the amount of DHA that's in the brain. So there's two potentials. So linoleic acid may directly compete in some way, then also its breakdown products may also reduce DHA in the brain. I'm not used to an unmodified metabolite competing with an oxidized metabolite. What's the receptor involved? Or do you know that? I don't know. Okay, interesting. Thank you, Tommy. Regarding the particular skills or brain function that you might be able to gain by picking up a new skill, I'm curious as to the cross effects so let's say that you decide to challenge your brain one day by playing the flute, which you've never done before. Does that translate into necessarily skills in other areas? Let's say would it make you a better driver, for example? So I don't think so, but the process, so if you think about the newer transmittance in the parts of the brain involved in that process, so if you're actually trying to learn the flute rather than just blowing on it and realizing you can't play it, but if you're actively trying to learn it, then some of the things that you need like you will activate the sympathetic nervous system because you're frustrated by your failure and that will create some of the things required for plasticity. So doing that, you could then apply it to something in the immediately afterwards and see benefit in terms of learning that skill as well, but just learning one skill won't necessarily make you better at another. Does that make sense? Yes, yes, thank you. Hi Tommy, great talk. Real quick before my question, I think the mechanism with the OxLams is the lipid peroxidation products impair the Delta 6 desaturated enzyme. Oh yeah, that makes sense. They've shown that by feeding heated oils to rats. So my question is if I wasn't misinterpreting the graph of fat-free mass index, it looked like a U-shaped curve where you didn't want to be in the top 50%, you wanted to be at the 50%, so I was wondering if you could comment on that. Yeah, so if you're in the top 50%, actually it looks identical to the second quartile in terms of this other paper that came out that didn't show the actual amount of muscle mass. The interesting thing, and it's particularly because of the NHANES dataset, it's an average US population, the muscle mass is directly correlated to fat mass. So basically the people who have, so there's interacting and confounding factors there, that you basically, because they're linearly correlated, you can't fully adjust for that. So you think if you were able to create like some index that included leanness, then you think that just being in the top 50% it wouldn't be a U-shape. It's not an index of leanness, it's if that data were at eight. If you limited it for the model. Yeah, so yeah, you say that. If you look at, so I try to look for somebody who has my body composition in NHANES doesn't exist. So there's not even one data point that I could use. So I don't even know on a population level what body composition is best because that data doesn't exist. But you suspect in a hypothetical population of lean people that fat-free mass index would not be U-shaped? Yes, absolutely. Okay, thanks. Hi Tommy, great talkers almost. Can you tell me, is the brain training part being put into practice anywhere? So for example, are you talking to Dale? I interviewed Deborah Gordon recently and she's a co-author on the new precision medicine approach to reversing Alzheimer's and it looks great, but I noticed they're still taking the leumocity, Sudoku type approach to brain training. I think you've got something far more compelling here. Yeah, so they use brain HQ, which does have, and the reason they use it is because there's scientific evidence to support it. It does show benefit. I guess my main argument is that there's only, it's not a relevant skill in the real world. So I'm sure there is benefit because you're creating a neurological stimulus, but I would argue that getting something to do to do yoga or slacklining or something like that will give a much bigger stimulus. So I know why they're using what they're using. There is definitely benefit. It's scientifically validated, but I think there are other things that would provide a better and more important stimulus. So if you could publish data on this, then maybe then employ health coaches to teach people how to do this rather than just giving the money to some software thing. Thank you. Thank you, Tommy. I'm so excited that you and Josh are collaborating on this subject. His, the demand-driven theory of cognitive decline was like my favorite thing of the last Physicians Conference that I was at. And what I especially like about it was the suggestion that teaching might very address the multi-generational energy management concept that teaching might provide a cognitive demand load somewhat along with learning that across generations is gonna be part of our energy management system. So I didn't see you mentioned teaching in here and I just wondered if you could speak to that aspect. I think I may have skipped over it. Or maybe I took it out. There is, I did have a slide where teaching was given as an example of a neurological stimulus that provides the same and kind of support some of the aspects of the grandmother hypothesis, certainly. And there is some anecdotal data again from long-lived populations who live a long time without a cognitive decline that like those who have good cognitive faculties late into life have some kind of teaching role in society. It's anecdotal, but absolutely I think teaching is very important. Yeah, you had the arbitrary units of cognitive demand and I was just curious like if you have a sense of where they stack up. Oh no, they're arbitrary for a reason. Well, no, I mean, is it like, do you think that teaching is somewhere like on the same level as learning or like ish? Yeah, so I mean, my guess is no. My guess is that adults will really struggle to do anything that's as difficult as learning how to manipulate a flesh sack in 3D space. But I think you can definitely get enough of a stimulus in order to get the maximum potential benefit. Oh, nice last point. Thank you, cool. Okay, we have six minutes for our break so let's thank Tommy Woods again. And don't go far. We have our last trippy talk coming up very soon.