 Our next presenter is Skyler Tanner. Skyler is a partner and personal trainer at Efficient Exercise in Austin, Texas. Skyler has done over 30,000 personal training sessions. It's a lot of counting, man. That's a lot of counting. And one other interesting fact about Skyler is his favorite movie series is actually the Fast and the Furious. So if you ever see Skyler in any type of moving vehicle or especially playing music at high volumes, then get away fast. So he's crazy. All right, welcome, Skyler. So I want you all to look around and just look at the collective level of health in this room because you're not likely to see this again anytime soon. And it, well, Berkeley is kind of an exception, lots of walking. I'd also like to thank James and Jamie. Inadvertently, we're kind of the muscle militia this morning, James talking about our past as far as resistance training and trying to put this together with an idea of evolutionary fitness. And then, James talking about the public health implications of just not using our largest endocrine organ. What I'm gonna talk about is how we as researchers and human beings going forward can leverage this resistance training to maintain our most vital organ, our brain. And it's only our most vital organ because as wonderful as the heart is, touching a little bit on what Jamie talked about, it's a bit of the Kim Kardashian of the human body. It gets far more attention than it generally warrants or deserves. It's a four chambered pump to quote one of my exercise physiology professors. We've made artificial versions. Good luck making artificial kidney anytime soon. So what I'm gonna talk about with this is how early works as far as the history of exercise science as it pertains to this dichotomy of cardiorespiratory training and resistance training. Then I'm gonna dig a little bit into the putative markers of the ways in which we attempt to measure our brain capacity and brain function. Some of the interventions that have been done and then some future research directions and some practical suggestions. So what we have is, this is a quote from good old JFK back in the 1960s. I'll give you a moment to read it. But the main wonderful point here that he touches on is that the relationship between the soundness of the body and the activities of mind is subtle and complex. Much of that is not yet understood. And this is really, really true because even though historically exercise science, just for the sake of demonstration, since about 100 years old, there's some evidence to suggest the exercise science, kinesiology, which is a branch of exercise science or a component of it. In writings of 1500 BCE, very long time ago as it pertained to health. Kind of moving alongside the exercise science component is this public health science element and the two don't really even attempt to meet until the 1970s, late 1960s or the 1970s. 60 years as far as exercise science started, we start to see population studies where we're looking at the volume of exercise as it pertains to, or physical activity because exercise and physical activity aren't the same thing. We look at physical activity as a measure of health and disease markers after the fact as a measure. Behavioral science, which is a little bit of the perversion of these population studies. And then when we talk about environment and policy, we're not talking about ecological, we're talking about a bit of the behavioral economist idea of how can we create an environment that results in more spontaneous movement and hopefully better health outcomes. So this is a bit of the drunkard's walk of research as to why we end up with a lot of cardiorespiratory activity focused. It's because that's where we could see in early exercise science. It's the drunkard's problem. Why is the drunk looking under the light for his keys even though he dropped them two blocks back in the dark? It's because that's where he can see. So what happens in early exercise science within the past 100 years is you could put a person in place. You could stick a mask on them and in this case Harvard Fatigue Lab 1938, you had the Douglas bag on the left. It's that cylinder there. And then researchers would go in and actually measure the difference between sedentary expired O2 and CO2 versus metabolically active exercise levels of CO2 expired O2 expired. And we had an understanding of base metabolism so we can determine the effects of endurance type activities on these outcomes and health. We didn't really look at muscle. Muscle historically was this, you get muscle bound, you get slow. You're gonna end up being a dummy for doing resistance training. And who could blame them? Because at Muscle Beach they were doing crap like this. Fun fact, fun fact. Right here, that's Jack LaLaine. Jack LaLaine way back when. He died at 96 of pneumonia and not that, I'd say that's a pretty good way to go if you're a 96 year old guy because that kills like 12 million or a three million 12 year olds every year. So that's a pretty tough old man right there. And he sort of lived what we talked about, a good amount of resistance training, a sort of seasonally appropriate whole foods type diet. And every year would try and do something ridiculous towing boats in the harbor of San Francisco with his hands cuffed together and things of that nature throughout his old age. So that's kind of that base historic context. We don't really start looking at some of resistance training as it pertains to brain structure and function until we start to look at the loss or the prevalence of Alzheimer's in increasing in America and really around the world in general. So early work in resistance training as it pertains to middle age and older, not just athletes comes after in the 1980s after we start to focus on exercises that pertains to health and a public health sphere. So there's this idea that these adaptations were thought to be due to practice, a practice effect, an innervation effect, a neural effect rather than changes in muscle mass. So it's a bit of what Jamie was talking about with you have this muscle and the nerves are, they're big dummies when it comes to the nerves and people are just getting better at contracting the tissue they had but it was thought that they didn't have the ability to add muscle tissue. Researchers at Tufts University in the USDA's Human Nutrition and Performance Laboratory blew that out of the water. They showed that muscle mass gains readily occur and quickly occur in individuals deep into their 90s. And on top of that, they showed improvements in HDL quantity. They saw improvements in balance because that fast twitch element is the first line of the fence in balance. We think of balance as this sort of amorphous thing like here's my balance, you know, and it's not. It's a rate of reaction from the nervous system with your proprioceptive, the sensitivity of proprioceptors and the ability to create enough force to write you. And that comes from fast twitch fibers and that's why in the literature, resistance training and strength in general most strongly correlates with balance in older individuals. So that's kind of, you know, bone marrow density VO2 max. These are the things I basically talked about and there's some merging evidence that resistance trainings affect on blood markers on HDL is not more, but improving the quality of the HDL as an antioxidant. So the number doesn't change, but the quality of the HDL changes. This is still merging stuff, but it's very exciting. And so this is from a book called Bending the Aging Curve and it talks about muscle wasting within activity over time. So if you were untrained, you see it about 50 years there, you start to slowly fall off the cliff. And if you started training in your middle age, that element would slowly write the ship. So if you reach 90, if you kind of draw the line, if you reach 90 and you start training in middle age, you had the muscle tissue of about a 65 year old and that's pretty good. And it's theorized, although those slides that Jamie showed are evidences amongst the triathletes, that if you could train over a course of a lifetime, by the time you got to 90, you're probably at about the muscle mass of an untrained 50 year old. The problem with this is it's a perfect world, it's a Lake Wobegon, everybody is in fact above average. But what happens is in middle age, you'll injure yourself. This is from Douglas Patton Jones, who's a researcher at UT Medical Branch and he talks about how people will incur these injuries in middle age and they won't recover all the way up to what was their previous baseline. One of the things I like to point out to people is when it stops hurting, you're only halfway recovered. You are not in fact all the way recovered and so they will then get kind of almost there and then incur another injury, they're older, they're less adaptable, they lose more muscle mass and this endlessly repeats if you're lucky all the way to 90. So these are very easily visible things nowadays. That's part of the reason why it took muscle mass and muscle tissue as a research subject so long to come along is it's harder to measure. You could measure the metabolic byproducts I showed you back in the 1930s of endurance type activities, but you can't measure changes in muscle mass unless you're using a needle biopsy and that doesn't get used until the early 1960s. So there's this lag time and then when you're trying to secure research dollars you have to show the likelihood or the possibility of these things of an intervention you're proposing based on previous research and so you just need time and people who are getting research dollars and doing small experiments to eventually propagate into these larger experiments. So what this ends up looking like is this book Spark which is a fantastic book by the way. This was published in 2008 and I believe, am I correct in that he's spoken at AHS before? Is John Raddy has spoken at AHS? Anyone know? No, nobody knows. It seems like I'm dogging on him but he only makes one reference to resistance training in the book and that is to say that there are small studies that show mood and anxiety improvements with resistance training in middle age and older individuals which is a measure that we look at when we talk about cognitive functioning. But nothing else and he's right because at the time, I mean six years ago there wasn't a ton of data. There were some animal studies and there were some early kind of exploratory studies. So all the stuff I'm gonna show you today has come in the last six years. It's been very, very exciting. And frankly, I'm surprised it hasn't started happening sooner because if you look at this Alzheimer disease rate over nearly a 20 year period and this is CDC data, you see this 398% increase in the death by diagnosed Alzheimer's disease. Alzheimer's is a form of dementia and to put that in perspective, yes, the United States has grown significantly. The 65 and older population has grown about 28% in the same period of time whereas the total United States population has grown about 24%. So it's disproportionately higher now, could that be because of improved diagnosis? Maybe, maybe, but you would think that it would be a smaller number and what happened is this is a bit of the effect of the boomers which is there's also evidence to suggest and this comes out of the study in the journal of the AMA Internal Medicine which is boomers will live longer than their parents but the onset of debilitating disease is happening sooner. Thanks, pharmaceuticals. You know, I mean, and so that's what, it's just gonna plod you along is this sort of amorphous troll in the wheelchair and without your mental faculties. So why is this important? So why am I talking brain? Well, mild cognitive impairment is an early, early indicator of later dementia. 30 to 50% of mild cognitive impairment cases will turn into dimension. It doesn't sound like a lot but you have to also look at the studies that have been done. They're typically 10-year periods and they all conclude the older you are, the more likely this is to happen and that the younger you are in this 10-year period, so if you go from 50 to 60, your mild cognitive impairment doesn't turn to full blown Alzheimer's or any other form of dementia. Well, give it time, right? There's a time scale involved here. So you can get ahead, if we could get ahead of it somehow and reverse the mild cognitive impairment, we reduce that risk even lower for possible dementia or this wonderful statistic right here. Let's move on to the putative markers and assessments, so I like to point out that there's a difference between measuring things in the blood and then measuring how a human actually interacts in the real world. So putative markers are the blood markers and we'll start with those because you start with the animal studies and then you move to the human studies. Vascular endothelial growth factor, veg, it's this wonderful protein that is secreted in the periphery by muscle tissue that has been pushed into a hypoxic environment. So going to fatigue or very close to fatigue is something that James was speaking about earlier. You end up having this VEGF in the interstitial that moves in the central circulation and it ends up affecting the brain. And then in animal studies and in human studies this correlates with maintenance of gray matter volume, hippocampal volume and that generally correlates with cognitive function and I'll get to that all those correlations here in a few minutes. But when you look at it, when we talk about this, this is kind of a nice easy layout of why that's important. So exercise antidepressants in an enriched environment which when we talk about little rat studies is are they in an empty cage or are they in a cage with the shiny wheel and wonderful little obstacles to climb on and generally an environment that promotes going back to that behavioral model that the behavioral economists are talking about promotes spontaneous physical activity. That's an enriched environment in laboratory terms. It increases this vascular endothelial growth factor which leads to an increase in endothelial cell and neural stem cell proliferation. This results in neurogenesis which is the creation of new nervous system tissue. Something that up until very recently they thought was just didn't happen and we've seen that you can in fact grow new neural tissue in the brain and elsewhere in middle age and above, middle age and above. It happens quite readily with a sufficient amount of intensity. Now chronic stress and aging as you see here results in a reduction in VEGF and then a reduction in this neural stem cell proliferation the exact opposite of what we want. The next is another protein that everybody seems to maybe be a little bit more familiar with this brain-derived neurotrophic factor, BDNF. It is the one that is most cited in the endurance type studies. It's the one that is most often looked at as far as its ability to increase this interaction at the neural junctions where the action potential and the crosstalk between neurons and other portions of the brain are occurring. When this goes up that is seen to improve in these animal models. And again that correlates, BDNF correlates with maintenance of brain mass, brain structures throughout aging. And then beyond that though it correlates with other things like reductions in BDNF are associated with obesity and type 2 diabetes and cardiovascular disease. Never mind the cognitive impairment dimension, depression that are part of this neurocognitive, the neurocognitive things I'm discussing today. So very, very important. And it seems it's in the endurance studies it's the prime measure or often the prime measure because it readily it's the one that gets driven up highest. But it's not the only one. VEGF is one. And then on top of that our old friend insulin-like growth factor. Now the paleoprimal community, ancestral health community has a real ridiculous love for growth hormone. Growth hormone's a hyperactive child. It goes up no matter what you do. Starve a little bit, growth hormone goes up. Feed, growth hormone goes up. Exercise, growth hormone goes up. Don't exercise, growth hormone goes up. What you care about is IGF-1 because IGF-1 is the enforcer of growth hormone. It is what actually carries out what growth hormone wants to do in the body. It is the long arm of growth hormone. And insulin-like growth factor we've known for a really long time is what resistance training drives up readily. It pushes it up very aggressively and because it's intensity, it's intensity derivative. If you have a high enough intensity, IGF-1 will go up. Lower intensities, it just doesn't happen. So in the neuroscience literature these are called angioneurins which means they help to increase the proliferation of the creation of new blood vessels in the brain which is also very important and it also increases in nervous system tissue. Now this for a nerd is all very shiny and very wonderful and I just, oh it's so pretty. But the important points are in the bottom. So this BDNF is a survival factor during neurodevelopment. It's also associated with neuroprotection, neurogenesis. VEGF leads to angiogenesis. IGF-1, angiogenesis, neuroprotection. And then this third guy, or this fourth guy, the TEGF-beta-1, he doesn't really matter. No amount of evidence I could find in resistance training studies looks at this at all. It's totally a secondary marker but in the case of, it's still classified as angioneurin in this data. So human studies are incredibly cutting edge in this stuff. Like I said in that 2008 book, you got to think about the publishing tale. He probably finished writing his book in 2007 before it got published. So the earliest studies with humans, 2007 showed increases in vascular and ethereal growth factor and brain drain of neurotrophic factor in middle aged and older humans. Acute and chronically due to resistance training. And IGF-1 seems to potentiate this process and I'll talk about this a little bit later. But it doesn't matter the age, the rate of response in older individuals is similar to younger individuals assuming there was enough intensity, assuming you worked hard enough. The result was very, very similar. So these are the nice markers, right? You put in the stopcock, you do some acute training, you take some blood measures, you see, ah, BDNF went up, BGF went up, IGF-1 went up. So what? Why, so what? Why does that matter? And this is an important point because what you really want is that to somehow correlate with our ability to interact with one another and maintain our mental faculties throughout aging. So there are studies that have demonstrated that plasma BDNF are indicative of slow white matter volume reductions with aging, but have nothing to do whatsoever with cognitive performance. They just don't correlate very strongly. And I'll cover that a little bit later when I talk about FMRI studies. So what we have to use is things that are called neurophysiological assessments. So these are cognitive functions that are used like the strupe test or these digit forward, digit backwards. And we're all gonna do the strupe test here in just a second. These are used to measure executive functioning, how well we can discern information, how well we can utilize the environmental inputs and actually make sense of it all. And this is important too, because it directly associates with, to some degree, the hippocampal volume of our brain. So the hippocampus is a bit like the librarian of the brain. It sort of shuttles things in the short and long-term storage and then can reliably call it back when you want it. And if your executive function is ports, generally correlates with this reduction in hippocampal volume. So what I want you to do, we're not gonna do every row, but I want you to sit there and as quickly as you can state the color of the boxes. You don't have to yell it out, but just, I'll give you a second, just quickly go box one. You know, you'll go red, blue, green, yellow. Not a problem at all. The next slide I'm gonna reiterate. Say the color, not the word. What's gonna happen is you'll read the word. You'll go red, no crap, green, yellow, blue. And this is an incongruent stimuli. You will want to read the word and you will have to take a moment to differentiate between what the meaning of the word is and what the color of the word is. A lot of these tests are what that, you've seen Lumosity advertised all over the place. So what they've done is they've taken these assessments and turned them into games with the assumption that if you get better at the games and you're getting, then you're actually improving your functional capacity, this neurocognitive function. And it correlates really, really, it works great in determining if one's function is improving in the real world as we age. So those are the tests that we're really looking at in human trials. Interventions and outcomes. Up until about 2012, there had been isolated studies where resistance training had been done for determining improvements in cognitive function. Plenty of cardiorespiratory studies on improvements in cognitive function. But never the two shall meet in a direct comparison. But in 2012, researchers in British Columbia actually did a cardiorespiratory versus resistance training comparison. This is my grandma with my son earlier this year. Now, she's 86. She's had a couple TIAs, which are these mini strokes. And she's so funny about it all. She'll lean in, she'll be like, I've got a bit of a memory problem. If I repeat something, don't, I'm not offended if you tell me that I did that already. And then she talks about these community-dwelling women. Because she's a community-dwelling woman. She lives in an adult resort, which she thinks it's hilarious, she'll tell us. They call it an adult resort. They left out a word. They should call it your last resort. You're hanging out and you're having dinner with someone and then over the weekend you don't see them. You think, hey, their family came to get them? No, they died. Word for word in what my grandma said. So she thinks it's all very surreal and kind of crazy. But, so 86 community-dwelling women, aged 70 to 80 years, twice-weekly resistance training, about a half-hour pop, versus twice-weekly cardio-respiratory training. After six months, the resistance training group matched or exceeded the aerobic, or the cardio group, results in a number of tests including the primary measure of the stoop task. Now, the one in which they did not improve nearly as much was the six-minute walk test, which is a sort of a field test of function. Well, yeah, they weren't walking on a treadmill. There's a skill component in anything you do. If you practice walking on a treadmill, you're gonna get really good at walking. And so they didn't improve as much in that, but they did improve nonetheless. So this is the tip of the spear. In addition to, if you have a group of individuals who are otherwise sedentary and they're not going to participate in too much activity, wouldn't you choose the activity that has the largest number of upsides? If we, going back to that hard thing, we're so obsessed with this, that doesn't matter how great your heart is if you can't get up out of your chair. But that's what we end up with with the stretchy bands of purple color and sort of laying over in the seat like a halfway-dead person, when really what we want is to be able to somehow direct our lives physically and mentally for as long as possible. And if you have a family and you have a job and you have a career, you have responsibilities, then you are going to pick the task that gives you the greatest upside for the lowest amount of input, and that's resistance training, as is being demonstrated again and again and again in the most recent studies. So we have to talk about, in the future, though, what are some other measures that are coming out that we can use to determine if a resistance training study in older individuals is going to be beneficial? So one of the things I mentioned earlier, I talked about FMRI, but only very briefly. And the reason being is that, here's an example of a before, on the left, and after in a resistance training study. This increase in the activation, these blotchy patterns of red indicate an improved amount of cognitive functioning and voluntary control after resistance training trial. The problem with functional MRI is that as fine as it is, it's not fine enough. There's a study done 12-month resistance training program in 70 to 80-year-old women. As measured by StroopTask, they had a 12.5% improvement in function, but it's measured by FMRI volume, gray matter volume, I know, white matter volume in the study. They lost half a percent of volume. So what gives? If you're looking for a volumetric measure, then clearly resistance training is terrible. The problem with that is that it's not a fine enough measure to determine things like fluid shift, protein changes. So what you're probably seeing is just a noise. You're seeing the difference in noise on that given day. And really what I would like to see, and it's just cost prohibitive, you'd have to take an FMRI every day. It's a bit like a blood marker, right? Let's take your cholesterol, right? Take your cholesterol. Okay, take your cholesterol a year later. Is it different? Probably. Well, your doctor will then, if they run the sort of standard, oh, you're over 200, we're gonna hit you with the statins or have it sit you down for the talk. The problem is is that it's a bit like trying to determine the plot of a movie from a frame of the movie, right? All right, here it is, tell me about it. But that's what we attempt to do. We look at one isolated measure and then attempt to extrapolate a huge story from it. When throughout that year, they could have had more mass, more less mass because of just this fluid shifts. And you see this in Alzheimer's medication studies too in pharmaceuticals. Huge improvement in function, loss in brain volume. As these get more and more sensitive and it becomes less cost prohibitive, and that's largely been the problem with resistance training studies is you need sensitive measures or measures that are like, we're gonna take a core sample of your thigh with that giant needle. You don't get as many people on board for that. And since no IRB board so far is gonna let us do brain biopsies of living humans yet. Any really low level research universities wanna try this, I'm sure you can recruit some people. This is what we have to kind of run on as an MRI. And so as it gets better and better and the Tesla coils become even greater and it can see into the future because of its sensitivity. We can then rely on it a little bit more, but it just more informs a little bit of the conclusions in the real world. This is interesting though, MRA, Magnetic Resonance Angiogram. Now, Angiography, what it measures is the, you can see these are all the arteries going up into the brain coming off of the heart there at the bottom. And you can see some of the veins as well. But what it's looking at is the amount and the tortosity, which is the straightness, the superhighway likeness of these vascular structures. So you want as straight as possible. You don't want it to look like the 101 at its most giant is flowing this point. You don't want it to look like a back country road going back and forth like this because the amount of blood that can be summoned to the area is reduced as a result of that. And there's a study that's been done. I'm gonna call your respiratory study that they did this image and then they did a questionnaire. It's like, okay, well, do you do high intensity or low intensity or low volume, high volume cardio work? And based on that answer, yes or no, those who said yes, they had these beautiful, beautiful vascular structures and those who said no, didn't. Okay, well, that just tells us did the vascular structures precipitate into more activity or did the activity precipitate into better vascular structures? We don't know. And this type of research needs to be done in order to determine what exactly is going on there. Is it the activity or is it the actual structures that precipitate the activity? And so there's some animal studies that elucidate some of what I talked about earlier. You heard me say I'm gonna get back to IGF-1. I'm gonna get back to VEGF. Animal studies have actually done resistance training studies in rats. And what they do is they will hang some weight from the tail. Typically 50 to 100% of the rat's body weight. They will do laps up and down a ladder. And then they'll kill them and they'll do brain biopsies. And then they'll compare that to rats that have just done sprints in a wheel. And what happens is that those rats that did the cutter respiratory focused work, they end up having a significant amount of BDNF increase. The rats that did the resistance training had a significant amount of IGF-1 increase. But when you tore those brains out of their little tiny skulls and you looked at the size of the hippocampus and the amount of the brain volume, nears makes no difference, they were the same. And this is where I bring it back around to an ancestral perspective. The human body is complex. It is also incredibly redundant. Any attempt to attempt to find a singular answer is a fool's errand, number one. And number two, your body is very good at determining an outcome through multiple avenues. So the IGF-1 that resistance training produces acts as in fact a lever. It acts as a force multiplying mechanism for the amount of BDNF and VEGF that it produces. It doesn't produce as much as cardiorespiratory endurance type activities. But without the IGF-1, they can block IGF and the periphery. You don't see the increases in these animal models in the size of the hippocampus or the maintenance of gray matter and brain volume in general. So what resistance training does is the IGF takes a little bit of BDNF that it produces and a little bit of VEGF that it produces or moderate amount, it's not tiny, it's not insignificant. And it force-multiplies that. When the IGF-1 is gone, then they become paltry amounts. So if your measure is it has to be this much BDNF because that's what the cardio study says, that totally leaves out the fact that we're incredibly redundant and other molecules can leverage the effect of some of these markers that we look at, that we traditionally look at. So IGF-1 is tough stuff. It also makes any other change that we have by any other marker much, much better off. So what's the prescription, right? So we've talked about this a little bit of a sufficient intensity. Man, I'm gonna burst everybody's bubble and say, no, that's exactly what I'm gonna say. It's all about the intensity. But it doesn't have to be complicated. A paper published in the past couple of years discussed uncomplicated resistance training for public health. You don't need to have a conjugate drop set phase of the moon kind of training program that's auto regulating your auto regulation based on your astrology sign. I'm a Pisces, so I have to do undulating periodization with plastic coated weights and a Fran on top of a Julie on Tuesday. Right, if you're a super athlete and you have an Olympic medal or a paycheck on the line, these tiny, tiny percentages of possible improvement, this cutting edge of sport signs, matters very much. Or from my colleague Keith Norris, it for some reason matters very much. But for everybody who wants to use this, whose dogma and purpose is not to be an athlete, to be athletic, there's a difference. It's a bit like the book title, Born to Run. No, you are born with the ability to run. You don't have to use it unless you want to. It'd probably be a good idea that you can. And so from a health perspective, here's what you do. Six to 12 exercises, two to three sets per exercise. Now, that can be different exercises. So if you don't want to do 14 sets of bicep curls, nobody does. You just pick different exercises. Maybe it's a row and a pull over and a pull down, one set to fatigue each. Typically we want to see 70 to 80% of one repetition maximum. This correlates roughly with an eight to 12 repetition max. In these studies, the women, little ladies were going to technical failure, means they could not lift the weight again in good form. They would have to use a lot of body English in order to accomplish that. And that is the intensity component, that high, high effort. You want to progress this over time, but it's not as nearly as important as the attempt to work very hard. You'll see acute changes. Do a training study, measure the blood before and after an improvement. You'll even see changes do a strupe test before and after. And not after immediately, because you want to blunt that learning effect to some degree, hours after on the same day and they'll have a better strupe performance. But at least four weeks of training is required to see more permanent results in so far as these changes in structure and function. And it doesn't take a lot of time. Like I said, two to three days per week, if it's taking you an hour, you're doing it wrong. It doesn't, because the intensity is important and intensity by necessity requires a lower duration. So that is all I have. Any questions? You can't have any more questions. Downsides from too much IGF-1? Oh yeah, I mean, here's the problem is if we're, Merca, the problem with Merca is that if a little is good, infinite must be better, right? Like a tiny bit of unfermented soy, great. But then when it's soy suppositories with your soy milk and your soy sunscreen, then you get, then you're a dude becoming a lady because of all of that phytoestrogen, right? So the downsides, yeah, there are downsides. And, but resistance training does not drive IGF-1 into ranges that are considered problematic. It's attempting to keep it within normal to high normal ranges, right? It's like testosterone. Testosterone doesn't become a problem until it gets pushed to supermaximal ranges. Then, since it's androgynously, or extrogynously provided, then your testicle shrink, right? But until that point, everything functions in normal because it's in normal range. Thanks. That was a really, really amazing presentation. So thank you. So you said a bunch of times that you had to do enough exercise. Is that because there's a threshold effect? Because it seems like that prescription was relatively mild and I would have expected a more continuous kind of function, not like nothing, and then, yeah, you got something. So when you look at a dose response relationship of exercise in general, you can get a very high percentage of the effect from your earliest inputs. So, for example, if you look at the CDC data on all-cause mortality, it's the first 45 minutes of physical activity a week that it's the sharpest decline in all-cause mortality. And after that, it gets flatter and flatter and flatter. This is a bit of what I touched on at the end of having enough of an intensity and making sure that it's part of your life. What tends to happen, though, is people will confuse physical activity and exercise, they're not the same thing. Exercise is directed and it has an appropriate measure that you're attempting to improve over time. I talk about exercise as a foundation in which you can build whatever house on it you want. But the poorer the foundation, the less opportunities you have for that house that you're building. And then on top of that, exercise directed, measured exercise precipitates increases in physical activity. And it does this because in a literature, when this comes out of health education, which is really interesting, not exercise physiology, the stronger people feel, the better they feel, the more they do at these activities, the more they do these activities, the better they feel about doing those activities. And it snowballs, and it snowballs. But enough exercise is more about sufficient frequency, which isn't all that much, sufficient intensity, which is higher than most people are willing to push themselves, even though it's not that high. And time, like not getting caught up in the details of having a good workout or a bad workout this week, some of that auto regulation effect, if you were here for James's talk much earlier, we talked about if you go in, not feeling so great, take a day, come back tomorrow. Your body doesn't operate on the strict calculus of you've been, it's been 72 hours, but you've otherwise been active, you're gonna lose all that muscle mass. It's gone. It's much, it's a signaling agent. Resistance training is signaling that all these things are important. It's a dose response relationship. So enough is intensely. The more intensely you do something, the less frequently you do it. But what that precipitates is a lot more physical activity throughout the rest of the week. Most people get it backwards. Like it's the whole biggest loser thing. They're fat because they work out, or don't work out. No, no, they don't work out because they're fat. They don't feel good. There's no amount of intrinsic reward for that movement. And so that's, we tend to flip that. We gotta move a lot at a low pace. But you move at a low pace when you're fit because you can't stand still. And just to follow up, how do you determine intensity? So without having, which is a great question we had earlier, traditionally labs will give in on a six to 20 scale, which they just lopped off the zeros because it roughly correlated with like 60 beats per minute. I know what scale that is. But with resistance training, it's getting to the point where you can no longer lift a weight in good form. And since I gave that range just 70, 80%, this correlates roughly with eight to 12 repetitions. Uncomplicated and then come back and then when you can get to the top of that range, knock it down and attempt to gradually increase that weight over a long period of time. Muscles are very, very plastic, but building new muscle tissue out of the blue, de novo takes time. Thank you. I'm wondering if there's any evidence that doing something like training with kettlebells and doing a smaller number of exercises could achieve the same thing as the number of exercises and what you described above. Correct, correct. So what I did was I took the fat of the recommendations. Tons of study. This is my research review for my graduate program. It's like 20 pages long, right? So I took the, trying to take the cream of it all. They had individuals, women who are community dwelling doing calisthenic exercises that saw a trend association between BDNF, for example, right? So they're doing, it's still resistance training and at their level, it's here, right? If you're really out of shape, chair pushups are on the podium. This is high intensity, right? Eventually you progress to more complicated progressions. Simultaneously they had others where they were force feeding them like 20 eccentric contractions three days a week and it was just, it would kill just most mere mortals, which is hilarious that they were doing it with sort of sedentary middle to late stage individuals and they had effects but this was kind of the fat of it. The point is, is it's a, it's resistance, it's progressed. You would have to go to heavier kettlebells, right? You can't be stuck with that 35 pound bell for 200 repetitions, because that's cardio. It's what some of the people, the Brett Contrerases of the world talk about with like heavy ass kettlebells. You get up to 100, 150, 200 pounds but then you introduce an element of an element of instability, whipping this thing around and then injury risk. So then what it is, is okay, you could probably do a bit of cross training. Some pure concentrated resistance training and then your physical activity would be all that kettlebell stuff you'd rather be doing. Okay. Right, and then you won't get caught up in the ups and the downs on a weekly basis. I should be progressing more. It's like, you can focus on the process oriented progression rather than measured outcome oriented progression. Thank you. If I could hit you with one more IGF one question. Yeah, some studies seem to indicate that as IGF one goes up longevity goes down and cancer risk goes up and some particularly notable studies on centenarians and super centenarians having very low IGF and these were basically folks who engaged throughout their life in a lot of really low intensity activity like walking and gardening and so forth. So which seems to fly in the face of, you know high intensity strength training and interval training. What are your thoughts on that aspect of it? So I'm not encouraging an interval training. Just in case you got that from that, no. But what that is is you're talking about moving something from a low normal range in a medically documented situation. All these individuals had mild cognitive decline and probably mild cognitive decline. The other thing that you have to take into account with these blue zones, these long lived individuals or centenarians and super centenarians is you have a graveyard effect that you cannot observe, right? Or the founder effect is another term for this. You don't know what it is that's innate about them and so you start measuring everything and the problem is that you can lead to erroneous conclusions that it's just the low IGF one. It's a bit like there's a lake in Northern Italy that was largely isolated from the rest of the population for hundreds of years and when researchers finally got in there and found that the heart disease was almost zero it was paradoxical because their HDL levels were also almost zero. What's the deal? Well they had a genetic mutation that basically eliminated through the narrow breeding of the area the heart disease risk through an entirely other process that is an APO protein B I wanna say. Don't quote me on that though. And so what happens is if you go in with looking at just IGF one and you don't have the ability as I kind of talked about the ability to measure these other things then you're only gonna look at that one thing. I don't, this is not driving it to super maximal levels. It's normalizing levels that are otherwise depressed in these elderly individuals. Yeah, apparently the secret recipe seemed to be low IGF one, low insulin and low CRP. They all seem to have that in common. Yeah, inflammatory markers being reduced are definitely the case. But again, IGF one is the long arm of growth hormone. It is what facilitates all the good things that growth hormone does. So if it's excessively depressed then growth hormone is not capable of doing everything that it does. So you don't think it necessarily accelerates growth of cancer cells then? I think that's outside of my realm of expertise. Yeah, I'm talking about the brain, dude. Okay. Well, thank you very much. Let's give Skylar a hand.