Barbell Shrugged - How Lifting Weights Affects Your Genetics w/ Dr. Kevin Murach, Anders Varner, and Doug Larson #748

Episode Date: May 22, 2024

Kevin A. Murach, Ph.D., received his undergraduate degree from the University of North Carolina at Chapel Hill, where he earned the Ronald Hyatt Scholarship in Exercise Science. After graduating, Dr. Murach completed a master’s degree in Exercise Physiology at James Madison University at Harrisonburg, Virginia, then earned his Ph.D. in Human Bioenergetics from the Ball State Human Performance Laboratory in Muncie, Indiana. His dissertation was a collaboration with NASA aimed at optimizing the exercise prescription for astronauts on the International Space Station. After Ball State, Dr. Murach spent six years as a post-doctoral fellow/scholar at the University of Kentucky Center for Muscle Biology in Lexington under the guidance of Drs. Charlotte Peterson and John McCarthy. During this time, he was supported by two National Institutes of Health grants (F32 and K99), was recipient of the Thomas V. Getchell Memorial Award from the University of Kentucky Grant Writing Workshop, won the 2017 FASEB BioArt contest and was an NIH NIA Butler-Williams Scholar.He now is an assistant professor in the Department of Health, Human Performance and Recreation in the University of Arkansas College of Education and Health Professions. His current research uses human muscle samples, primary cell culture and genetically modified mouse models to understand the molecular cues that drive exercise adaptations and aging, and the interaction between these two (among other things). In his free time, Dr. Murach enjoys spending time with his wife, Dr. Kyndal Murach, exercising, building custom watches, cooking, smoking meats and collecting bourbon. He shared this preprint he recently posted: https://www.biorxiv.org/content/10.1101/2024.03.26.586857v1 Summary: This study investigated the molecular mechanisms underlying muscle recovery after exercise, focusing on the temporal dynamics of gene expression and DNA methylation. Biopsies of the vastus lateralis muscle were taken before and at various time points (30 minutes, 3 hours, 8 hours, and 24 hours) after resistance exercise (RE), along with a control group. RNA sequencing and DNA methylomics were employed to analyze gene expression and methylation patterns, respectively, complemented by computational methods. Work with RAPID Health Optimization Dr. Kevin Murach on Instagram Anders Varner on Instagram Doug Larson on Instagram Coach Travis Mash on Instagram

Shrug family, this week on Barbell Shrugged, we've got a special intro today, but on the main show today, Dr. Kevin Murak is coming in and we are talking about how lifting weights affects your genes. Very interesting conversation because a lot of times we just think we're gonna go lift weights. We're gonna go to the gym and we're gonna go

get our pump on, build some muscle, go home at night. But what we don't ever think about is how that affects this little thing called epigenetics and how our genetics use lifting weights to turn on and off specific genes in our body that allow us to promote that muscle growth, essentially creating an environment in which our genetics have to react to that stimulus to create a bigger, stronger, more badass you. But before we get into that show, Coach Travis Mash is on the show because, or into this intro, because he has a seminar coming up on June 1st, correct? That's right, June 1st. I nailed that. That was right off the memory. I didn't even have notes. The Forge Athlete Coaches Clinic, I think it's going to be the premier clinic for coaches in America. We've got everything covered from speed to nutrition with your boy, Dan Garner, to sleep and recovery from your boy, Dr. Chris Perry, who's been on our show.

We got, I already said speed. We've got strength with Dr. Sukumil. Of course, Joe Ken is going to be talking about movement. And then I'll be talking about how to create the adaptation you're after. And next week, just for getting our audience caught up on Dr. Sukumel, I'm going to be posting that show. We interviewed him last week on a show that probably could have been three hours long. And we went about an hour realizing, man, we need way more time than calendars currently allow. Yo, are you still having, we had him on the strength coach from the Carolina football

team. That's how much I pay attention to the NFL. Not the Hurricanes. Carolina Panthers. The Panthers. He's coming too, correct? Carolina Panthers. Yeah, Joe Cannon, he's going to be talking about movement prep.

But I mean talking about everything from breathing to the specific movement to prepare you for whatever activity you're after. It's going to be much more than a warm-up, man. It's really preparing your body to do the thing you're after. Would you recommend coaches and athletes show up to this? It's going to be much more than a warmup, man. It's really preparing your body to do the thing you're after. Would you recommend coaches and athletes show up to this, like the strength coach side of things? And then athletes just always on as a, as a goal for essentially just improving their, their skills.

I would man, because like, you know, when I was an athlete, like I wanted to understand the process. And so if you're an athlete who wants to know if what you're doing is, is, is good or is actually going to create the adaptation that you're an athlete who wants to know if what you're doing is is good or is actually going to create the adaptation that you're after i would i would say yes educate yourself otherwise you're trusting your future to somebody who may or may not be worthy of that future so so yes and i would even say parents if you want to learn about athletic performance and the potential that's in that for your kid i would say even you

too but definitely the coach out there is i think it's the only thing missing would be sports psychology i think we've got every single thing you need to know as an athletic performance coach but except the one thing but next time we'll get that too and this is going to be at rise indoor sports which i think is like maybe the most beautiful facility you know what's interesting is after coming to rise and hanging out with you for a day and seeing what you guys have built out there anytime i'm driving around now i pop into like the like all-in-one sports training facilities thinking that i'm gonna see rise and then i'm like well this is okay but it's like a b minus in comparison i feel like

i saw the gold standard on day one dropping into rise and then now everything else is like i know man i don't think i'll ever be able to go anywhere else after this you know i have to admit our uh one of our owners neil he's neil corn answer is like the on-site manager there's two others they're more silent but the the fact that these guys had the guts to build this 130 000 square foot facility in bermuda run north carolina you just got to give it off you take your hat off to those guys because it takes a lot of courage you know and we're doing well so i'm excited also got to thank jim wear for all the equipment that we have too like you know the fact that we have some of the best sports science equipment right here on

the end, you know, that's a thanks to Jim Ware as well. Yeah. The one day that I was there, some monstrosity of a human walked in and you were like, yeah, he plays in the NFL. I was like, God, can you imagine getting hit by a person that size at full speed, the freak level of athleticism that they have.

So people want to attend. Where do they go? You can go to, it's on Master Elite, but you can go to masterelite.com backslash the-forge-athlete-summit backslash. We can put it in the show notes, hopefully. Or you can link in my bio. Go to Master Elite Performance on Instagram. Link in the bio will be and um but or you link in my bio go to master elite performance on instagram link in the bio be the first thing there that's the easiest um fantastic

so june 1st when does it start it starts uh at 8 a.m it's going to be a long day so i almost thought about doing you know two days but like i want to do one awesome day and then i want to hopefully maybe spend some time with our um guests that are coming into town just alone so I can that's selfish to me but maybe take them out on the lake and just learn from them myself so I love that yeah man if you do end up attending there's going to be a very solid special guest that shows up for about eight to maybe 10 11 o'clock named Anders Varner as he is in route. He's in route to the Chris Stapleton concert in Charlotte. But it's impossible to get to Charlotte

from my house without passing by Rise. So we're definitely going to hang out a little bit. I want to say this too. If you can't make it, we're going to stream the whole thing live. And then we're also going to give obviously after it's over, we'll have a copy of the whole thing as well to the people who bought so there's three different ways even if you even if you can't get in there you can register and then get

all the videos sent out afterwards so right or watch a lot yeah or yeah exactly or come on site fantastic we'll get over to uh mash's instagram page Click the link in there. And it's the top thing in his link. The very top. And then friends, as always, make sure you get over to rapidhealthreport.com. That's where Dan Garner and Dr. Andy Galpin are doing their free lab, lifestyle, and performance analysis. And you can access that free report at rapidhealthreport.com. Friends, let's get into the show. Welcome to Barbell Shrug. I'm Anders Varner. Doug Larson. Dr. Kevin Marac, welcome to the show. Hello. Thanks for having me. You were saying, first off, James Madison University, we share that in common.

Beautiful Harrisonburg, beautiful smells that come from that dog food factory not too far down the road. Seeing all the little chicken trucks blowing feathers all over you while you're trying to drive to campus. We share that. Um, but also you and Dr. Galpin, you thought Dr. Galpin was the reason you got on the show today, but we're here to pick your brain on all things, muscle recovery. Um, and you have a brand new paper coming out that we're going to dig into. Not, not officially a paper yet, but on its way, um, free paper. Um, but I love to get kind of, of uh starting with meeting Andy Galpin at Ball State University um maybe a couple great stories of Andy doing something that he wouldn't be so proud of

anymore um but yeah really I'd love to know kind of know your path on exercise phys side of things and sure yeah yeah background we'll go back to undergraduate i guess and start there which was at unc chapel hill so i'm a tar heel first that's where i'm at right now too tar is great apex north carolina oh no kidding okay yeah well we have a lot of overlap here and so each other yeah apparently uh so yeah i went to unc it was tar heel and while i was there i studied exercise and sports and i didn't know that was a thing when I was there, you know, like that. I didn't know what I wanted to do. And then I found out I took an anatomy class. And then I was like, Oh, wow, you can study exercise. This is crazy. And what do you do with it? I don't know, but I'm going to do it. And so I did.

And then graduated and, you know, didn't 100% know what to do with my life. So I went up to James Madison got a master's degree in exercise physiology. And that's where my path changed. I met Dr. Nick Ludin, who was my advisor there. And he advised me to go to Ball State, which is where I crossed over with Andy Galpin a little bit. He was a little bit ahead of me. I think we overlapped by maybe a summer or something to that effect. But yeah, so I did four years there kind of studying, I guess, similar things to what

Andy would have studied at that time too. So, you know, skeletal muscle biopsy work. So taking muscle samples, looking at the exercise responses, single muscle fiber mechanics, and a little bit of molecular biology. So did four years there kind of looking at that. And then after that, I went to University of Kentucky where I spent six years as a postdoctoral fellow. And during that time, I got more than I guess in the weeds,

you could say I kind of started to look more into the molecular aspects of exercise adaptation using genetically modified mouse models, I studied muscle stem cells quite a bit, that was really the focus of those six years was like muscle stem cell work. And so I got really interested in muscle stem cells. But then towards the end of that six years, I started to become more interested in what's going on in the muscle fiber when we exercise, how does it know to adapt? How do those processes occur at kind of the molecular level? And I got interested in aging a little bit too, as you know, at that point, I was starting to get a couple of gray hairs and I was like, yeah, you know, I wonder, I wonder how good exercise is for this aging business. And so

I get into that a little bit more and that's kind of the focus of my lab now. So in 2021, I started my lab at the University of Arkansas. It's the Molecular Muscle Mass Regulation Laboratory. And we focus on exercise and aging. We use a lot of mouse models. Epigenetics is a major focus of what we like to what we, uh, we like to study and think about. Um, but, uh, yeah, I also have collaborators all over the world and we do work together. And so, yeah, the, the preprint that's up online that you alluded to as a collaboration

where he did a lot of the human muscle component and I did kind of the validation work in the mouse models. And so, um, that's, uh, kind of how that, um, how that relationship, uh, occurred, but, um, yeah, that, that's, of how that relationship occurred. But yeah, that's where I am now. So I've been here for a couple of years and I've got a lab, got a couple of great PhD students, a postdoc, a lab manager, undergrads, the whole thing. We have a great wet lab set up and yeah, just doing muscle science. That's the name of the game.

Yeah. Fantastic, man. I'd love to dig into this. We'll call it pre-paper here. And where did kind of like the light bulb go off that this was going to be what you're going to look into? And then I'd love to just kind of put all of this in an umbrella of muscle recovery post-workout and a lot of the things that you guys found here. Sure. Well, I'll try to tell this in a little bit of, I guess, a literary background sort of, and also put the science in context with that. So when I was a postdoc at the University of

Kentucky, I was working with Dr. Charlotte Peterson, who's a legend in the field of muscle stem cells, and Dr. John McCarthy, who's a legend in the field of also muscle stem cells, specifically muscle hypertrophy and things like that. And he, during that time, there was a visiting scholar that came over from Sweden, the Karolinska Institute. And if nobody's familiar with the Karolinska Institute, it's a very, very famous biomedical university. Well, it's a university, but also has a huge biomedical component of it over in Stockholm, Sweden. And a lot of like the OG exercise physiology studies involving invasive stuff like muscle biopsies happened over in that area of the world. And a lot of it happened at the Karolinska Institute. And so it has a really strong like historical

component related to muscle research and molecular biology and things like that. And so, but the visiting scholar came over while I was a postdoc at Kentucky and he just showed up in the lab one day, the Swedish guy, he brought his whole family over. He has four kids, his wife, they all came over to Kentucky for an entire year. He's an MD, PhD. So he basically put his practice on hold and did this year abroad over in John McCarthy and Charlotte Pearson's lab. And so he just showed up one day. I didn't know who this guy was. He's got these little like Coke rim sort of glasses on. I'm like,

who's this guy? No one told me there's a Swedish guy showing up. But we got to talking and realized that we had like, basically super similar interests. And we're asking all the same questions about muscle biology. And so so this must have, I'm trying to think when this would have been, this probably would have been like 2019. So maybe five years ago, probably five or six years ago. So we crossed paths and he being a physician over there, he studies a variety of things, but one of the things he really likes to study is exercise adaptation. He's really interested in a process called ribosome biogenesis, which, you know, ribosomes are like the construction workers of the cells. So when you exercise, you make more ribosomes in order to make more proteins in order to make the muscle bigger. So he's interested in that process in a

nutshell. And so he had done a study where he grabbed, so basically had people come into his lab and it was like eight people. He had people come into the lab and he took a biopsy. So basically I'm sure I don't have to explain this to your audience, but I will quickly. You know, a muscle biopsy needle is kind of like the size of a pen or a pencil, right? Doug had it done. Oh, there you go. Yeah. Many, many times.

At Ball State, we had a tendon biopsy done on our patellar tendons. Andy did also. I believe it was Trappy that that that did that well yeah no those are said that we were going to be fine a day later and that uh that was not true no more tendon biopsies for me i don't think they do very many of those anymore like yeah i've heard that horror story two tendons they don't heal very well so if you know jab a needle in them they tend not to heal so great so um yeah that that that's why they don't exist anymore that's right i'd much rather have the number two pencil taken out of my

fastest lateralis than attending any day exactly you've had it done you're familiar um but yeah that's exactly what happened now so they they took this you know pencil-sized needle shoving in the vast lateralis exactly muscle we looked at. So the thigh muscle essentially, and took about the, he took biopsies before exercise, then them had had them do a resistance exercise bow. So it's like a 45 minute kind of standard, nothing crazy. You know, these were relatively untrained people, but they are Swedish. So they're probably fitter than Americans and, but had them, you know, do a resistance exercise bout. And then he took biopsies 30 minutes after the resistance exercise bout, three hours, eight hours, and then 24 hours. So the thought being that we could, or he could look at sort of the, the mainly the ribosome biogenesis response to, to a bout of

exercise to kind of get a sense for how dynamic this process is. And then also there was another group that was an endurance group where they did the same thing. We didn't publish on, we did publish on that, but not in the study we're about to talk about. But also there was a group where we just took the biopsy only as well. And so he had the people come in, different set of people come in,

just took biopsies throughout that time course without the exercise, because the biopsies themselves can cause things to happen, but also circadian rhythm and diet and all these things are interacting to cause these changes in gene expression because the biopsies themselves can cause things to happen, but also circadian rhythm and diet and all these things are interacting to cause these changes in gene expression that we looked at. So in any case, so that study was done a while ago and he had that tissue. And the first study we published on this was in 20, I want to say it was 2021, where again, we wanted to just look at

the ribosome biogenesis response. So how do ribosomes get made after exercise and what's controlling it? Because we think that this could be really important for muscle growth. Again, the ribosomes are the construction workers of the cells. They're the things that take the messenger RNAs and turn them into proteins, and then those can go off in the cell and do whatever they're going to do. And so that was the first paper we published back in 2021. And we did this time course where we showed, you know, how this ribosome biogenesis response occurs after exercise and the different things that are regulating it. We found some evidence that there are some epigenetic sort of things that may control this process as well as genetic

things that may control this process and may lead to susceptibility to hypertrophy across different people. So that was really cool. That was the first study. But we still had tissue and that may control this process and may lead to susceptibility to hypertrophy across different people. So that was really cool. That was the first study. But we still had tissue and we wanted to do more. And so in a follow-up study, which is this paper that you referred to, this preprint that's up online now, we basically wanted to look at all of the genes that were being expressed at every one of those time points after exercise relative to pre and try to understand what are the things at the molecular level that are potentially the most influential for driving muscle hypertrophy, right? Because, you know,

as you guys know, after you exercise, all these different molecular things start to happen in the muscle. And once you do this, you know, time and time again, those molecular things kind of build on each other and ultimately lead to adaptation, right? So our thought was if we could kind of understand what's going on in that first 24 hours after exercise on the molecular level, it could point us in the direction of things that are the most influential factors that could drive muscle growth. Shark family, I want to take a quick break. If you are enjoying today's conversation, I want to invite you to come over to rapidhealthreport.com. When you get to rapidhealthreport.com, you will see an area for you to opt in, in which you can see Dan Garner read through my lab work. Now, you know that we've been working at Rapid Health Optimization on programs for optimizing health. Now, what does that actually mean? It means in three parts, we're going to be doing a ton of deep dive into your labs. That means the inside

out approach. So we're not going to be guessing your macros. We're not going to be guessing the total calories that you need. We're actually going to be doing all the work to uncover everything that you have going on inside you. Nutrition, supplementation, sleep. And then we're going to go through and analyze your lifestyle. Dr. Andy Galpin is going to build out a lifestyle protocol based on the severity of your concerns, and then we're going to also build out all the programs that go into that based on the most severe things first. This truly is a world-class program, and we invite you to see step one of this process by going over to rapidhealthreport.com. You can see Dan reading my labs, the nutrition and supplementation that he has recommended that

has radically shifted the way that I sleep, the energy that I have during the day, my total testosterone level, and just my ability to trust and have confidence in my health going forward. I really, really hope that you're able to go over to rapidealthreport.com, watch the video of my labs and see what is possible. And if it is something that you are interested in, please schedule a call with me on that page. Once again, it's rapidealthreport.com and let's get back to the show. It could point us in the direction of things that are the most influential factors that could drive muscle growth. So that was kind of the goal of this paper was to profile the transcriptome,

what we'll call it. So all of the messenger RNAs that are being made at each one of those time points after exercise. And then we coupled that with some epigenetic measures where we're looking at what could be controlling the expression of those genes. So epigenetics is essentially the study of what can control the expression of genes that doesn't have to do with changing the genetic code itself. So we're talking about how genes get accessed. So we looked at some factors related to that. We did a whole lot of bioinformatics and molecular biology to kind of point us towards what are the things that are really controlling this molecular response after a bout of exercise, specifically about a resistance exercise. We're interested in muscle growth.

And so we did all this analysis and we came up with this factor that was called MYC, which is actually an oncogene. And so an oncogene is a gene that when it gets dysregulated causes cancer. So there's a lot of genes that if they go wrong and they start getting expressed when they're not supposed to, or where they're not supposed to, they cause tumors. It's not a good, it's not a good thing always, but here's the thing about tumors. Can I, can I pause for a second? Just so I'm following along in the right. When we get into this into this uh what you're talking about is having or when you go and lift weights um it is going to create a signal to express specific genes which will allow for muscle adaptation due to the correct thing yep bang on that's right give me a PhD, Doug Larson. Let's go,

buddy. I just want to make sure that I'm speaking human to the, uh, and understanding this. That's what I'm going to say things. And then you're going to do it. Doug's giving me all the degrees right now. So we're good. So, yeah, I mean, all of in every single cell in our body has our DNA template, every cell has it, right. And that's how, you know, cells become what they are. So like we have the DNA, every cell in our body has the DNA template to become an eye cell, to become a hair cell, become a brain cell, a muscle cell, whatever. And what happens is that as we develop, you know, through embryogenesis, and as we go through development and become human beings, all these different cells start to specialize. And so, yeah, we still have all

genes that code for my muscle to become an eye cell if it wanted to, but we get so far down the developmental path that it's no longer going to become that anymore. But stem cells can maintain the ability to become these different things, which is really cool. And our muscle has stem cells, so it can become different things. But, but like a muscle fiber, for instance, it's, it's basically committed to being a muscle at that point. It's so far along in this developmental trajectory. And what kind of directs that is epigenetics in a lot of ways. So basically what's happening is we have all the genes, let's say 20,000 of them. And through epigenetics, we shut down like half of those. Right. And so just turn on the genes that are necessary for muscle to be muscle. Um, we don't want like eye genes and tooth genes and long genes getting turned on in our muscles, right? Some of those, and there's shared pathways between all the

different tissues. And so like, you know, I don't want to make it seem like all genes get turned off and then only very small subsets get turned on a lot. There's a lot of shared pathways, but there's a lot of genes that are specific to a certain tissue that only need to be turned on in that tissue to maintain its identity. And so, yeah, so all these genes get turned on and turned off and repressed to basically make a tissue what it is. So in muscle, for instance, you're going to have a lot of contractile myosins. get turned on and turned off and repressed to basically make a tissue what it is. So in muscle, for instance, you're going to have a lot of contractile myosins.

You're going to have Titan. You're going to have all these different things that are myosin heavy chains, right? That are specific to muscle being muscle. But the thing is, this is a very dynamic process, right? When you exercise, when you go to the gym, you lift a weight, you know, a couple of times, these gene programs get turned on. You might not turn on, you know, the eye genes because those have already been epigenetically repressed, but you may turn on other genes that are more accessible that are going to lead to the adaptive response. So, you know, you go lift your weight and maybe a gene

related to muscle growth has an epigenetic change that allows it to become expressed. And then that gene starts getting expressed and then ribosomes grab that gene, turn it into a protein. And that protein goes off and does whatever it was supposed to do. Maybe it's a myosin gene. So it gets turned into myosin and then it helps with contract it with contraction. So that in very broad strokes is like molecular biology. right and so uh so yeah so since i consolidated dug into like a one sentence we should be good i understand now for for you know the audience that maybe is not familiar with us that's perfect because that's exactly really what you need to know to understand the conversation so um but you know diving in a little deeper that that's kind of in broad strokes

which is that's like the central dogma molecular biology for all intents and purposes. Um, and so wait, so here's this pause. So zooming out from that, like what are the most practical takeaways for people that, that they already lift weights, they already are taking pretty good care of themselves. They already train hard, et cetera. Like from, from what you have learned from doing all of your various research, like what are like the little nuances or, or adjustments someone can make for their training to further express XYZ gene or build more muscle, et cetera? Yeah, that's a, that's a great question. I mean, cause truth is, I mean, I think a lot of maybe what directs somebody's susceptibility to growth, for instance, for muscle hypertrophy, there's definitely a genetic

component there that you don't really have a huge amount of control over. And back to the study that we talked about earlier, the first study we did was we were looking at, so basically, most genes in your body have two copies, right? You have one from your mom and one from your dad. There are other genes that are not that way, though. There are some genes like your ribosomal genes, the genes that code for the ribosomes that You may have 50, someone else may have 150. And so that right there could be a difference maker as far as your ability to put on muscle mass. Because if you have an enhanced ability to make more ribosomes because you have more copies of the gene

than the person beside you or your brother or your sister or whatever, it may predispose you to being a little more susceptible to growing muscle in response to resistance exercise. And so I know I'm getting off track a little bit here. And actually there's a paper now that's in bioarchive that suggests maybe that's not the case because we showed some evidence that it could be, but now someone else is saying, Oh, maybe not. We don't know. And so I, but again, there's these genetic aspects that are definitely directing, you know, people's susceptibility to, um, to, uh, adapt to resistance training, for instance. So there may at some point be precedent

for, you know, doing genetic testing for certain things like that to see, oh, you know, this person may, if we can prove that that is something that would lead to, uh, better hypertrophic responses, for instance, or greater, There may be, you know, certain gene markers we can look at with genetic testing and say, oh, this person, you know, could be predisposed to maybe putting on more muscle mass. So let's, you know, maybe direct them more towards strength exercise or something like that. But it's not really your question. Yeah, I would imagine almost as people are kids, like immediately, you could probably, when do you feel like you would be able to see where

the kind of like on the scale of, to your past example, like, eh, you don't really have the hypertrophy, uh, signature, so to say, to go along with it. And then all of a sudden it's like Phil Heath shows up and you're like, Oh, that guy's going to win all the Olympias. You know he can build muscle. Yeah. And I mean, I feel like that stuff sort of susses itself out naturally sometimes because people gravitate towards what they're good at. And maybe the first time they lift a weight, they got a good response. Well, I think about it with like a Ryan Grimsland where it's like,

that guy looked, if you just saw him in a grocery store, you'd be like, yeah, that guy's in good shape. And then you watch him lift weights and you go, oh, like that. looked if you just saw him in a grocery store you'd be like yeah that guy's in good shape and then you watch him lift weights you go oh like that that's wild you snatch 315 or whatever 345 like and you weigh 160 pounds interesting yeah yeah it's and i don't want finding those people oh yeah as far as finding those people i mean yeah we might get you know and so to the future in some dystopian society where he gets this genetic and we're like, oh, we've identified these are the genes that are associated with hypertrophy and you have a lot of ribosomal genes and blah, blah, blah. I'm using that as an example because we really don't know whether or not that's a cause for growth. Right. But, um, I think your original question

was how would I tweak my training to get these little molecular results? Then the truth is, I don't know. Basically what I study, and this is probably like, you know, much to your guys' chagrin as far as the power gas goes, but much of what I study is post whatever it is you just did. So post lifting a weight, whatever way you lifted it and looking at what happens downstream to maybe facilitate this hypertrophic process. And what I can say, at least with what I've been studying with this, this Mick gene that I'm interested in, I'll tell you guys a little more about there has been evidence in literature to suggest that people that have an exaggerated response of this gene response to resistance exercise, um, they tend to put on more muscle mass. But again, that's just a relationship

in a small study, and it doesn't really prove anything. It's kind of an interesting little piece of information, and it had never been shown, well, at least prior to our study, that if you manipulate this gene, that it can cause growth. And so that's really like trying to get at the very like basic level of information is if we manipulate this thing, does it cause a result that we would expect or cause a result that's related to muscle growth? And that's really, and to like zoom all the way out, like in order to answer that question, you have to understand basically, or yeah, at least have an idea of everything that's going on in the muscle during recovery, right? Like, and there's so many things, right? Like we're talking about, you know,

an epigenetic chain, epigenetic changes across the whole genome that leads to genes that ultimately become expressed, which leads to proteins that ultimately get made, which maybe need to then become phosphorylated and activated to go and have their effect. And then they need to go localize the correct area. And then there needs to be enough of them in order to actually accumulate and cause growth. I mean, it's a very exquisite interplay of things that are happening at several different levels.

And we're just zooming in on one aspect of this. What are the genes that are being expressed after you go and lift a weight? And then of those genes, which of these do we think is the most influential? And then if we can go manipulate that gene and cause it, and does it cause growth or increase in strength if we go and manipulate that specific gene?

So basically we're taking this like really big 30,000 foot view. Let's just look at everything. And then we're gonna drill down, drill down, drill down, drill down to what we think is most important. And then we're going to test that. And I'll tell you, it takes a long, I mean, it takes a long time. We started this project five or six years ago. Right. And it's taken that long to finally get to a place where it's like, okay, we think we might have something here. We've done the experiments where we think

we have something. And so we're going to put that out there and see, you know, what people think. So, yeah, I mean, it's, it's a very long process. Yeah, you know, to what degree our pharmaceutical companies like trying to look at this type of research to to develop drugs that epigenetically express some genes over others, or, you know, you mentioned ribosomes earlier, like, if you have a drug that, say, increases the amount of ribosomes you have by 25%, now you can put on more muscle mass. If that was really a thing, I don't know if that example works out perfectly, but you know, our, our pharmaceutical companies trying to do things like this to, to get an edge on a, on a new drug that helps performance. I would say they probably are. And if they're, the companies are doing that are probably not

advertising it. Cause it's probably going to result in something a list that somebody will use for performance. But it's a perfect question, though, for a couple reasons. The first is a lot of times people try to repurpose drugs that already exist, right? Because a lot of times drugs have a main target, but they have a lot of ancillary targets, right? Other targets that can have off target effects that may or may or may not be anticipated i mean look at what is it viagra right that was never designed to be a what it is you know that was like an off target they're like oh that's interesting and so you know someone increase that blood a little bit well didn't they didn't they actually find that out by like the, I don't know the exact specifics here,

but like they did a study, they gave all the drugs out to everybody. And then at the end of the study, they needed to like recollect all the leftover pills and like nobody turned them in. Everyone kept them. And they were like, how come nobody, how come nobody will give these back? And then they found out like, oh, there's this added benefit that we didn't know about. Exactly. They were testing it for blood pressure or something else at the time. Exactly. And so, but I think that's a little bit of like a snapshot of like, perhaps the bigger pharmaceutical company where it's like, or bigger firms who companies that are like looking to repurpose things that already exist. Cause I mean, truth is, is very,

I'm not in this world, but I talked to people that are in like, it is super expensive, time-consuming, difficult to get a new drug to market. Right super expensive, time consuming, difficult to get a new drug to market. Right. And it's a lot easier to take a drug that already exists and look at some of the side effects and be like, well, that side effect actually could be beneficial for this particular instance or this particular, you know, occasion where we're trying to leverage this aspect of biology. And so I think probably what, well, I work in aging a good bit, like, you know, skeletal muscle aging, as we know, muscles get smaller as we age, and we're trying to prevent that exercise is the best drug. But there are other drugs, right?

There's, you know, people get really into trying to biohack with different drugs, like metformin being one of them, rapamycin, like there's a lot of like, quote unquote, anti-aging drugs. And some of them, they're not really geared towards muscle hypertrophy per se, right? But what's happening now is people are starting to see, okay, well, if we take rapamycin or metformin or whatever, and then we go exercise, it can be counterintuitive, counterproductive, actually. So you're better off perhaps maybe just exercising as opposed to doing exercise and the drug. I mean, if you don't want to exercise and maybe you're a little unhealthy,

maybe taking those drugs can have anti-aging effects. But when you combine it with exercise, it isn't, those things aren't always synergistic or they don't always play well together. Which is, I think, something we're starting to figure out a little bit more. But I think if I had to guess, people were trying to look at some of these studies with these big omics data sets and trying to find drugs that could potentially target some of these things. And what I'm interested in, and I alluded to it a little bit before, MYC is an oncogene. It's also something called a Yamanaka factor, which basically, if you take a cell that is, let's just say a skin cell, right? Like take

it right off your body, a skin fibroblast, and we put it in a dish. It's a skin cell. It knows what it is. It's not going to be anything other than a skin cell. It's already gone through its developmental trajectory. It's skin. And so what you can do though, and that somebody, a guy named Shinya Yamanaka and Sir John B. Gurdon won a Nobel prize for this. They figured out that if you overexpress these four genes, which wouldn't normally be expressed in the skin cell, those have been shut down epigenetically. But if you cause those to get re-expressed, that skin cell can then become what's called an induced pluripotent stem cell, which you can then direct to become anything else you want it to. It can become muscle. It can become whatever. Yeah. I sell. And so these are

these Yamanaka factors. And this is something that people are really interested in. It's like, oh, can we think of drugs that would target these Yamanaka factors? And, you know, maybe there's would be some benefit there because it's been shown that when you induce these Yamanaka factors by basically wiping the epigenetic slate kind of clean, the cell goes back to a younger state. It goes back to a stem cell state, which is the state it was before it became a differentiated cell. So you're essentially like kind of turning back time in some ways. And people have really latched onto this idea.

And people are looking for drugs that try to leverage this kind of altering of the epigenetic landscape of cells to get them to become younger. And a lot of it has to do with these Yamanaka factors. MYC is one of them. But as I said before, if you overexpress Mick and you manipulate it in a way that it wasn't meant to be manipulated, it causes cancer. And we know that if you overexpress these Yamanaka factors for too long in a living organism or in a cell, it turns into a tumor. They turn into teratomas, you know, like, so that's not good. So there is a druggable opportunity here,

but at the same time, it needs to be done in such a careful way. And it needs to be timed so perfectly that if you just turn it on for a little too long, you're going to get a bad result. And so that it's like, we have a template for what we can do to manipulate cells, to get them to do what we want to do. But it's a matter of like, how do we deliver it to where we want it to be delivered? How do we turn it on for the right amount of time and the right dosage to get the effect we want without getting terrible side effects. And so people are starting to try to find drugs that are mimicking aspects of turning on these genes, but don't actually turn on the genes, you know, because if you turn them off in the

wrong way, you get cancer. And so, um, so going full circle back now to muscle where we did this big profiling of all the muscles that get turned on after you lift a weight. Right. And so now we know at 30 minutes, these genes turn on at three hours, these genes turn on at eight hours, these genes turn on. And then at 24, these genes are still turned on. And so like, we have this like kind of roadmap of all the genes that get turned on after exercise. Super cool. Right. We did all this analysis and we kind of drilled it down to Mick. We did a lot of things that kind of told us, we think Mick's really important, but I just told you that turning on Mick can be a bad thing. Right. Well, here's the thing with anything. There's like this,

this like Goldilocks zone, right. Where like, you can turn something on for a period of time, but then it needs to come back down to baseline in order to get the effect you want. Cause if you just leave it on bad things happen. So that's pretty much what we found is that Mick after exercise in the muscle, it goes up, it peaks, and then it starts to come back down. It's getting back towards baseline levels at 24 hours. And so you just kind of have this nice curve. So every time you go to the gym, the gene gets turned on all the things that affects get turned on, on proteins get made, then it goes back to baseline. And this is, you know, the same thing that happens with like mTOR, right? I'm sure you guys are familiar with what mTOR is. It's the same

thing. Like you go to the gym, mTOR becomes activated, but it doesn't stay activated forever. It eventually goes back to it's like basal level. If you turn it on too much, the muscle basically develops a myopathy, you know, like it's a very powerful thing. These growth signals, very, very powerful. You turn them on for too long, you get bad results. You have to control how much it comes on and when it gets turned off

in order to kind of understand what it's really doing. And that's exactly what we did. All of our human data pointed us towards this oncogene, this really powerful gene that controls all these other genes that get turned on after exercise. So then we just were like, okay, well, how do we control this, right? How do we test whether this is important for muscle growth? So what we did is we went and we made a mouse model. So this is where, you know, the power of the mouse model sort of comes into play. Like, you know, mouse mice aren't people, right? We all know this. Everybody's clearly, but they do have muscles that

adapt to exercise and have similar fiber types and all these different things. So they can be used as a surrogate. And so our human data said, you should probably look at this gene. So we made a mouse where we can literally turn on this gene at any point in the lifespan of the mouse and then turn it off as well. So we can control when it goes up and when it goes down only in the muscle fibers. So that's what we did. We made a mouse model and we turned on the gene for four weeks. We just turned it on for two days at a time, two days on five days on two days on five days off. We turned the gene on, turn the gene off, basically trying to mimic more or less an acute exercise response. Right.

And so that's what we did. And when we did that, we found that in the soleus muscle, which is the muscle that's from a fiber type perspective, most similar to like the VL in a, in a human being, which is the muscle we grabbed samples from, for the study, we found that it grew. We grew from a whole muscle perspective and it grew in the different fiber types. And so this is telling us that, you know, we did this big kind of survey of all the genes. We whittled it down.

We developed a mouse model. And then we showed, hey, when we control this gene in the right way, bad things happen or good things happen. But if we leave it uncontrolled, bad things happen. And incidentally, as soon as we put up our pre paper, which is now in review, another group, like a week before, put up another paper and they just turned it on and left it on. So they took a similar approach, but just said, Hey, we're just going to turn this oncogene on and just leave it on for like a week. And what happens? Myopathy. Yeah. Muscle atrophies, bad things happen. And so that's

what we would have hypothesized. And so that's, um, it just kind of goes to show though, that we're kind of entering, I think this new way of viewing how molecular aspects are controlling recovery. And it really is that, that recovery component, right? Like you're not, you're, you lift the weight and then you stop lifting the weight and then all the things happen. And then it goes back to baseline. Then you go lift the weight and to get that cascade to happen again. And it's like, you can't always be lifting the weight. Yeah. Two questions that come up. Does intensity play a factor in how long this is around? I'll come back to the second one since you shook your head.

I would suspect probably yes. I would. The thing is I'm trying to, I'm'll come back to the second one since you shook your head. Yeah, I would suspect probably yes. The thing is, I'm trying to think from the literature what I know and what I can say confidently because truth is we're still at the place where it's like, does this even have an effect? And if it does, then how do we dose it, right? And so my knee-j jerk reaction is yes. And the reason why I say that is because we originally worked, we published a series of papers prior to the one I'm talking about. And when we did that, we used a mouse model again, where we basically surgically caused the mouse to be lifting the weight like constantly, like every time it step, it was like it was lifting away.

And so it was like a constant resistance stimulus. And when we do that, this gene goes through the roof and we see like remarkable growth, like in a matter of two weeks, the muscle will double in size. And so that leads me to think that, yeah, there's probably some dose response happening here. Like if you lift more intensely, maybe you get a more robust response and maybe that could lead to more growth. On that same token though, as you train more, a lot of times the things that go up a lot when you're not trained, like the molecular things that increase when you're not well-trained tend to become a little more blunted, the more trained you become. And then you have to like goose it a little bit more with like more training volume, more intensity to get that same response.

Right. But I think also what we're beginning to discover in the muscle molecular biology sort of field is that perhaps there's a timing component here. Maybe it's not that it doesn't go up anymore, but when it used to peak, let's say at eight hours after you exercise, it's now peaking at two. So you have this like more rapid response and maybe we've just been missing it. But then the question becomes, how can we get it to be rapid and perhaps a little bit more sustained to get, to get a more like robust hypertrophy response. And that's, I think an area where the field is sort of going, but to answer your question somewhat indirectly,

I do think there's probably an intensity component to it. I just don't know the answer right now. Yeah, I feel like there would almost have to be to elicit some sort of response in the cell. Like me going and just like picking up my kids is not, there's no need for recovery. An actual real training session, your body has to click some sort of mechanism into place to go. That was a lot. We need to repair. And this is the process. That was more than just lifting up my kid. Yeah. Like exactly. For sure. Um, we would all be, we'd all have tumors everywhere. If like just normal daily actions, this is like giant response to like, uh, just, I don't know why all these tumors are growing. It's like, well, each step, each step is a problem. Sit still.

Well, I mean, exercise ideally does the opposite of that, right? Definitely hope that's not the case. So, um, and then I was also super curious, um, talking to us here on this show, it's very obvious that, uh, we want people lifting weights. We understand the, the health benefits of lifting weights. But Doug bringing up kind of like the pharmaceutical companies, have you seen, or do you believe that in the future we might see a way, you mentioned cancer, tumors, things like that, that we can actually go in and like time this response, whether that's pharmacology, which would be unfortunate instead of just people like lifting weights, but really be able to kind of like put some sort of method in place that there there's a way that you can control this response in the same way that you guys did with the mice

so that we aren't accidentally or like unknowingly creating this like tumor growth. Right. And I think that's ultimately where everybody wants to go because, well, first of all, from a performance perspective, right? Like everybody wants to be more jacked. I would like to be more jacked. I wish I could figure that out so I could be fitter. But I mean, right. It's not Viagra. But yeah, I think that's where and the thing is, from a clinical perspective, too, is a lot of people that can exercise, right, or have a severely inhibited ability to do it, or people that have to are sick, they're laying in bed, or even when you get old, you lose muscle mass, your adaptability declines. So there's many instances for why having a pill isn't a bad thing, you know, but obviously exercise or response to exercise is so multifactorial and there's this timing component of when things are happening.

And I mean, it is a pie in the sky idea, but it exercises is doing so many things, but let's, let's just pare it down and just say, okay, maybe we can find a pill that activates MYC only in the muscle for a very short period of time to help amplify the exercise response or mimic the exercise response even. Then the hurdle becomes, if we could figure that out and have no other side effects, the hurdle becomes how do we deliver it only to muscle, right? Because you grab a pill down, a lot of times it's not targeted to anything. It's just going to go everywhere and it'll, you know, latch

onto the receptors and the cells that you need it to, but it'll, you know, go other places too. And in this particular instance, when we're talking about an oncogene, something we know causes cancer when it's dysregulated, the risk of that is very, very high. And so, um, and then like, let's say it gets into your heart and then it has negative, because heart's a striated muscle too, and it's contracting. And so, um, there's a lot of, a lot of science I would need to have. My brain just went crazy when you mentioned the heart. So is this specific to the muscle group that is being activated in a workout? Or is this more of a like whole body systemic way? Because I would imagine if we're lifting weights quickly and our heart starts beating faster, it would have the same result, but you wouldn't want your heart to

just be in a hypertrophy growth at all. That would be very bad. That would be well, other studies before long before mine have looked at a lot of times what happens in the skeletal muscle research is that the cardiac people do it first. And so cardiac folks latched onto this Mick thing too, and they overexpressed it. And yeah, the heart got huge, like the heart totally bonded to it. But not necessarily in a good way, because hypertrophic cardiomyopathy is not good. Like, yeah, a little muscle hypertrophy is. And so, yeah, I mean, it's very possible that if there was an off target effect off the heart, that would be bad news bears, you know. And so that's why again, the specificity of, of trying to overexpress

something or, or induce something or just manipulate and control something is so, so important. And like, you know, we've known for a long time that when you knock down myostatin, you know, which is, you know, it's a negative regulator of muscle growth. So if you ever have seen those, those cows, those Belgian blue cows that are like yoked out of the mind or those whippet dogs, yeah, those cows, things that are probably yoked out of the mind or those whippet dogs. Yeah, those cows. The thing is that they're probably not delicious. They have no fat. And so people thought that was going to be the thing, like those myostatin inhibitors, like that was supposed to be the next wave of muscle growth. And it didn't really play out. Well, yeah, we still I mean, it's still in clinical trials, people still study it. And

it's a very, I mean, it's taught us so much about the regulation of muscle mass with that one discovery. I mean, you know, muscle biologists typically don't win Nobel prizes, but like, you know, that was like a turning point in the muscle biology fields. Like, wow, this negative regulator, look what it does. You just knock this one thing out. Look what it does. It makes a cow look like Phil Heath, you know, like insanity.

But yeah, it's well worth googling for the audience if they've ever done this every time i cow and that and the greyhound or whatever that dog is yeah the whippets and even the mice that's right you knock it out in mice and the mice are just yoked out of their mind it's crazy every time i see one of those cows i'm like man i would love to have one of those things like people would know that we meant business. If they walk by our house, like, dude, look at your cow. What is going on? Distriations going across its arm. They look fake.

If you, if you don't know that they're real. Yeah. You think that it was Photoshop, but like in the original, one of the original papers, the Belgian blue cow, they show a picture in there,

in the article, the research article in the journal. And it's, papers, the Belgian blue cow, they show a picture in there, in the article, the research article in the journal. And it's, yeah, you're like, what is this? This is like before the times of Photoshop. So it's like, it's, that's real, man. Like it's great. And this is just a genetic, um, you know, uh, genetic problem with these, these cows, they don't have this negative regulator. So they grow out of control.

And so specifically in the muscle. And so it's, it's a while, but control. And so specifically in the muscle. And so it's a while, but also again, it speaks to the point. It's like, we know what happens when we knock this out, but it still hasn't really been leveraged into like this amazing drug that solves all muscle atrophy problems and stuff like that. And it's probably has something to do with the fact that there's a bunch of off target effects when you manipulate this thing too. And how do we control for that? And very, very difficult. And I mean, delivery mechanisms are a huge focus now, you know, like of trying to get things specifically to where we want them and only where we want them.

And it's still a challenge. I mean, that's a major challenge in the cancer field. If we could figure out how to deliver stuff only to tumors, there's a lot of stuff we could put in a tumor that would do it. And so like, you know, this is going to be an ongoing problem and, and for muscle it's getting better. Um, there's a lot of different delivery mechanisms that can be used that target skeletal muscle specifically, but, um, still you got to think about the heart. You got to think about a lot of, and then you have to think about how often, if you just put something in there, it's just going to get expressed all the time and cause a problem. Like there are so many hurdles still, we're still kind of in the phase of discovery, I think. Yeah. Kind of as a follow on, like the second question I wanted to ask, um, kind of after the intensity

side was, um, kind of as we, as we wrap here, um, what, or how have you guys looked at like a, a post workout nutrition, um, different and, and kind of how much that changes on the efficiency of this process? Yeah, no, I mean, that's, I've done basically no research with nutrition, being perfectly honest with you. And I feel like the answer is yes. I mean, a lot of other people, a lot of people have looked at when you take, you know, certain proteins and different things, those proteins, how this molecular response changes or how the protein synthesis response changes and all these things. There's a rich literature on that.

It's not really my area. Specifically though, with what I'm talking about, Mick, I actually don't know. I would assume somebody has done resistance exercise with people, given them different supplements and looked at response as part of other things. I don't know off the top of my head. Yeah. My, my uneducated guess, uh, kind of would go to like something that is much easier to digest, like a whey protein shake or something like that, where it's just, it's, it, you digest almost all of it. It's very easy to get through, um, to the muscles. And then the idea of like going and eating like a steak or something that just takes like three days to digest. And like, you're just, it just probably wouldn't have the

same speed, um, if it even matters at all. But, um, this was fantastic, man. We got to have you back on and, uh, dive into this again. I, uh, I'd love if you could tell the people kind of where, where they can learn more about your research, um, in your lab. Yeah. Yeah. So, I mean, uh, you know, I'm on the, I'm on the Twitter and, uh, and the Instagram and I was popular as a Zandy and some of these other folks, but I do have it and get on from time to time. Of course I have a lab website. Uh, you can just Google my name, Kevin M U R A C H and I'll come up and I have a lab website. You can check it out. Um, and then, you know, on there, there's my email if you want to contact me directly. So, um, yeah, there's a lot of resources out there and, uh and yeah, feel free to reach out if anybody has questions.

Beautiful. On the funding side for your lab, is there public funding areas for that? Yeah. I'm funded by the National Institutes of Health. I have a couple of grants through them and I have some funding for the American Federation for aging research. Is that where you're asking? Like where am I for like donations? Oh, for donations. Yeah. I've never thought about that.

I would love some donations. If somebody wants to. Galpin has something set up. I bet he does. Just Venmo Galpin. It's like, yeah, Venmo Andy and he'll send it on to me.

Yeah. Keep passing it through Venmo. See what happens. No, actually, I should think more about that that thought has never crossed my mind because i just write all day so there you go i love it fantastic man awesome doug larson yeah genius people could just send me money uh we're right on kevin appreciate you coming on the show. Always cool to hear the current state of muscle physiology.

So appreciate you being here. Enjoyed it. Thanks for the great questions. And it was a pleasure to talk to you guys. Take care. For sure. I'm on Instagram, Douglas C. Larson. And I am Anders Barner at Anders Barner.

We are barbell shrug to barbell underscore shrug. Make sure you get over to rapidhealthreport.com. That is where Dan Garner and Dr. Andy Galpin are doing a free lab lifestyle and performance analysis that you can access for free at rapidhealthreport.com. Friends, we will see you guys next week.