#80 - Epigenetics of exercise adaptation and "muscle memory" with Dr Kevin Murach

hello and welcome to inside exercise I'm ameritus Professor Glen McConnell from Victoria University in Australia the idea behind inside exercise is to bring to you the absolute who's who of exercise research so exercise physiology exercise metabolism and exercise and health and what I'm really wanting is for you to get your exercise information from the research experts rather than from influencers and indeed today I bring to you assistant professor Kevin marak from the University of Arkansas in the USA Kevin is a rising star in muscle research so he looks at muscle mass what regulates muscle mass

how resistance training increases muscle mass and also we talked today about muscle memory so the fact that if you do exercise training and then you have a period of time where you don't exercise and then you exercise again it appears that the muscle responds quicker the second time so there's been some sort of muscle memory so we talk about what is the evidence for muscle memory and how is it regulated so at the muscle level is it genetics is it epigenetics is it changes within the muscle gene expression Etc I found them really fun guy

to chat with he's really on top of his field I learned a lot I think you will too so stick around if you'd like to do me a favor and also help spread the word about inside exercise please like comment subscribe Etc because then it makes it more likely if someone does a search about exercise that the algorithm will suggest inside exercise now with all the podcasts it's much better if you watch the whole podcast to get the full context but if you'd like to jump around a little bit um for example if we're talking

about mechanisms and you'd rather skip over that then you can look down at the at the not and you can see the time stamps are there so it shows at each time what we're talking about so you can skip around a little bit okay so enjoy the chat hi Kevin how you doing welcome to inside exercise thanks for coming on thanks for having me I'm very excited I appreciate the invite oh no yeah I'm I'm really happy to have you on you're you're the F the second official sort of rising star you've got an amazing

track record for how long you've been around we'll talk about that so the first one was the the great Carlos oin from uh University of Copenhagen who I met a couple times I was out there so it was great so people can look that up but um yeah so we're going to talk about um epigenetics so we'll explain what that is and and muscle memory and things like that um but like I what I like to do at the start is just sort of talk about how did you actually get in to exercise research to

start with yeah I mean I was uh like many other people on this podcast was an athlete not I I personally wasn't a very talented one but uh I played Sports in colle or in high school not in college wasn't even that good I played Sports in high school um tennis soccer and I got into weightlifting um then went off to college and you know continued kind of just uh exercising for the sake of exercising I enjoyed it I I specifically enjoyed lifting weight so I kind of all my research reflects back on that like

I view everything through the lens of like you know weightlifting um so uh yeah but I really enjoyed that aspect of um of exercising and so in college you know started lifting weights more in started thinking more about you know how do my muscles grow like how does this process happen um just kind of became more of a personal interest but it around that time I realized I could study exercise science as like a profession or as a major at that time but I didn't realize I could become a profession so I be you know

studied exercise science at UNCC uh Chapel Hill in North Carolina and then uh you know once I got that degree I didn't really you know know what to do with it and so I decided to get a master's exercise phys ology and that was at James Madison University I worked with a guy named Nick luden who had just graduated with his PhD from Ball State University and so he T James Madison he said you know you should go to Ball State that's where I went I think You' like it so I uh you know went

and got my PhD at Ball State University and you know at this point I had you know started doing some different types of exercise started riding the bike a little more um you know road bike things like that um so I you know was I guess training concurrently so to say but um so yeah but again this interest in personal interest and exercise sort of evolved into more of an academic interest at this point doing as you know muscle biopsy work and single muscle fiber physiology fiber typing things like that and then after after I

graduated from the hpl at ballate I went and did a sixe postto with uh Dr Charlotte Peterson and Dr John McCarthy um so did a lot of more pre-clinical work you know looking with mice doing a lot of cells uh genetically modified Mouse models really focused on muscle stem cells satellite cells uh primarily and it was around that time I started kind of thinking more about epigenetics and aging in in skeletal muscle um with exercise as well so I started transitioning towards the end of that time into those areas which is what I study now

in my uh my own laboratory at University of Arkansas so that's kind of like my uh my academic story arc but it began with a personal interest and just kind of evolved into I can study muscle adaptation for a living that's amazing so I just kind of kept down that yeah you've been doing amazingly well so I I don't know looking at Google Scholar looked like your first citations were sort of 2015 or something is that right um yeah that sounds great yeah ago when did you get your PhD uh I finished in 2015 yep

yeah so about that so that's amazing because you got an H I don't know people know what an H index is I've mentioned it here and there but an H index is um the number of times you've been SED per paper so if you have an H index of one you've got like one paper that's been cited once you might have three papers but you've had you know one citation one paper an H index of 20 is you've got like 20 papers have been cited 20 times or more you might have 40 papers you've got

an H index on Google Scholar anyway which is slightly more generous than than Webber science of 31 already and you said something like how many papers did you say you got during your post do you know I feel I it was between I want to say it was between 35 and 40 I don't know the exact number but it was in that range um I was we were very productive at the University of Kentucky and it was just me of course like it couldn't have been yeah I you know I think first author but a

lot there was a lot of collaboration going on and so very very rich environment for for productivity yeah so you're doing great so as I said second Rising I'd call officially a rising star and you said you just got a new investigator award uh what was that one yeah from the American physiological Society for like sell molecular physiology section so a couple of nice folks nominated me and yeah so that's uh that's cool so I'll be at that conference in uh what whenever it is when is that conference it's in April so I'm gonna go

to that okay okay great right so we're going to talk about um epigenetics and muscle memory so maybe we'll just talk a little bit about what epigenetics is uh in a little bit but if we just talk about this muscle memory concept so sort of gets you know banded around a little bit um I guess lay people sort of know it's almost like saying oh I'm you know running to the running to the bus my legs are burning it's a lactate you know it's like maybe maybe not you know but so so what is what

is muscle memory and when people talk about that and I guess it's a bit of a controversial term and yeah sure well I think it controversial Andor has multiple meanings to different people it's probably both of those things um yeah a lot of people think when they say muscle memory they take I think probably the most you know immediate example is like riding a bike they think you know oh it's muscle memory because that's how I know how to ride a bike even though I haven't ridden one in 20 years and um you know that's

one possible kind of explanation interpretation of what that means uh that probably more related to like you know um neuromuscular or or neural patterning things like that that's more probably in the brain and spinal cord when I think about muscle memory I'm thinking more in like the muscle cell so like in the muscle fibers themselves and basically changes long-term changes that could potentially be happening in the muscle in response to a stim Ulus that make it perhaps more adaptive in the future based on what it was exposed to so I think of it more as

like a a cellular phenomenon so to say and maybe not so much and it could there could be a neural component to it as well but I I study more the the cellular the muscle cellular component of what muscle memory is and I think like colloquially in the field and when we say the term muscle memory as muscle biologist we're saying like uh you know maybe you resistance train once upon time then you stop resistance training for whatever reason injury covid whatever happens you know and then you start training again that you're more sensitive to

that training and you adapt again to that training more quickly so you know what maybe took you eight weeks to gain muscle mass the first time maybe it only takes you four the next time and that's the the quote unquote muscle memory um so I think that's sort of the way that I think about it and that makes sense now um I guess I guess I start to think now I know you you've said you've done uh you know we tend to say preclinical so sort of you know my studies R studies Etc and I

know you've mainly done that I just wonder before we get into the nitty-gritty of what you've done because it's really interesting I think it sounds pretty convincing just wondering has that really been looked at people you know sort of looked at that very closely with humans just this concept of because as you say um it does feel like you know if you've done weight training before and you do it again it's like oh taking to this better than I did the first time but you sort of want wonder how much of that is just sort

of maybe confidence because you sort of know what you're doing and all that and and and like you said and I like the the fact you mentioned that like you know you get on a bike 20 years later and you still know how to do it that's not really the muscle it's sort of the the motor learning the sort of coordinating the and and even again it could be confidence right when you start to learn ride a bike you're you're totally scared right you got fall over your crashing your dirt on the grass the second

time you're more confident so I guess how much is that that has been sort of looked at in human you know yeah no there there has been some it's not like a rich literature at this point I would say but it's it is a a topic that is interesting to some muscle biologists and it has been studied in a couple different contexts in humans you know there was a a study early on by like uh Melena lyol that's her name yeah and uh CJ sunberg uh who's a Carol Ina where they did uh a study

where they like had people human beings come in and like endurance train and then looked at the dra trining response and saw if there was like you know change long-term changes in gene expression and whether that could lead to you know a more adaptive response to retraining in the endurance training kind of Realm but I think in the resistance training realm which is sort of where I reside um a guy named Adam Sharpes who is um university of a now he I don't know if he hasn't been on the podcast I don't think I no

he hasn't but his name's definitely been on the radar yeah yeah yeah yeah I would say reach out to him he'd be great um and so um but yeah he did a study in the year it must have been in 20 I want to say 15 17 in that range so not even that long ago where they did a study where they had people come in in resistance train they would take biopsies before and um and after the training then they drained them for a period of time and took biopsies and then retrained them and

took biopsies again it was a really involved study but they were probably one of the first ones in humans I believe the first ones in humans with the resistance train to show that yeah there is this sort of accelerated rebound response so if you had trained before and then you had gone back to your drained state after training so you had lost your hypertrophy um in your muscle strength that once you started training again it came back more quickly and they did show that using um some different some different methods of looking at muscle size

and since that time there's been a couple other studies uh in the end in the resistance training realm that have supported that too but it's not it's not like a massive body of literature at this point you know it's more kind of as you say like there was this anecdotal observation amongst people that go to the gym and then you know to start asking the question and doing real experiments to kind of tease it out a little more but there is evidence for it um it's just not a ton of it at at the moment

because they're hard studies to do right as you know like a a training study is hard to pull off and then you throw in draining and retraining those are tough stuff the same people hoping they don't drop out things like that yeah I guess I was thinking it sounds like it hasn't been done but I guess I was thinking because you're thinking mechanistic and I like that I always think mechanistic but I was just thinking if they you know looked at 10,000 people and ask them you know if you've done training and not you know

without the mechanisms and all that stuff sounds like no one's really done that um I wouldn't think so like a more epidemological study so to say even just yeah even just getting a bunch of people and just saying um just do you have your record so so so for example it's more with endurance training but you know straa you know yeah I don't okay so I'm more like a cyclist type guy so and I always get injured I've broken some many bones so I mainly ride indoors and I've got all the straa data and all

that and they've started actually going back and looking at straa data to see are you know people that I don't know ran 20 years ago are they better now or you know so you could actually do that I guess with endurance you could see if People's running times you know that that that had 10 years off and you know how quickly they got better and things like that I I guess I'm wondering about that but it's also I always think about endurance so we'll get to endurance later as well but yeah it it sounds it

sounds and and when you talk about your my St as well it sounds definitely that there's something going on there um so let's talk about that so so yeah why don't we just talk a bit without getting too mechanistic because I want to just sort of talk about and then we'll get into the the epigenetics and is it you know my Nuclear Junctions and and satellite sales and all that later if you just talk about what you've done in the mice and what you found and and also I guess I'll be of interest how long

that draining is um you know so in the shop the study you spoke about in humans and also in your mice studies yeah yeah uh so with the mice I I guess question or or hurdle number one with doing a mouse study with exercise is getting a mouse to exercise right of course like that's you have to have a model for that and um rats are a little bit more conducive to to training um in an I guess what I would call translatable Way um you know like an like maybe some sort of like weightlifting

or running wheel or something to that effect but uh my mice are a little trickier so our first challenge our first challenge yeah they don't like to learn things really there not a lot of operate condition going on with mice and so um so yeah so we ended up developing A new mouse model for exercise training and we called it Progressive weighted wheel running um Power for short and Corey Dungan one of my post colleagues was really the one that kind of first put the mice on the wheels and and and tested this out and

then we adopted it as a laboratory at Kentucky and it's but basically it's make a long story short we we put magnetic weights on the wheels in a very specific way so that they sort of have to resistance train while while running so it's voluntary for them but we found that when we trained mice this way you know we just gave them these wheels um with the special waiting that um they really took to it well and they they kind of became what I call athlete mice you know they we measured their heart function their

hearts got a lot bigger kind of an athletes heart um so say so like you know bigger left ventrical sort of thing and um and but also their muscles got a lot bigger um their Highland muscles specifically so that was the first thing so I was like okay now we have our training model um that's good so s i just to be interject on that so that's interesting yeah because when I first saw in your paper about this um sort of resisted uh running wheel it's it's pretty interesting because you don't normally think of that

so it's almost concurrent training here so they're doing when they're running it's hard so it's like cuz it's hard to imagine a human you'd have to run up a treadmill that so steep to actually get hypertrophy as well as you know endurance responses um and that is a a method that some people use is uphill high-intensity treadmill running um there are some groups that do that and um yeah that that is one way to do it um but we like our our real running it's voluntary it's not forced both have and disadvantages like you have

more control with the running and you know I think it's great I think it's a great model yeah the the voluntary wheel running is um yeah and the fact they do it they choose to do it as well and they do it enough to get actually you're saying cardiovascular responses so sort of endurance type responses and they get hypertophy yeah most certainly yeah they're muscles get bigger and their hearts get bigger and um yeah you know Mouse fiber types are an interesting conversation as far as like what they become oxidated these different things but yes

it seems like there's an there's a fiber type switch in a in a kind of a more slower Direction and um you know the type of things you'd expect to see if you if you train but yeah it is this kind of combination sort of concurrent approach where yeah sorry can I just interject can I ask um because I know I know people have done because I never forget seeing this picture in in a journal article where they got rats to do squats have you seen that where yeah exactly so they got them to sort

of stand up and they had this waight they got they had to was it they had to get down to eat and then they had to lift up or something and maybe maybe you can explain that a bit but I was wondering why um because you're interested mainly in strength why did you not go with um something that was more strength rather than concurrent I'm just wondering about that sure well at the time because when I was postto so this was you know between 2009 and 2015 so at that time there wasn't other than like

what we call synergist ablation which is a surgical model and um for studying muscle growth and that has advantages and disadvantages too but the there wasn't really uh uh anything out there the that was really other than like electrical stimulation of the muscle ofice we have to like anesthesized them and do all these things um so the the wheel running would it just made sense because we had running wheels and it was sort of it was a little bit of a um a convenience thing but at the same time it ended up working out better

than we would have expected but um but since that time there have been other models that have been developed that are more resistance kind of specific like uh there's one by Yan's group where they have like there's food up above them they have to push up grab the food and so but food is a reward yeah yours is voluntary no I like it I like it but I I guess I'm kind of ahead of so I'm just thinking ah if you did pure resistance training or pure weight training would you get the similar findings but

yeah just just keep going oh no it's a very valid question there is another model out there now that Troy hornberger developed that is very much more just resistance training but it's it's also very I guess I'll say labor intensive like you have to train each each Mouse like kind of you can train them simultaneously but you have to like it's like training people you have to have somebody there to do things whereas this is like they just get on the wheel they do their thing no I think it's great okay yeah that was that

was you know way too much explanation for how to exercise a mouse so anyway um we exercise the mice right so that works and that's great and then the next question for us was well you know what happens when we detrain them you know are they going to lose the muscle mass lose the adaptations that was the first question and if they do if we retrain them will they gain that muscle mass back more quickly so that's that was the first study we did we introduced the model and then we we basically just stopped the

mice from running after eight weeks we just clipped the wheels and they just hung out in the C and you know there there was a draining response at least in some of the muscles um which was some didn't drain others did so how long so eight weeks eight weeks fantry whe running and then how long did you D TR we did uh oh boy you're you're you're pushing me here I got remember remember eight got too many Pipers you can't remember them all yeah eight weeks of training and then I believe it was weeks of

draining um and then in one of my and that was the first series of studies was this the the training and then the dra trining just to look at that response and then we followed up eight weeks training eight weeks dra trining followed by four weeks of retraining so like a Shor yeah so um so yeah that was the original set of studies that we did and the first couple just focused on the training detraining then we added in the retraining component you know one thing I might say because people won't necessarily know this is

um you know they'll be sort of thinking about oh how does that relate to me you know as as a human and maybe just explain a little bit how about about how eight weeks for ER rodent is kind of like a long longer percentage of their lifespan sort of thing so because you know I I've often you know we talked of before I came on that I've done some studies in and rights with where that may have some sort of epigenetic um interest and people say oh yeah but that's you know that's only uh six-month

old rat I say yeah but that's like a four-year-old CH child for example yeah yeah that's you do have to contextualize it within you know the lifespan of that organism and so for a mouse or rat for instance you may get 24 months out of their life span two years or so depending um you can go more than that but you know at least in our hands that's about getting close to the m that's like uh 65 or 70 years in a human being the equivalent of 24 months so yeah if you train a mouse

for8 weeks that's like a significant proportion of their lifespan and so um and so yeah that that duration of training and draining is relatively quite long even though it's like a normal training duration for a study you might read you know where they use college students or whatever it's a semester right eight weeks so or 12 or 12 weeks so um so yeah it is important to keep that in mind where the the time scales sort of should be on how long the life of the mouse is so or that they're at yeah y y

point good point no it's good because yeah people might be thinking oh if I do eight weeks I'll get this and that and then if I do four weeks I'll get this and that but I guess that's why eventually you need the translation but it's very important so i' I've done the same as you where well I literally did the same as you did my masters at Paul State and then but but you know starting off doing human stuff and then doing more animal work you can look at mechanisms but then going oh can I

apply this to the humans yeah so so what did you tell us what you found then so eight weeks of training or or even if if it's more the the follow-up one so I saw your study here muscle memory um that was in mice why don't you tell us what you're finding generally with this training detraining training again to to muscle fiber types and and their strength and all sorts of stuff yeah sure so yeah when we train the mice for eight weeks we see hyper we look at the hind limbs right so we're looking

kind of at the the calf muscles so to say um and so we find that the muscles pretty much all of them we have like a fiber type transition towards what would be considered a slower twitch phenotype so theoretically more fatigue resistant um and then we see a lot of growth we see growth of different muscle groups in the the hind limb but then we dra Trin the mice some of the muscles will atrophy and their fiber type will change back to like their untrained condition within those eight weeks um some muscles won't though which

was interesting to us um like the Solus which is a more at least in humans more postural um type of muscle it's it's you know very fatigue resistant a lot of slow slow twitch fibers um at least in the mouse it has a similar sort of phenotype I I suppose you could say it's smaller it's different in variety of ways but fiber type wise um you know it's it has some slow twitch fibers in there and um that didn't actually detrain after like eight weeks and even and then we we extended it out I think

to 16 weeks in the follow-up study and we saw that the Solus didn't really detrain which we thought was interesting um still to this day don't have an excellent explanation for that they did put on some weight after the training almost as if eating more during training and I think they continued to eat more after training and they put on some body weight and that might have been loading the Solus to help kind of keep it trained perhaps but nevertheless the more fast twitch type muscles like the plantaris they atrophy back to their kind of

starting point and their fiber type switches back and things like that and so that's what we see there and so then that gave us impetus to go and retrain them and specifically look at the plantaris muscles since it went kind of back down to its original size to see if it kind of got bigger faster so when we retrain them was for four weeks so he originally trained them for eight washed them out for a period of time then just trained them for a short period of time and the comparator there was just a naive

mouse that didn't do anything except train for that four weeks AG exactly yep and so so when we retrained we found that the muscles grew about 10% more um with that retraining and so that was kind of the the the global responses to like the muscle mass and things like that um okay about some differences at the muscle fiber level as well as far as like fibers that were growing and getting bigger um relatively more than the group that hadn't trained before so there was some evidence for this muscle memory kind of um thing going

on in our mice which has been shown before in humans too and so um so that kind of gave us some motivation to to to dig a little deeper and try to see if there was perhaps an explanation for that okay so yeah if I just sort of summarize make people make sure people are clear because we sort of say fast twitch slow twitch and you did a good job explaining it you know the more fatigue resistant but just make sure people are clear so so as as as you said um the slow twitch fibers

are more sort of fatigue resistant so you tend to think of that more with people that are good endurance athletes often we do we biopsy the vast Salis which is the quad recepts but the one on this on the outside and you know the average person might be 50/50 but you'll see on average an endurance trained athlete that's that's good you know you might be Insurance trained but not very good um a good insurance trained person might be like 70% slow twitch so more f fatigue resistant not so good at sprinting it won't produce as

much lactate things like that and then a sprinter will be sort of the other way around they'll tend to have maybe 70% fast wi fibers um they fatigue very quickly but they produce a lot of force and um that's what you want right as a sprinter so just to make sure people are clear on that now you're saying that in your uh M this is mice yeah in your in your mice where they've done your resisted World running for um eight weeks generally they get they they're getting hypertrophy so bigger muscle size yeah some of

their muscles are getting bigger and you're finding when you drain them uh so when they stop training you literally lock the wheel that the slow fibers so those more fatigue resistant the ones that the endurance train people tend to help they actually tend to not detrain they tend to stay about the same and the fast fibers um more tend to go back to what they were yeah which is really interesting as you say really interesting and surprising and uh I'm still like hang on uh and and you said even when you wait 16 did you

say 16 12 or 16 weeks because we originally I think we originally 8 we dra train and then we saw the so did an atrophy and we thought that's curious did a whole other cohort of ice which takes forever think you know you train them you D train them all these things to 12 or 16 weeks I really should go back and yeah no it's fine yeah and which we say which is probably as you said as we talked about it's kind of hard to compare but if anything be longer in a human you know

that's a long time in a in a mouse um so that's really interesting but the other thing you said was that they tended to get a bit of a trans a um switching of their muscle fibers anyway so when you train them with this resistant wheel Runing they tended to get some conversion of their slow sorry of their faster type muscles to slow muscles so they're getting more slow muscle uh fiber types and those slow muscle fiber types don't tend to detrain sotus um that was that was true but in the plantaris we're still shifting

like when we train them the mice the plantaris muscle more you know type 2A 2B and 2x humans don't really 2B but we have the 2x in yeah but uh yeah so you know but usually any type of training whether it's resistance or endurance training you'll move away from having those really fast sort of fibers to more homogeneous either 2A in this case terce and that's exactly what we saw when we powert train the mice we start losing the two BS and X's start getting all right y shed back more to towards 2B and X's

when the planet terorists um ah yes y okay that's great so that that's actually a good little segue to to mention the people that they might want to listen to the excellent chat that I had with Will derave um yeah I that one that was really good I enjoyed that yeah exactly so if they want to understand more about this business so basically what he's saying there is what Kevin's saying is the cus muscle is mainly slow fibers and then the um the plantaris muscle is mainly fast fibus but they a lot of they've got

um so you've got fast 2A which is more sort of aerobic um but still fast and then 2B and 2x which is you go and have a look at um whim D's chat to talk about you know what what there is in in rodents versus Humans but basically yeah it's really interesting that whether you do endurance or strength training you tend to lose your two B's or two x's and they switch more to two A's so becoming a little bit more sort of slowish sort of phenotype slower relatively yeah yeah and more aerobic sort of

thing and um anyway so basically whether whether you're talking about your fast twitch muscle which is which is your plantus which is more fast twitch or your or your Solus things are becoming more slow more sort of aerobic yeah is that even within the plantaris because sorry within the cus because I know in humans and and rodents the the celus is a little bit different um the humans tend to be like almost all slow and I think in mice it's maybe 50-50 but you're saying you're getting more slow yeah yeah yeah like with the with

the power training we saw a shift well the Sol is as you say in the mouse is more 2A in type one like 50-50 is we'll just say and then you start seeing a shift more towards type one the thing is like and this is just an ongoing conversation in the muscle Community is like you know looking at fiber type as far as his twitch profile and fiber type oxidative profile they don't always match up perfectly because in the mous the two a tend to be very oxidative even more so than the type ones in

many occasions makes a little bit tricky um okay so let's make it keep it simple as as the way you had it and I've now sort of complicated it but yeah basically you become more type oneish whether it's type ones or two A's or something you become more sort of aerobic um with the now I guess that makes me think because I know I know we're we're going to talk about muscle memory but just the actual training itself it makes me think that the training they're actually getting quite a lot of the um you know

the aerobic sort of stimulus from the from the running on the treadmill it's not just the the hypertrophy which is um do you think if they were just doing the weight do you think if they were just doing the say the squat whether they'd get that sort of response or not I don't think you'd see that radical of a fiber type train you would I think see a lost of your more to and X hybrid fibers you may not see that full transition over um towards having potentially more ones or much um of ones but

yeah uh I don't think you'd see that that same the endurance component is playing a factor so they're running anywhere between eight and 12 kilometers a night when you're using younger female mice and that's a lot that is really impressive because we've done studies with with rice mice and rice mice and rats can buy them and get rice um and yeah 8 to 10 kilometers a day is is is is what they tend to do and they're tiny so it's again if you think about that for human is like running three marathons a day but

um but uh they're actually doing that even with the resisted wheel I that's incredible yeah well that was the beauty of the wheel that we accidentally sort of um Corey Dr dung and my colleague he we at the time all we had with these metal running wheels and you know to buy a they make special running wheels that are weighted running Wheels where it's like a break that you put on the wheel and you gradually increase the the friction with the brake on the wheel but then they get to a point where they can't even

move the wheel yeah yeah yeah stop running whereas we put the weights just on one side of the wheel and it made it kind of like lopsided and so it facilitated them running very high volumes um still with a lot of weight on the wheel up to like 20% of their body mass on the wheel they would still run this amount and so that was sort of the secret sauce with the uh the get it to work yeah not like it was something we had necessarily planned it's just that that was what yeah great right

so the muscle memory part okay which is the I keep getting caught up on these details because I love all this stuff um all right so the muscle memory bit right so you're saying about 10 so you're saying when they did the same well actually okay here's a question okay hang on so they got about 10% greater hypertrophy when you did it the second time than the first time so he's saying that's the muscle memory bit because they've responded quicker but were they doing the same amount of because one of the the great thing about

voluntary wheel running is it's voluntary you're not having to stimulate them and they're choosing it of their own accord so they're not getting the stress you know they get a lot of stress you put a put a m around on a treadmill you're making it run if plus or minus electrical stimulation we don't do that here we we just blow air on them but anyway it's stress for they hate it okay so then you get the cortisol and adrenaline and all that stuff which is not real life and it's and then you wonder how much

of your findings of the stress response and how much of the training and all this crap so went voluntary wheel running you haven't got that so it's fantastic and I'm a huge fan of it but yeah I'm just wondering it's also a bit difficult to match the training though so did they do the same training the second time fortunately yes um in our in our in that particular group they did which was great and I mean if you do a big enough group of my I mean these again these are hard studies to do and

they take a lot of time and resources and money and all these things but um if you had a large enough um cohort you could also kind of like match them one for one as far as their volume goes you're G to have a range of volumes in the they're not all just to run exactly 10 right like you're gonna get a range varable and so on average the ones that had trained previously that trained again they ran just about the exact same amount as the that were naive which worked out great very concerned about

this too and I think it was like ends of six per group at that point um and so I was very concerned that like oh they're they're all run way more because they they had already been exposed to the wheel they remember it they're gonna hop on just get right to it um but fortunately the mice typically take pretty quickly to the running wheel um in my experience usually after a couple days they they kind of figure it out um within a week they almost always do and so um and we give them a week

of acclamation too just to like for them to get back in their back in the groove so to say so uh so did run the same amount fantastic great question it's important question they ran different volumes what do you attribute hypertrophy to right exactly and you got and you got about 10% uh um more hypertrophy on average which is which is not massive but it's obviously came up significant with you with you and yeah yeah and it's not massive but it's also not I mean when humans resistance train like you're not going to see a

doubling of muscle size in a matter of weeks like you sometimes do with like surgical models of of hypertrophy for I um so it was more akin to like maybe what you'd start to see if somebody was resistance training sorry sorry I thought you meant 10% different um no they gain 10% yeah they gain 10% more than the than the the the naive gr okay um yeah so what I just out of Interest how much of a hypertrophy are we are we getting so so when you do the the first time do they get a

I don't know what percent and then you know how much are we comparing yeah we're talking about like I guess we'll just talk about in terms of mass like goist I think uh 20 to 25% and the planet is like 15 to 20 I think the Solus gets a little more activated with the running which I think makes sense because it's you know G to be uh a muscle that's responsible for plant reflection the plant the plantaris does that too but um the sius definitely gets uh gets a pretty good amount of stimulation from this

type of running so yeah about i' would say 25% on the Solus and maybe like 15 to 20 on so just to make sure we're clear because I'm slightly confused so so Solus got a 25% increase in muscle size yeah the first time and then when you said it got 10% more are you saying it got 27.5% okay so let's talk about the plant terce for this because the retrained so the retraining data was oh sorry yeah you're right you're right plant terce um I you know it's a good question i' would have to see

exact I'd have to go back to because they didn't it was only a four-week training so typically when you when we power train the mice we're just barely starting to see significance with hypertrophy exact four weeks in the naive state right so they're just starting to grow by four weeks so it's a very so I would say that if memory is serving they were probably like they probably grew like 13 or 14% or something in that four week and maybe the the naive only grew a couple percentage right because relatively short ter so maybe that

hopefully that clears it up but um but yeah so basically yeah if the naive mice didn't really grow all that much in the first four weeks hypertrophy that's substantial then okay okay get it and then yeah so it yeah I was thinking you was saying 10% so if you went from up up if you increased by 40% then the second time you'd increase by 44% you know 10% more I probably spoke so no no no that's good no that's a lot then that's a lot so you're saying it's actually substantially more the second time with

the the muscle memory side of things and the I think the remaining question is like you know is it that they'll just they just hypertrophy more quickly or they'll ultimately hyper more sort of the that they would just hypertrophy they would just get to their Plateau faster right so maybe by eight weeks they the muscle mass would be the same between the naive and the the um exct prev group it's just they had a steeper curve or steeper that was what I was gonna ask you but I guess you haven't had a chance to look

at that yet um you haven't looked at the time course we didn't train them out to8 weeks CU for our initial question we really just wanted to see do they grow back faster and we that was what we were scared of if we went out to eight weeks we might have missed our time already yeah exactly and so we're like okay we'll do half the time yeah nice stuff all right so I can't let you go without this uh why do the slow twitch not um SAS why do they not okay so I'm sure you've

looked a lot of things in here uh in the muscles so is it that they didn't hypertrophy so I'm just trying to get my head around how it is 12 16 weeks that this that you stop that you do the draining and they don't drain the solely so the one that's more slow fiber slow Vena type even though it's bit both um what hang on so what did didn't they do sorry so did they not hypertrophy did they not uh change their fiber type back again do they not do anything I know you measured micro

R and all sorts of things did nothing really change so when we train them for the eight weeks the Solus again will grow pretty substantially let's just say 25% I don't know it's it's in that range um from Baseline and so but yeah when we looked eight and I believe it was 12 or 16 weeks 12 we'll just say after the we stopped them from running everything we looked at at least histologically was just the same like the fiber type you know they picked up more type one fibers and during the training and they retained

those for the dra train their fibers got bigger and they just didn't go back to being small and gained more myonuclei so muscle fiber nuclei from the satellite cells which we can talk about they picked those up during the training too and then they didn't lose them during the wow it was like just a universal like just whatever they got during the training they just kept and they also again put on body mass during the the D train they said that yeah and I think it has something to do with I know the college athlete

effect right like you're super fit in college you're eating all this food to support your mass and to support your aism and then you get out of college and you stop performing at the super high level and you continue all right all right but I think we have to say in humans you you don't get this so if we forget about the muscle memory if we just look at humans that have done weight training or endurance training and then you they detrain I think it's fair to say you don't get you wouldn't keep the muscle

mass you wouldn't keep the fiber type changes and things think is that so is that a species what do we make of that I guess yeah it's I've thought about it of course and you know it's hard for me to make heads or taals of it but I guess one thing I could say is that like it probably depends very much on the muscle and the fiber type percentage and probably just the the function of the muscle that you're looking at when you think about the the Solus for instance like if people put on fat

M they get larger they eat a lot and they become you know or whatever a lot of times their leg muscles their calves specifically will get bigger yeah and so it could be and that's probably mostly Solus because the postural muscle and it's just being loaded heavier and heavier every single step for their whole lives and so yeah I guess it would make sense that's a fair point that's a fair point because when we when I talk about humans so if you did go back and look at every human study that's looked at training and

fiber type changes and whatever almost all the training stuff that's been done in humans has been the the um the vastis which is which is you know again the quads which is not really a strictly a postal muscle and then if you do look at Runners you often biopsy the um calf but it's the gastr it's not the Solus more and more people do look at the Solus now so I think that's that's a good fair point I I guess I'm willing to uh to pay that because Solus is like as you say a postal

muscle so so these muscles that are closer to the bone that sort of deep muscles not The Superficial ones tend to be postural so you know we talking about walking around and things like that so yeah it's possible that that there may be changes that that you know I guess hasn't really really been looked at that much in humans I guess yeah like training and then dra trining and looking at the Sol no I don't think so um if it's out there that I it's probably more in the context of endurance training we're talking about

resistance here and so and um yeah I mean the Solas is at least for the human beings for their low it takes up a good I think it's the bigger muscle of the calf I'm not than than the G I think it's bigger um but it lays underneath you know the gas stro and so it's a little harder to access and when you biopsy it as you probably know you going from the side um you know you have people laying on their stomach going from the side I think I had one of those when I

was at Ball State even a Solus uh I'm pretty sure I did I don't remember I had a lot you know it's classic I can't say this without so we're talking about Ball State right so I was at Ball State and and um it's fantastic so people if they Haven haven't had a look they need to have a look at David cost's chat with me so longest one so far and I just love that guy anyway so he was you know he is all state basically until he left he finished and then Scott trappy your

supervisor took over but anyway I have to say you might you might might like me saying this but he told me how he biops it himself one day yeah he stood there put his put his leg up against the chair and buy up se's Cal he didn't do a Solus as far as I know but anyway yeah that's that's fun yeah that's sounds like something doc would do yeah great stuff all right so if we start thinking about mechanisms then yes so maybe if we can talk about um you know you've touched on satellite cells

and things like that maybe if we just talk about seeing as the title of this one is epigenetics uh and muscle memory we just talk about you know genetics versus epigenetics what is epigenetics just a bit of a background we've talked about it before on the podcast but people may not have seen it and and you know what we're getting at here because it used to just be everything was genetics right Charles one genetics there's no nothing else and now we're thinking more about epigenetics as well epics and genetics so do you want to just

explain that a little bit Yeah I think like in layman's terms I guess the way I would think about epigenetics versus genetics is like genetics is like can you express the Gene and epigenetics is like will you express the gene you know like so it's a it's a it's changing gene expression without an alteration to the genetic code so it's like yeah we have all these genes like all of us have these genes and they get turned on and turned off in response to various things but what controls largely that turning off and turning on

of of genes is the epigenetic layer which is the things that are kind of either impeding or making the genes available to be expressed and so that's really kind we're talking more about kind of a regulatory layer on top of genetics that when we're thinking about genetics versus epigenetics we're you know just a lot of times thinking about epics being the intent so like is the gene going to be expressed um so turning it off off and turning it on we have it but it needs to be turned off or turned on the epigenetic layer

kind of controls that and it comes in a lot of different flavors like talking about histone modifications and and DNA methylation and some might even qualify micr rnas as as part of that conversation and so so yeah it's uh that that's the way I'm thinking about epigenetics is what's controlling whether a Gene gets expressed exactly but can I also add another layer so the Charles Darwin type thing is um the classic thing which is you know if a giraffe has a long neck you know is it because it's been reaching up its whole life or

is it because you know the father and the mother had long necks and then it got passed on and the other thing about epigenetics is you can actually pass it on so so it's the controlling during a lifetime but also um you know things that you do during a lifetime can be passed on even though the genes themselves aren't changed the likelihood of them being expressed in the next generation is passed on so so I just wanted to make uh bring out that distinction so people might want to see um lorri goody years's chat on

here um and I've done some work on that as well where where you can for example have a so we did like a high fat fed father and then you know The Offspring is more likely to get diabetes and then she's even looked at the next next Generation now so so that has to be epigenetics exactly it has to be epigenetics because you haven't changed the genes so but as you say though also during your lifetime so an example that that that sometimes you think about is is people that have uncontrolled diabetes so they've got

elevated glucose for 20 years or something and then they control it really perfectly for the next 20 years they still have worse outcomes than you know than people that have had um good control good control the whole way so it's like okay something happened early in life earli in their life which is still having an effect later yeah is that fair to say those sort of distinctions yeah yeah I think so I mean I think about it in that context mostly with exercise you know like I'm talking about what's happening within your lifespan what's happening

in youra cells within your muscle cells so not like your germ cells um so yeah that's uh that's definitely how I'm thinking of things but it's the opposite like you're thinking about diabetes and perhaps bad outcomes and I'm trying to think about more about good outcomes like what are the good things that it's that it's that it's you know imprinting so or something into your uh your epigenetic code to to make it beneficial throughout your whole life even if you stop doing it you know yeah exactly yeah exactly well we actually well it's not about

my stuff we did a thing of if you were born if a rat was born small or if the father had high fat diet you exercise The Offspring from just five weeks to nine weeks of age and you fixed a lot of their problems so that was really cool yeah so it's really cool but yeah so yeah exercise is great couldn't let that one go so yeah so you're talking about here a situation where they they do the exercise they get an adaptation they drain and then they train again and they get a quicker or

we don't know if it's quicker I guess but a greater response and and and how do you tie that in maybe with epigenetics yeah well I mean I think I would be remiss if I didn't talk about like the the cellular foundations of what muscle memory is thought to be which you know there was a lot of work done 2010ish in that that time frame early before and after that um a couple years but uh a guy named a Christian Gunderson who kind of laid the foundation for our knowledge in this for like kind of

what what's what what causes muscle memory and he did a whole series of different studies using mice and rats looking at the number of nuclei in the muscle fiber right because muscle fibers are multinuclear they're not monuclear cells like most of the cells in our body they're these long cylinders and they have hundreds to thousands of nuclei in them and those nuclei are thought to not divide um whether they're postotic or you know whether they can synthesize DNA you had Benjamin Miller on here so he talked about that I'm sure but um but yeah whether

or not they can divide and replenish themselves I think is pretty established that they can't do that and so um but you can pick up you can gain more nuclei within a given muscle fiber from your stem cells and usually when the muscle fiber grows a stem cell will become activated and it'll fuse into the muscle fiber and add a new okay just go sorry just go a little bit slower so this it's kind of hard stuff so yeah just you're saying that most cells so if you look at your cells in your gut or

whatever they'll have one nucleus yeah that contain the DNA and you're saying muscle skin cells and our muscle cells you say have hundreds of thousands hundreds to thousands yeah like yeah I thought that made more sense I thought you said hundreds of thousand hundreds thousand yeah hundred to thousands of nuclear so more so it's really interesting so each cell that contains all your DNA yeah so H nucleus that contains all the DNA for your body is is replicated many many times within the one muscle cell yes and then you're saying um this replenishing them and

things like that so maybe just go there but just go a bit slower and um okay and then say what happens with resistance training and things like that yep yep so so within the muscle fiber is going to be many nuclei so all of the copies of the DNA there's numerous nuclei that have an individual copy of you know all your DNA in each one of those whereas a normal cell a skin cell an eye cell whatever is just one small cell that has one nucleus in it so it just has like one complete copy

of your DNA the muscle fiber on the other hand might have hundreds or thousands of nuclei which means it has hundreds or thousands of copies of your your your DNA which is crazy it's called a cium and so it's you know just uh it's multinuclear and so all these nuclei are having to work in concert to regulate this to think about yeah yeah usually voluminous I guess the big volume the cells have big volume they're very very large cells I mean a muscle fiber you if you pull out an individual muscle fiber you can like

see it with your eye whereas like an individual skin cell you can't do that like these these muscle fibers are massive and they have lots of nuclei and it's thought that these nuclei are what help support their their size um you know because if you only have one nucleus for a what I'll call a super massive cell it probably wouldn't be able to control the entire cell it would you know probably cell would die or it be very inefficient um and so yeah it's uh it's a really unique one of the thing one of the

very many cool things about muscle is the fact that it's this big each fiber is a each cell is a big multinuclear sens it's it's funny though because when we're talking about these big cells I still want people to understand how small these things are so for example when you have a muscle biopsy which we talked about and I've at 33 of them you're taking out we we often say like two or three rice grains size you know um you know which is actually quite a big sample but I remember when I've done fiber typing

on my when I've had fiber typing done on on my muscle one biopsy it was I remember one was 572 muscle fibers you know because you have it on cross-section and you cut 572 muscle fibers so I want people to realize that even when you have a couple of rice grain size there's 570 fibers in there so when we're saying these are Big they're big compared to other cells but everything's like tiny you know so when you think about these tiny you got 570 fibers in in this one biopsy and then each fiber has hundreds

to thousands of nuclei it's just like hang on a minute so it is mindboggling mindboggling yeah I remember my mom my mom at one stage I said to her how red blood cells I I said there was six million red blood cells per cubic millimeter and she's like hang on what and I'm like it's my I don't want to hear it blew blw away oh yeah cuz then I said each red blood has you know all these millions of hemoglobin it's like oh no go away so yeah it's it's it's it's kind of fun to

think about okay so these muscle fibers are big in compared to other fibers compared to other cells things I guess yes and they have all these nuclei now why is that important and and how are we going to fit that back to muscle memory and things sure yeah so I mean it's important I think that these muscle fibers have all these nuclei because these nuclei are like they're the control centers of the cell right they're all the of every cell they're the control center of the cell so they have all the DNA which means they

express the genes which become the proteins that then become the structure of that cell in function of that cell as well and so um so yeah having hundreds to thousand of these nuclei mean that like each little each nucleus has to kind of like govern its own little area so to say the myonuclear domain right and so like maybe there's a hundred nuclei in a given muscle cell and each one controls the area like immediately around it and then the one next to it picks up and controls the area that's adjacent to that one just

so that you can have like an even distribution of Gene products proteins mrnas all these things and so um and it's thought that when the muscle grows that you have to add in these new nuclei um because the nuclei can't replenish them they can't divide they're they're what we call postotic and so they you know you can go listen to Benjamin Miller's talk and he'll say some things but for the most part they won't divide like we don't think they're going to divide they can May synthesize DNA but they can't divide themselves so if the

muscle were to grow and you needed a new nucleus because the muscle got bigger um you'd have to fuse that in from a stem cell or a satellite cell and so uh and there're these cells that all of us have them and they're responsible for injury repair if you like really severely injured your muscle the stem cells would activate and would rebuild the muscle but if with exercise for instance if you're growing the muscle like with hypertrophy those stem cells would activate and they would donate their nucleus to the muscle fiber so that the muscle

fiber can continue to grow and so that's sort of the the thinking um and whether or not that process is necessary for hypertrophy is a long conversation and so I spent a long time studying that um you know during my postto and so um and there's a lot of different opinions so we can go there later if you want but for the purposes of muscle memory though um and as you said Benjamin Miller talked about that stuff as well he said if he inhibited satellite cells um you know he got this and that so people

can go and look at that but yeah for the purpose is of and we can do that we can delete the stem cells from the muscle alt together and do all types of things it's very very cool so um but yeah we can definitely talk about that if you want but um so for the sake of muscle memory though you go to the gym you lift a weight your muscle gets bigger eventually those stem cells fuse in and then you end up with a bigger muscle fiber that has more nuclei in it and that's supposed

to be to help your muscle to continue to grow and adapt um and so back to Christian Gunderson he did a lot of work in 2010 around that time frame using Mouse models rat models using anabolic steroids using uh different sorts of resistance training analoges and rodents and and he came up to the conclusion that when you gain a nucleus during hypertrophy uh if you were to stop training and that same muscle fiber were to atrophy that nucleus you gained he said wouldn't go away so it's a permanent addition to the muscle fiber and because

when you start training again you start with a higher Baseline of nuclei fibers that then you'd be able to grow back more quickly and I think you know that's that's it does make sense I think that's a very intuitive uh sort of thing that he was able to experimentally in his hand show that that's how that worked and that was interesting and so we but a lot of the experiments that um that looked at that specific sort of mechanism they used surgical models of overload or used again an and different things like that so we

wanted to approach it from a more translatable perspective with our power model right so train the mice and we can derra them and there's no surgeries or drugs or any of these things and so when we did repeated the study doing training D trining with what would be a more translatable model we didn't find that to be the case we actually found that the nuclei we don't know how but the nuclei that you gain during hypertrophy seemed to go away during the dra training so that we found that like it went back down to Baseline

levels which is more pleasing to me anyway because because your whole thing about I was thinking about we have a thing around here called neighborhood watch you know where the people you know keep a watch on their neighborhood and it was it was making me think somehow that each you know each my nuclei so each muscle nucleus is watching its own neighborhood right it's looking after its own turf right but then if you expand the neighborhood then you need more neighborhood watch but if you shrink it down you don't need it again you know sorry

we don't need you guys and it makes more sense that you that you get rid of the extra nuclei than than you keep them because it it doesn't fit with the whole point that he needs x amount of nuclei to look after their own area right and it I mean the myonuclear domain as you are sort of expressing right now you know it works both ways you know it probably works with hypertrophy when the muscle gets bigger but also with atrophy too you would think and I don't know if the time scale always matches up

you know like I think probably the muscle fibroid atrophy quicker than you lose a nucleus and we don't know how you lose chicken in the egg yeah we still trying to kind of unravel that and there's people that are going after that question I think it's fascinating if that process is happening how that occurs is like is it apoptosis of individual nucleis and nuclear autophagy some like there's a lot of Yeah well yeah like with apoptosis So when you say terms like a just say what that is sure yeah like apoptosis would be cell death

but in a cium so when you have a muscle fiber that has hundreds of nuclei if you just lose one nucleus well the cell's probably not gonna die so it's like it's it's nuclear apoptosis I guess and so but um how that process might occur is is very much a mystery I think still at this point all right so you're saying with sorry but with your see when you do the strength well the the running wheel which is overload so kind of strength training they get more they get hypertrophy and they get more myonuclei or

more muscle nucleus which makes sense but then when you D train them you said unlike Gunderson is it Gund you didn't he kept his kept in myclear even with d trining so when they they lost their hypertrophy but you didn't lose yours is that right and that's that slow and fast fibers the plantaris muscle we did not see and the Solus again they didn't the muscle didn't detrain so in that in they stayed that's a nice control then that's a nice control for your for your model in that sense yeah yeah because you might say

ah there's just technical differences or something but the fact that you you had the solers that didn't dra Trin and they kept their my nuclei and the plantars that did dchain and they lost in my nuclei that's nice control and we did that several different ways too we isolated out individual fibers ENC counted nuclei like longitudinally on the whole muscle fiber part portion of the muscle fiber and we did it with hystology as well which is another popular way to like measure these things and so we did it a couple different ways we got the

same result so our um conclusion from at least these Mouse studies was that that this hypothesis may be a little more nuanced um maybe there's more conversation to be had about what a potential muscle memory mechanism could be because if it's not a maintenance of the myonuclei that you gained from hypertrophy perhaps it's a difference within the myonuclei that are there um that was kind of our thought proc maybe could be Rel okay all right so I man I managed to sort of confuse things slightly there so I think it's nice sorry you're finding that

you have Hy pery you get more my nuclei and then you if you detrain you lose it makes sense in terms of the myclear domain and looking after the neighborhood and all that but it doesn't help explain your muscle memory thing so you were saying you were thinking as Gunderson showed I guess that that yeah if you train you get more myclear you D Trin you lose uh you you keep them and then you train again so maybe that's why you do better so you're saying because you didn't see that it seems like maybe that

is not the reason in terms of the number of my nuclei but maybe the my nuclei that are already there are more sort of ready to go yeah more ready to express genes yeah yeah that was our hypothesis and that was you know kind of the the hypothesis that I mentioned Adam Shar when that's what they were looking they weren't looking at nuclear numbers they were looking at epigenetic changes epigenetic perfect so that brings us to epigenetic so then you're saying okay so maybe there's epigenetic changes so that the the genes that are there you

don't have more total genetic material because you don't have more myonuclei but the myonuclei that are there so the genetic material that's there already is more likely to turn on so so or quicker turns on quicker or or to a greater extent in response to the second lot of training yeah so the muscle mem that was sort of our our thinking yeah that's what we wanted to kind of get track now do you have any evidence for that yeah so we did a study to kind of try and sus this out a little bit where

um we were interested in looking at the myonuclei now but interested in doing some molecular measures of them you know so not necessarily counting their numbers but isolating the nuclei out and then doing some different sort of ass say okay maybe there is like a epigenetic and EP memory of the of the previously trained state that remains when you are retraining and so we uh we had a mouse model where we could genetically label the muscle fiber nuclei the myonuclei with a a green fluorescent protein so just just to make them turn green so that

we could identify them and we just do some different biochemical sort of assays to isolate out these fluorescent nuclei and then we looked at the epigenetic profile of the myonuclei um after the draining period to see if there was like a a memory of of what the training State looked like at the epigenetic level so looking at like essentially Gene accessibility we'll say for in layman's terms and found that yeah there were some genes that kind of had a profile that would be suggestive of they still kind of had their their trained phenotype so to

say so they had epigenetic marks around them that would suggest that perhaps they could be activated more quickly or more readily to help facilitate a retraining response that would maybe drive um greater hypertrophy with retraining and this dovetailed with other work done by Adam Sharpes and some other folks that found a very similar thing that there may be this memory of the train state in the myonuclei presumably but also that you know there could even be like a like a more dramatic gene expression like response with the retraining that would help facilitate the muscle growing

back more quickly and so that was kind of in Broad Strokes what we what we sort of found with uh with these studies that we're doing and we're still kind of going after this and trying to understand on a deeper level like which epigenetic layers potentially could be important for you know driving regrowth um and we actually we did all these studies with looking specifically at the myonuclei but we did some other things too where we were looking at like different types of transcripts or messages that are produced by the nuclei and we found that

there's a specific micro RNA that also stays repressed during the draining period so when you train this micr RNA goes down I can tell you what a micr RNA is but um it's basically a small a small um RNA that binds to other larger rnas and caus them to not get turned into protein or to degrade um so basically is a way of fine-tuning what gen get get made into proteins um we found that there was a change in this microrna profile that was persistent throughout the entire draining period um so out to like 12

weeks and we thought that was interesting and that it may be related to how the muscle is more responsive to the retraining and so we did a couple different things and we're still not 100% sure it's hard to link these things mechanistically right these are associations still even though we're doing kind of some sophisticated molecular work I do a summary thing just before you go that next to I just want to make sure people are okay so just want to make sure tieing again because the epigenetics thing is still a bit new to people so

you know how we we talked earlier about um how you know your genes don't really change during your lifetime when they don't get changed passing on you know Generations but the likelihood of these genes turning on so so there these epigenetic markers yeah so you know you touched on a few things earlier but we won't get into that too much you know methylation and all that so these epigenetic markers may still which which affect the the likelihood to turn on or turn off it sounds like some of those and ones that you think are important

by pery they the genes that are that are important for I pery some of them have these epigeic markers on them still after the dra training yeah and they didn't change so then it's more likely they're going to turn on again is that what you're saying sure I think that's a fair assessment yeah I think that's uh sums up pretty well y all right perfect and and sorry can I say do they turn on more so when you have these you got okay this Gene has a mar on it that makes it that we think

is going to make it more likely turn on again but then when you do the draining the retraining so when you go and train them again do those genes turn on again and uh and our study ours wasn't for the mouse studies we weren't didn't set it up to to answer that question because we didn't have like an an acute exercise bout in each state so we didn't have them like do a a bout of exercise and look at their gene expression response um it would have just been we would have had to kill too

many mice to pull that off and so we just looked at the ultimate outcome but other studies like um Adam's study did not mistaken show that some of those genes that have those that memory are more responsive in the trained State too like of exercise and that's probably really where it's coming in is like each bout of exercise you're getting that like little extra something from uh having that you know epigenetic memory that's ultimately contributing additively to the BG yeah this this actually reminds me because you know my main backgrounds being glucose metabolism and it

and it maybe explains the thing so there's a glucose transporter which I know you're aware of I'm just telling the audience called glute four so you know it moves to the membrane and brings in glucose yeah so when you contract the transporter moves the membrane brings in the glucose it can also do it in response to insulin insulin GL for moves the membrane brings in the glucose right yeah now the interesting thing is that each B of exercise your glute four expression goes up and then comes down again but it tends to be kind of

additive so you know it's going up so if people aren't watching YouTube they won't see the um a lot of people do Spotify but you know it's it's going up it's coming down but not all the way down again and then you do your next Bel it comes up and it goes down but not quite down again and this is the the messenger RNA which we sort of started talking about so the gene the DNA gets converted to message well it turns on messenger RNA which then causes a protein um okay Transfer RNA and then

you end up with a protein which is glute 4 and this message from each Bel the messenger RNA it's going up and then coming down so anyway it's not going down so I'm wondering you know maybe that's an example of epigenetics so the fact that training is you know sometimes we say that training is a series of single exercise belts right and it's always I've always thought about this and I thought hang on a minute but it's additive so maybe this epigenetics going on there so I don't know if you want to say in your

own words what you were starting to say as well to fill in the gaps for people just like I tried to fill in the gaps maybe you fill in some more gaps yeah I think it's probably like as you say related to that like every exercise bout is contributing to the ultimate outcome and like yeah with each exercise bout if you had if you started in a slightly different we just say more favorable place epigenetically you're able to access those genes more quickly a messenger RNA that then becomes a protein so you ultimately end up

with more of the protein after each repeated bout and then you get a greater adaptive response after a period of time so eight weeks 12 weeks what have you and so yeah I mean that's I guess intuitively what I would think is happening but I haven't tested that specific hypothesis but I can kind of draw from other areas of literature other studies to point that that could be prob a potential explanation and it could be related to epigenetics it could be related to these changes in micr rnas or maybe longlasting it could probably if I

had to guess some memory is probably happening at a variety of different levels and how long that memory lasts is yes other can of worms I don't know right and that's partly why I kind of pulled you back a little bit because I just felt like we might have been getting away so I I don't want to um cut off the micro RNA bit but I just want to make sure people were aware you've got the DNA the messenger RNA the transfer RNA and then you end up with the protein why don't you tell us

now just again kind of basically what the micr RNA business is and what you found sure So within this the the framework of the study design with the mice have been talking about so we train the mice and then we detrain the mice um and then we look to see what things are potentially long lasting after the training has ceased um and we measured a variety of things as you say mrnas um but another thing we looked at was micr rnas which are basically these really kind of short rnas that um get generated you know

from the same genetic code from our DNA they come from there and um sometimes they even embedded in other genes and they get processed and become these little kind of like free floating little um rnas that can then go interact with the messenger rnas so they basically kind of have a mate or maybe a lot of mates because it's a little sequence that it is comprised of and it'll go and interact with a messenger RNA or maybe a lot of different messenger rnas and either stop them from becoming proteins um by preventing them from being

translated or degrading them so they don't have a chance to get translated and so it's sort of a way to to fine-tuned so you may Express a gene and that would be signal intent for it to become a protein doesn't always right it's not a onetoone like a gene get Express becomes a protein it's not like always that linear there's some Nuance there um but it's another way in which like okay let's say a gene got expressed but then the cell didn't need it the micr RNA could come in bind to it signal for it

to get degraded and it doesn't become Protein that's that and so um but we can we consider micras generally to be repressors um you know because they're going to shut down the translation of a specific mRNA um it can have a variety of different biological effects of course but we found that there was a specific microrna which is enriched in muscle um specifically it's called a myomir so myo the prefix being micar Mir we found one of these myomir went down with exercise training and then it stayed down for like a very long period of

time after training we think that micr RNA could have been like serving as a break on certain transcripts that were related to growth and then if that break is already off when you start training again it could be easier for you you know response so another kind of molecular layer which this retraining response muscle memory response could be working and like I said I think it's probably working on several different layers okay and and as you said micr rnas have lots of mates so they they tend to affect more than one gene or protein again

did it make sense you know like when you actually look at the proteins I mean in some ways it's easy to say oh this was down therefore whatever but did the proteins that it interacts with did that fit with your hypothesis as well well because it's mere one and it see seems to Target things that are specifically related to growth like igf1 and different like or sort of proteins yeah the fact that Mir one was down was could have been indicative of that it was serving as a break for some of these growth oriented processes

but then you just remove that break and then when you introduce the stimulus exercise retraining then the muscle can sort of take off again so we did we did hypothesize that we did present that as our explanation but okay we some computational analysis but we didn't go and um and actually now we have a way of testing this so this is something I'm actively working on but um but at that time it was just a hypothesis it still is to an extent but we are working I think it's really cool stuff really cool stuff now

you emailed me at one stage saying um you're introducing a new mouse model which we've yeah we've discussed and challenges some widly held beliefs on muscle memory so maybe just circle around again so um so you're saying it looks like it's more maybe epigenetic and not so much the myo but as you say there's poly layers of what are we what are we challeng here that the hardly take us back to the widely held beliefs with muscle memory the widely held belief I think was that if you gained a nucleus from a satellite cell that

was permanent like so if the muscle atrophied you would have like a hyper well call hyper nucleated muscle fiber so 100 nuclei maybe now it has 125 but it's still back to the size that it was but it just has more nuclei so it can take off faster when you retrain and I don't want to discount that hypothesis I think in some instances that could maybe it's muscle type dependent maybe it depends on the age at which you started exercising so if it was like a younger animal that you exercise maybe that's when that mechanism

becomes really operational there there's a lot of considerations here I'm not trying to discard that hypothesis yeah another thing sorry another thing yeah I realized we pretty much cover that another thing I realized was um I guess with we're doing a very DNA Centric um although you did touch on breakdown as well I I wonder if there's other epigenetic things that are going on so you know we've we tend to talk you know same when you talk about protein synthesis you tend to think about when you think about protein levels you tend to think about

the synthesis and it's like oh it's a bit harder to measure the breakdown you know so I'm wondering if it's the same thing I'm wondering if it's the same thing here where we it's maybe a bit easier to think about the syn synthesis of the protein and not the breakdown so wonder if there's an epigenetic thing going on as well with the muscle memory where your lome or you know or or even breaking down we haven't talked about the mitochondria but just the the breaking down side there might be a memory so it's like okay

we've made these proteins let's not break them down as quickly the second time right it very well could be um I mean I would be inclined to think that if you did lose a nucleus you would maybe lose some of the other like because you can lose mitochondria as you kind of pointed to like yeah I mean if you stop training you lose mitochondria um and I think it stands to reason that if you stopped resistance training you could lose a nucleus too I mean mitochondria have their own DNA as well true and so um

I think DNA or nuclei could be the same um yeah I mean it could very well be related to some breakdown process that I haven't thought about but I'd be inclined to think that the muscle would probably be maintain containing something in the DNA um because there's so many nuclei guess goes back to DNA but I guess what I'm getting at is um the the muscle memory part that maybe the lomes or whatever it is it's breaking down proteins maybe they have a memory you know what I mean oh yeah so like maybe they less

likely to break it down yeah potentially um I what I guess what I can say with muscle memory from what I've read I don't think people have really done much well I guess in the sense that like fiber type changes back at least in the plantaris changes back to um you know its Baseline phenotype and that's a protein measure when we measure fiber type um yeah I don't I don't know I I just don't know enough about that nor have I seen any evidence to suggest just something I threw out there I want to go

out on a crazy limb because I really don't know no I'm not suggesting you know that but I'm just I guess well you know like like I said with with protein levels for years and years it was just protein synthesis protein synthesis prot synthesis but but then it's been like oh hang on what about the breakdown you know so just to make sure people clear what I'm talking about so just say you do weight training you get an increase in your uh muscle mass your hypertrophy you say oh there's been an increase in muscle um

protein synthesis but in theory you could get an increase in your muscle mass by just not changing your protein synthesis but reducing the protein breakdown so I just to make sure people are clear on that I think in that instance though like at least with that example though like you you do want of course you want protein turnover right like I think it just from you know Global Perspective like you know keeping bad stuff around they don't want to keep that stuff yeah that would would it could be counter potentially and that's just more for

like the audience you know like yeah you always need be two size these equations so you could absolutely reduce breakdown but that might get you an undes what's probably more likely happen when your hypertrophy is you get an increase in protein synthesis and maybe the increase in protein synthesis is greater than the increase in Breakdown and then you get bigger yeah okay when you eat ex now yeah exactly now the other thing I I guess I wondered about was um I guess it's too early to know but you know if you strength train and then

20 years later you know and then you stop and then 20 years later you do it again in this there this muscle memory uh and then if you urance train 20 years later you do it again do we know the you know which is more likely to have muscle memory you know strength versus endurance or and also I guess we touched on earlier how long you know it might last so if you stopped for 20 years 30 years five years six months yeah so I think to answer the endurance versus the resistance I'll speculate um

the studies that have looked at the memory from endurance training versus the memory from resistance TR I think the Studies have shown looked at like memory either like the transcriptional level or even maybe at the epigenetic level don't show it to be as prevalent as what you get with resistance training now I will admit that my power model our power model combination and so but I'm based on inferring from other literature would would think that it's perhaps more the the consequence of the hypertrophy component as it is from the endurance component at least that's my

sort of Leaning at the moment um so I think maybe the memory component could be more linked to a hypertrophic sort of stimulus potentially um and as far as how long which is I mean a very relevant question um and the answer is I'm not sure because no one's done like a Time course in humans but I can say that at least back to our closing the loop on our conversation as far as the you know the lifespan of a mouse you know when we drain a mouse for 12 weeks that's like a long time

in the life of a mouse and still see some of these things persisting and so yeah I'm looking at the study design of the muscle memory study and we detrained our mice for 12 weeks and then retrained them it was 12 weeks and so um that's a pretty long time in the lifespan of a mouse now how that relates to a human being I I don't know and I think that comes back to those anecdotes that maybe former athletes say where it's like ah I was you know I was an athlete in college and then

I stopped and I got into the Working World and I didn't you know lift weights forever but then I got back in the gym and it's like you know second nature and the muscle came back exactly I don't know that's anecdote so take that for what it's worth I guess you got a million studies to do but it would be nice if you did a running wheel without the weighted because again I'm showing my endurance buyers here um and just see if they do have that muscle memory because part of me thought well hang on

maybe it's more likely to be endurance because the slow fibers didn't didn't go back you know what I mean the fast fers yeah for sure yeah no it's a fair question I've been told many times before why don't you have a non-weighted wheel I was like because I only have no I think it's good and you would maybe wouldn't have got if you did a non-weighted wheel maybe and it and it only really happens with with weight training you may have missed it right so I think it's I think it's great now the other I

just realized the other thing so when we talk about these you know uh just to explain more about the lifespan of a of a ro versus a human so because we're often doing developmental stuff so we so the rats for example so give people an idea the rats would wean at three and a half weeks okay so humans do not wean at three and a half weeks six months or something so just to give people an idea of the difference and their total lifespan is about two years or something um which is obviously very short

so just just again backing that up now I wonder the other thing I guess is how much training do you need to then get the muscle memory effects so obviously if you just did one belt you wouldn't expect you know that the even if you get epigenic markers you probably think they'd wear off you know so again it's like the more you do the more likely you get get the muscle memory I guess that would be my inclination but I mean even I'm not going to say an acute bout of exercise long is enough to

see this longl lasting change but an aute out of exercise can change epigenetic marks it does evidence for that and so yeah I mean how many it takes to like lock in I guess the epigenetic change if you know there is a longlasting one how long it takes to lock it in I don't know it's a good question um I mean at least in our study obviously with the power train they were training a lot you we said that 8 to 12 lot but you human studies that have done this have been much more reasonable

like you know three days a week of resist training you know three sets of 10 type of you know they still see some of these responses so you can scale it back relatively pretty significantly and still see some of these responses but as far as like you know would two weeks of five minutes a day of hit be enough like high intensity interval training or something like that I don't know people haven't done those studies yet that I'm aware of so yeah it's think things complicated is um is specificity because you know we know if

you do weight training vers versus training it's very specific so if you did like isometric so where your muscle not not um changing length I think it's been found I I know it had been found I don't know if it's been backed up later on but you only get strength gains in sort of like 10 degrees either side of that like you don't get it throughout the full range so I'm just thinking you know and then more specific stuff like Ecentric contractions versus concentric contractions and things like that you tend to get specific adaptations and

it's hard to think how that would fit you know what I mean like like you wouldn't how would you pick that up in the muscle fiber to then go oh I did concentric training which is muscle shortening and then 10 years later I did Ecentric training do I get muscle memory you know what I mean yeah that would be exceedingly difficult I don't know I have no idea it's pretty cool to think about that I wasn't expecting you to know the answer to that one but just just I think it's just an extra layer of

um complexity all right so what are we going doing here just want my notes I think we've got through quite a lot it's been great actually I've enjoyed it uh do you have any thoughts uh other stuff we haven't talked about or ah now I I this I this this are my notes and you actually nature or nurture or nature and nurture now I reckon that that is very cool so talking about so nature sort of genetics nurtures your epigenetics you know in the way that we've been talking because I always thought because it's the

best journal in the world is called nature yeah and then you talk about everyone always says is it nature or nurture I reckon a great Journal would be nature and nurture so gentic counter just nurture and then maybe nature yeah so anyway I thought that was kind of fun um okay so we we covered everything so another thing I was going to mention I guess the the epigenetics thing the classic is the Dutch famine so people want to think about something you could maybe relate to more so during the second world war Dutch famine you

know the the Dutch weren't able to get enough food in and then you see the epigenetics because you see um across time that the generations several Generations on are still affected by that that uh insufficient food uh back way back then so it's just another example I had okay I'll let you answer now have we covered everything that we wanted to cover do you think I think I think mostly yeah I think we covered an awful lot of ground uh yeah we didn't talk too much about you know satellite Cs and stuff but I feel

like that's a that's a whole other podcast I sort of think and so and what when Chris fry comes on you should ask him because he would be the perfect guy to chat about that with so I can pass that one off to to Chris all right now we did have one you had uh because I like to ask about effective age effect sex differences and things you you did have one I think effects of age on some of this or uh effects of age well as far as muscle memory I mean I know that

there was a study that was done where they they tried to look at this muscle memory idea in young versus age and there was a very small sample size um but they had folks train and retrain young and old and found that at least when you're old older is that the proper thing to say uh if you're if you'reall a person of an older age umse as a person who studies know more about the terminology but it's hard things change all the time as you know but yeah a person that that's older an age uh

would still have the ability to well get adaptations from the training initially but also have a muscle memory effect and it seems like whether you're younger or old or older there's still this like sort of Amplified response to the retraining and so in that sense um it seems like it could be you know a conserved thing across the lifespan but again it's like going back to the question of when the initial training was and then how long you waited was it you know two months or 20 years like these are all very very open-ended questions

we may not even know the answer I guess no one's looked at sex differences so what what did you have both sexes of my saw because again you get a double everything but um or did you have so for most of the studies for our exercise training D training stuff we use females because they tend to run better and run more they tend to be more consistent with they're running and so it's more of a practical consider consideration the females just take to it better and perform better for the the epigenetic studies I'm talking about

though at least the one where we looked at DNA methylation and the myonuclei and isolated the myonuclei and things like that we used male mice because I used all my female mice for other studies and so um so I was left with the males well we're gonna run it with the males and we did and they still ran they ran less than the females but as far as like have we looked at sex differences between them no we haven't um to be determined okay great right well this has been great but while I've got you

I can't help noticing you you had in your CB and things some of these uh articles where you sort of lay type articles you've had and I I couldn't help one jumped out at me busting muscle myths paper so just why we've got you because I know we could get you for a whole satellite sale thing as well but I'm interested about this we address common misconcep misconceptions including the go big or go home and and if you don't use it use it you lose it approaches ah okay so if you don't use it don't

use it you lose it I guess you're saying is part of the the muscle memory side yeah but I guess you'd still agree that if you don't I guess you'd still agree that if you don't use it you lose it to some extent but you do you might get it back faster yeah so that was sort of the the message there yeah of course you well if you're a Solus of a mouse maybe you don't lose it I don't know but yeah exact but yeah that paper was you know just something fun that yeah I

get it now I get it now that yep authors there the other ones Dr Jimmy baggley and Dr Andy Galpin they did a really cool study on nature versus nurture where they had like um it was a twin study where they had identical twins one was a lifelong um was a lifelong uh triathlete and the other one was like a truck driver like never exercised at all but they were identical they're like a really interesting study and show like how radically different their fiber type was and like you know the genetic deter fiber type versus

how much you can swing it on exercise and really interesting so yeah you're saying nature versus nurture it makes me think that's was just such a striking example of how powerful exercise is you know the phenotype radically different it's a published study it was published a couple years ago so it's very very cool so and go big or go home I guess um what were you thinking there I guess oh that was uh yeah know kind of the the Stu Phillips uh sort of uh message that you know you don't necessarily have to live time

to put on exactly exactly so these are good because you don't want to be scaring people off like ah you know it's it's it's not worth going to the gym unless I just smash myself every day and whatever which is it's exactly what we don't want people to be thinking because then they just get sore and they give up true yep all right now what I do have is something I sent to you beforehand was uh part of the idea of inside exercise is because we want people to get their information from the experts rather

than from influencers and I like asking people uh more recently is there something you know this is your chance to sort of take on these influences that are sort of pedling misinformation and now I know you said you don't really you know follow influences which is probably wise but um although someone said I'm becoming an influencer and it's like well no I'm not because okay let me let me in case people are wondering about this even if this podcast got to a million views I still wouldn't consider myself an influencer because I'm not giving my

own opinion you know obviously it comes out here and there but I'm not like going off in like a lot of podcasters and just rattling on about stuff that I'm not an expert in I tend to get my information from experts I try and get people to get their information from the experts and I don't like give my own theories at the end or whatever so I'd like to think I'm not an influencer but um what what you know is something that teases you off that um that you you hear bandied around sure yeah like

I I rate I don't really follow influencers on fit the fitness realm per se so um but I will say it makes me just reflect on the question of what is an expert um because I thought about this quite a bit and it's like there's a I think there are certain couple people that I follow you know have interesting content this and that but you know like just because someone can read a research paper and interpret it doesn't make them an expert you know a lot of people they make a whole stick out of you

know uh what's evidence-based we're evidence-based we read the literature this and that and that's wonderful evidence-based is great but um but you know just because you can read a paper and interpret it better than somebody who doesn't read the literature doesn't make them an expert in that you know like I think about what makes anybody on this podcast an experts the fact that they know the field and that involves reading of course um you have to read the papers but the other part of it is being able to identify when a study is appropriate or

good or bad or whether the methods were done correctly because I mean you can have this wonderful seemingly wonderful study that has all these amazing findings but if all the methods were done poorly and you can identify that then the study's not worth very much and so and I think that's a lot of times where an influencer will go astray they'll see a study come out they don't know anything about the authors or the journal or the methods because they've never done the any sort of research themselves and then they say this is the state

of the literature and it's like well that's the state of one study and it was one study that was conducted I'm not so sure that that's a good message you're living and breathing this stuff for like you know 10 years 20 years whatever you can't just read a few papers and that's the thing that gets because literally people will say to me why don't you you know just just take a few days read up in an area and then do a podcast and just talk about the area and it's like well because I'm not won

be an expert oh yeah but you'll know more than 99% of the audience sure but why don't I just interview the expert and I won't name names but there's all these huge podcasters and people that they just I I don't get how they do it so there's one guy in particular you know he's a whatever he is he talks you know sure okay You' got your own area but you can't talk about 20 different areas but these people are just massive massive the devil's in the details like as with anything you know and I I

me and any other person that studies the things I study knows how has a sense of how methods should be conducted and how assay should be done and yeah all these different just so many experimental considerations for anybody that's an expert in an area and we're always thinking about these things and there's no way an influencer could know the things they just can't and so not to Discount what they're trying to do I think it can be a net positive but sometimes it isn't when it's they get things wrong it's problem yeah and they're often

trying to flog supplements as well I can't help myself okay so um that's great now is there anything um else anything well okay because then you'll get into the satellite sales I was going to say is the stuff you're working on that you're excited about but I think uh we want to wrap that up because I think it's clear that you would like to talk about stuff like that now um all right so how about we finish up with some some takeaway messages so you know when you give a give a talk you think oh

two or three things I want people to take away from this some takeaway messages to to wrap up sure um you know uh it's important to consider you know the experimental design of a Mouse versus a human and these different the different things that go into um a human study versus a mouse study and the different consideration It's always important to view what you're listening to or what you're reading within that light um in the context of muscle memory you know um there's evidence to suggest that it could be related to the number of myonuclei

that you gain and have upon retraining but it could also be related to a variety of other factors it could be related to epigenetics or micr rnas or things that we haven't even measured but I think the idea that if you were to detrain and take some time off and then start training again there's a chance that it might come back a little easier the second time and there could be a variety of reasons for why that is and so um and that's kind of the area that we're working on we're interested in and knowing

knowing more about and so I think uh that probably captures the high points of our talk so yeah I don't know and yeah yeah and the evidence is pretty clear that the muscle because I have to admit when I first looked at this area I thought well was that really a thing or not so the evidence even though there hasn't been a whole bunch done you think it's pretty clear because I know you've done mice but but in humans as well that muscle memory is a thing so if you do exercise training especially we know

more about stren you know more about strength training then I don't know six months two years 10 years later you do it again it is likely you will take to it uh quicker and get bigger or or better quicker and it will be in the muscle it's not just the motor learning it's not just the you know what you're doing and I'll say that the motor learning and stuff doesn't contribute it probably does but you know yeah we think that that's probably the case and I mean I don't think that gives you license to okay

I used to lift 175 pounds on the bench I'm just gonna jump right back into that you know like not a good idea you know like you probably want to have some common sense here but you know if you follow an appropriate prescription yeah there's a decent chance that you might you know that muscle might come back a little bit quicker you might get stronger a little faster um but also you know just the idea that yeah you have to take time off it's not a death sentence you know like you can get back into

it and it can still have benefits and maybe they'll even be come back faster that second time potentially and that's great you know and so you know don't give up actually sorry I was just about to finish now I got often do this I either take away messages and I have something else just thinking what about the health benefits you know so we often you know we talk about the hypertrophy and all that but we know that strength training and Jance training both of them improve you know your glucose regulation and and all sorts of

health benefits blood pressure and things like that do we know if they stick around a bit um boy that's a great question I don't know I've been so in the muscle and so in the cell that about the more important things uh that's a good at least with resistance training I I I don't know uh yeah I haven't looked into that that's a good question be interesting to see if they yeah yeah I would think that with the train from like aerobic training some of that would last a little while but I don't know how

long I don't know good question good question GL well and then I guess I mean you are going to lose some of those health benefits but whether they come back quicker as well you know so maybe you get the the drop in your blood pressure and Improvement your glucose tolerance and all that maybe that comes back quicker as well actually yeah so already health health not just muscle but um whole body Health memory or something okay all right well thanks thanks again for coming on so so you're definitely a rising star and um one thing

is you know you think oh maybe they won't know their stuff as much as someone who's been around for 20 30 years so you obviously know your stuff really well and I think I was actually thinking um that you're a good example of how I couldn't just go and and you know to tie in what what we said before I could spend a week two weeks three weeks reading up on this stuff and there's no way I could do what you did right so that's the whole idea you've got to interview the experts okay well

I appreciate opportunity to be here it's a huge very flattering because your podcast has had like juggernauts in the field and it's really cool counted among them now so it's really flattering for me so thank you for the for the honor and uh I hope that this is beneficial to people I'm sure it will be we listen so okay well good on you mate see you see you around bye bye take care yeah bye I hope you enjoyed this podcast please like subscribe pass it on to your friends and colleagues check out the other podcasts

thanks again