#71 - Aging, inactivity, atrophy and exercise with Professor Sue Bodine

Hello and welcome to inside exercise I'm Emeritus Professor Glen McConnell from Victoria University in Australia and I'm also currently a Danish diabetes and endocrine Academy visiting professor at the University of Copenhagen 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 in 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'll bring to you Professor Sue Bodine from the Oklahoma Medical Research Foundation in Oklahoma USA she's

an expert on muscle and in particular what determines muscle size so we know that resistance training increases your muscle size which is hypertrophy and we also know with aging you tend to lose muscle size so muscle atrophy takes place so we talked about How much of the reduction in muscle size with age it's due to the Aging per se and how much is the inactivity he also talked about whether you can slow the rate of muscle size loss so the rate of muscle atrophy by doing resistance training and also whether endurance training can slow the

rate of muscle loss we also discussed whether nutrition can affect the rate of muscle atrophy with age and also talked about the importance of other things Other than just muscle size and strength so for example with age the importance of balance I found it really interesting I think you will too so stick around you'll see in the that I've included timestamps so ideally I'd prefer if you watch the whole podcast to get the full context but if you wanted to skip around a little bit you can on YouTube go down and click on the times

and you can see what we've talked about and it will jump straight to that point and also on uh Other platforms such as Spotify and apple podcasts you will see the times but you can't click on them if you'd like to do me a favor and help get the message out about inside exercise then any sort of subscribing liking leaving comments Etc on YouTube helps with the algorithm suggesting inside exercise to people when they're doing their searches okay so thanks again and enjoy the podcast hi Sue welcome to inside exercise thanks for coming on Thank

you for the invitation Glenn oh my pleasure my pleasure okay so we're going to be talking about um aging inactivity atrophy and exercise but what I like to do at the start is just sort of ask people um how do they get into this sort of exercise research were they like Sports person initially or an exerciser they thought oh I could actually work on that or were you you know were you a a re researcher and then and then moved into exercise how did you do do that um Well so I mean in high school

I was a was an athlete so I went to um UCLA as an undergraduate and was a Kinesiology major so that's sort of how I got introduced to it um Reggie ederton was my ended up being my PhD adviser but I I really I was interested I got very interested in movement and what controls movement and obviously in the Kinesiology major we had classes in exercise physiology and and so that's sort of how I got into it um by accident As far as research I wasn't planning on on going into research when I started as

an undergraduate but really fell in love with it so did you do like a master's with Reggie or I did a master's degree initially yeah so I did a a master's degree um I started off actually as a uh sort of um focusing on biomechanics and then did a study with um in Reggie's group in looking at muscle function and and really enjoyed it and so then I switched Over to him as a as a graduate student and then UCLA at the time didn't have a PhD program in kinesiology and then just as I was

finishing my master they started one and so um I applied to a number of graduate schools but decided to stay at UCLA with Reggie and um and at the time he had a big program project in spinal cord injury and so started studying muscle oh okay and is that how you started looking at um muscle atropy as Well I guess actually I start that's how I got interested in motor units um I started actually studying muscle atrophy when my I moved to my first um academic position was at UC San Diego and I was studying

peripheral nerve injury and so I actually was interested in what happens you know how the nerve regenerates and then makes contact how the axons make contact with muscle and then started looking at the muscle and looking at the effects of denervation And that's sort of how I moved more into muscle atrophy okay initially I was more neural control of movement before that ah okay so like motor control sort of thing yeah right actually I haven't had anyone on talking about that we should do that okay um all right so if we start thinking so I

I guess aging is going to be a big big focus of this if we start thinking about um why do people lose strength with age we just talk about That generally and then we'll sort of get into things yeah well so you know strength is both a neural comp component and then also a muscle component and I think the loss of strength with aging is related probably to two things one is how the nervous system actually activates the muscle and whether it there are issues there and then also the muscle itself getting weaker or the

muscle fibers themselves getting smaller And so you have less muscle and so strength goes down um as you know generally strength decreases is more rapidly than actually muscle size and I think that is related in part to the the neural component of of what produces strength so it's not just how much muscle you have but your ability to activate those muscles okay so that's interesting because it's the same I guess when and we'll talk about this when you're Actually uh doing resistance training you tend to get an increase in your neural so your nerve sort

of activation and you get the increase in muscle size and you know there's talk about the timing and all that sort of thing so then when you start to lose strength it's it's the same sort of thing yeah I mean if you look at most resistance exercise you know training protocols or training strength improves first and then you start seeing increases in Muscle size itself and I think it's because the nervous system when you do a a movement it's not just a single muscle that's being activated to produce that movement and so so the mus

the nervous system learns how to more efficiently activate you know an individual muscle and and multiple muscles to produce that movement and so you see improvements in muscle strength before you see so if we talk about um strength and then when we talk about losses of Strength with aging what what time what time cost are we actually talking about you know when we're saying losses of strength is it 50 onwards is it 30 onwards is 70 onwards and and and it's not necessarily so if we think about know when do you increase your strength and

when do you start losing it and this is without doing white training just just yeah right and I think it's it's highly variable you know and it so it depends On the individual person so how you know what state they are you know what what how active they've been or there other comorbidities but in general the data suggests that you know in middle age around 50 or so we start losing muscle mass and strength um and it accelerates Beyond 60 and and then even further Beyond 80 and so it's like you said it's it may

be gradual in Middle Ag and you may not even notice it and then beyond 60 is usually where in 70 where you see Biging be big decreases in strength and and then you actually see significant muscle atrophy yes so if we could just talk about muscle atrophy can we just talk about what actually starts happening so you know is are you losing you already touched on the size of the fibers but you're actually losing fibers as well and and what about changes if we could just talk a bit about how you have like fast twitch

fibers and slow twitch Fibers and whether that sort of changes with age as well typically you see a loss of muscle fiber size so individual fibers lose their cross-sectional area and so the so there's not a a loss of fibers per se the the with advancing age and the onset of denervation it's thought that now you start losing um actual fibers and so you have a loss of mass because of a decrease in the size of individual fibers but also a loss of muscle fibers but that can be variable So okay but is the thing

I was thinking about was uh where you start to lose fast right and and that the motor unit the actual nerve does it start to sort of jump onto the slow fibers but but you also lose some at the same time is that right right so you have individual motor units and muscle you know individual fibers are interated by motor neurons and a motor neuron inates a certain number of fibers in in a muscle with age and generally so we have we have slow Motor neurons and fast motor neurons slow motor neurons tend to inovate

fewer fibers than the large fast motor neurons which inovate large a greater number of fibers um and so you have slow muscle fibers and you have fast muscle fibers the the fast motor units or the tend to be in any given movement they are the last there's a recruitment order of motor units and so the slow motor units get recruited first and then the fast the large fast motor units get Recruited during very intense High Resistance exercise so with aging what you see you tend to see is these large fast muscle fibers tend to um

you you lose the number you you lose fast fibers or I should say the fiber type composition of a fi of a muscle becomes slower and so it's because these fast muscle fibers are become d derated or those motor units um retract their their axons and then those muscle fibers become Denervated but then they become reinnervated and oftentimes by slow motor units and so they become slow so there's this preferential loss of these large motor units um and so that and it's unknown you know people are still trying to understand why these motor units are

the first to go um or why are you losing these these motor units um I these I tend to think that these motor units are being lost one because they are the LA you know they're the Most res um they're only activated during intense exercise and so with aging if you are if we're doing less intense exercise they may become more inactive and are seeing bigger changes and and that's resulting in the retraction of these these axons to these muscle fibers um but it's still unclear you know why why you're losing these muscles these motor

neurons and why these fibers are becoming denervated and what happens early on is that you start Maybe maybe in middle age you start seeing this denervation and reinnervation process and with advancing age what happens is that the muscle fibers become denervated and then they don't become reinnervated and so if a fiber doesn't become reinnervated then that's when you start seeing fiber loss and it's thought that that process doesn't happen until very late um so maybe that's you know let's say that's beyond 80 or something um that you Actually start seeing loss of muscle fibers now

okay that can change depending on other comorbidities so so well what about um what about if you wait if you do resistance training can you put and you or or sprinting I it's unlikely people are going to be sprinting but if they did you know if you had 75 year old sprinters you know in the Masters games and whatever if people look to see or or you know people that are doing fairly Decent you know as hard as they can resistance training if people look to see if there is any any slurring of the Lost

of fast motor units and nerves there has been some studies that have looked at yeah the fiber type distribution changes now in human studies it's almost all been restricted to the vastest lateralis because that's where the biopsies um whether it's slowing down that process it's not clear but there's Some data to suggest that resistance exercise or even intense endurance in you know um aerobic exercise could maybe stabilize the process and so these in these motor units may not be motor neurons may not be retracting their axons and so you can stabilize the neuromuscular Junction the

connection between the axon and the muscle um or it may prevent it it may stimulate the reinnervation process so so it does it can be beneficial um W than and so there There's thoughts that that exercise you know both potentially aerobic exercise and resistance exercise can help delay this process and and stabilize this the the neuromuscular Junctions that's interesting because You' think in a way it's actually helping you to be more aerobic more endurance if you're getting you know not once you're 85 or whatever and you start losing to Total fibers but if you're switching

from more fast to slow You' Think that would actually help with endurance type exercise when you're like 75 or something but you're saying the urance if you do Hard urance Exercise you may actually slow that conversion or or you may stabilize intense exercise so what you you can see with intense aerobic exercise in the older individuals you can see hypertrophy and it tends to be of the slow muscle fibers which are probably because they're the most highly Recruited um but it I mean aerobic exercise can have benefits to muscle size in in older individuals but

I think it the idea is that it also may slow down this process of of motor neuron loss and so you stabilize these Junctions and so you may not be getting um this denervation reinnervation process or maybe if you do get denervation you're better able to reinnervate um and so um I Okay Al so you're talking about more the the loss of fibers rather than the converting okay so just to summarize make sure because I lost lost lost it there myself I thought you were saying that if you did uh resistance training and maybe High

uh intensity endurance training you might slow the com the the loss of fast motor units so slow the conversion of fast to slow but you're more saying you might slow the loss of fibers that happen later on well both I Mean I'm saying both that yeah either both resistance exercise and aerobic exercise may may do the same thing I mean they may stabilize so you stabilize the junction the the yes the junction between the axon and the muscle so that you don't get the denervation in the first place and then you wouldn't get the fiber

type conversion okay okay or there's some the other it could also maybe you still get some denervation but then you can get reinnervation by other Motor units so that you stab you you prevent this denervation and the loss fibers okay it's still unclear I mean I think um we know I mean you can in order to stabilize these these large fast motor units I mean we know what you do need to do is more intense EXC you need to recruit them and they get recruited with high Intense or intense exercise or exercise that requires a

a higher force a load um and so it's it's necessary to Recruit them to to have an effect on them okay so why don't we talk about the old classic of the the loss of muscle strength and size with aging how much of it is inactivity so I guess we've touched on that but you know how much of it is inac ity and how much of it is aging and and can you totally stop can you prevent it by exercise um I think I mean it's a combination I mean I think it depends on the

Individual um but what we do know is that that really even Elite athletes long-term athletes start losing muscle strength and and muscle size with age so there is an aging process um that we haven't been able to completely stop we've been able to delay it um but so there's there's probably depending on the individual I mean I think inactivity is playing a role and especially inactivity of these large Motor units these we're not doing as much intense exercise and so certain muscle fibers are are seeing much more in activity than other muscle fibers so I

I think I personally think that inactivity is part of it um it it's not the only um mechanism underlying the aging process there's probably many more it's multifactorial so so if we're talking about um if example if you had and I know it must be hard to control but if You had had an older person doing the same resistance training as a younger person which is would obviously not be the maximum for the younger person do you get the same adaptations or is there is this concept of anabolic resistance um did you want to just

talk about that a little bit yeah I mean there seems the data suggests that there is this with aging this resistance to to resistance ex yeah this attenuated response to resistance exercise and I think it does Depend on age um so some of the Studies have shown you you know that that there seems to like a 60y old can respond as you get to 70 year old or 80-year-old that there's less of a response or that it's harder the adaptation is is is diminished um so there there does seem to be something going on with

aging that's preventing this um the adaptation to this this loading response to to induce also Hypertrophy okay and if we if if we think about um what's actually going on there I know quite often people think about hormones so you know as you get older um you you have lower testosterone lower growth hormone do you want to just talk about that a little bit um whether that's the case or not if that's yeah I mean I I P I don't think the data I think hormones are obviously very important during adol lessons and during puberty

to promote Growth um in the adult I don't think that testosterone or growth hormone per se are are the primary factors regulating muscle size I mean obviously if somebody has really if a male has very low testosterone um that could be inducing some atrophy and weakness and supplementing them back to physiological levels is beneficial um but super phys super physiological testosterone in clinical trials doesn't seem to have Done been able to prevent age related muscle loss um or promote you know promote growth um so I think they become hormones seem to be less important with

age as far as maintaining muscle mass um you know the the reasons for the atten uated response to to loading with age I I think we still don't quite understand it I mean some have suggested that in response to resistance exercise you get this increase in protein synthesis and that with in older Individuals that this increase in synthesis seems to be attenuated um that may or may there's data on both ends saying it may happen or it may not um the other process that we've been looking at um with my my colleague Ben Miller are

that you know you may activate protein synthesis but then something in the muscle the ability to assemble those proteins correctly into new contractile Apparatus may be impaired somehow so even though you're synthesizing proteins you're not able to put them together correctly to get functional muscle muscle and so something in the muscle that that's that this this protein turnover and assembly process is impaired with aging and that we need to figure out how to improve that um in order to get better response yeah that's very interesting so some people would know I already had Benjamin Miller

on and and yeah he talked about he's got some data I think it's a little bit cont you know some people were as you said you know not too sure people aren't too sure what's going on but he actually said there was some evidence that that with aging you may even have higher protein synthesis rates to sort of compensate right well and in animal models we I mean with in with age you actually see resting protein synthesis Is actually higher in in as you get a as you get older um and and even in response

to uh when we do we do have models of disuse and then we allow the animals to to re to reload or to to have full weight bearing the their protein synthes their response as far as protein synthesis is better the old animals have a better response than the young animals so the idea that protein synthesis is somehow the ability to activate protein synthesis is impaired we're not seeing That um suggesting that it's not just a a matter of making the proteins it's it's much more complicated in how those proteins are then put together you

know are they when they're made are they are they folded properly um are they assembled properly um with other proteins to form you know a contractile apparatus so is it also possibly because I guess I was thinking that have higher protein synthesis and maybe higher breakdown but you're saying it's it's More likely maybe it's they're not been assembled properly or something like that or it might be higher breakdown as well yeah I mean we've I mean some people have suggested that the with you know with the muscle loss with aging is because it's all about

increased protein breakdown and and there's actually some data to suggest that certain types of breakdown May in fact be impaired um and so proteins may not be they're not being turned over Properly and and degraded and so they actually accumulating in muscle and and that's causing these Aggregates or causing a problem so protein degradation per se doesn't I mean in some of our animal models and even in humans doesn't seem to be going up as much as high as people say suggest it is so it's much more I think it the the problem is much

more complicated than to say it's much more complex than to say okay protein Sy synthesis is down and protein Degradation is up um it's not that simple and it may be that certain proteins may have a higher synthesis and some may have a higher breakdown but overall it's not like it's you know it's all one or the other so I I think the the field needs to start looking at more individual proteins and what's happening with those individual proteins and just you know looking at protein synthesis that's true because people and it's also easier to

measure Protein synthesis than breakdown as well isn't it so right people often do the overall protein synthesis rate and you're saying some proteins might be up some might be down okay so we just go to a um Twitter question here from Mark how long time periods of physical activity do you see increased health risk so he's saying how long uh do you think you need uh if you're physically inactive before you sort of see health health risks and um What degree of exercise can compensate for that so he's saying if you've got busy work period

pregnancy maternally leave to whatever can you do like one session a week so you know just say if you're normally active and then you become Physically Active is one session or week enough do you need to do more than that I guess it depends what you're doing right I yeah the exercise prescription is not so simple um I mean when we we talk about inactivity and This you know acute atrophy in response to inactivity it's usually something really severe like you know you go into bed rest for two weeks you know or or you're you're

immobilized your limb is immobilized you tear your ACL and you're immobilized for for two weeks you see this rapid um inactivity um or rapid muscle loss aging process is the loss of muscle mass as a function of aging and inactivity is is much more prolonged so yeah I mean if You um and and the other thing we know is that to maintain muscle mass with respect to resistance exercise it doesn't take a lot so I mean 30 minutes of int you know resistance exercise three days a week is enough to you know maintain or build

muscle mass so I think you know even just walking um if it depends on you know what your Baseline is where you what kind of exercise you were doing before um you know so if you were Lifting weights and if you doing resistance exercise a lot um or running a lot and then all of a sudden for two weeks you do nothing you don't you know yes you're going to lose some of your performance capacity um but you can you know it's you can definitely recover it um so I I think it's it's none of

us are you know under the scenarios that this that Mark described you're not totally inactive you're still walking around you're still Doing some activities um it's not like you're you're you know confined to bed and and not not doing any kind of resistance exercise yeah I'm glad you actually brought up those sort of models because I I sometimes um wonder about so you know if they're looking at muscle atrophy as you say quite often they'll do a study where you've got your arm in a cast or or bed rest which is pretty extreme I bed

rest in particular is Pretty extreme often they have head down and and you can't even get out of the bed to go the bathroom and all that and you sort of Wonder um you know how relevant that is to to what you know obviously to aging it's not particularly relevant or are the same sort of mechanisms going on but just faster you know yeah yeah I mean it's it's interesting what you see in response to in a in a otherwise healthy individual with Inactivity um is actually slightly different than what you see with aging and

so um as far as what types of fibers atrophy and what muscles so like with inactivity um bed rest um we do you know cast immobilization like the Solus will will which is a predominantly slow muscle will atrophy rapidly with aging the Solus is actually one of the muscles that's more resistant to age related mus post it's postural muscle um and so you like we just talked About we see these large fast mod muscle fibers aftering first so it's it there's there's some interesting differences between like aging and then when you have these disuse acute

disuse models um you know even when you look at astronauts who' have gone into space and the type of atrophy they see is more like inactivity or disuse um so it's it's it's it's it's their differences and and I think and also I mean the Aging the muscle loss Due to aging is a much more much slower process now it can be accelerated by various diseases like diabetes or or you know a very sedentary lifestyle um but yeah yeah I want to clarify that um I'm not saying that um cast or bed rest or whatever

not good good models they're obviously a good model if you're looking at space you know what happens in space and things like that but I guess sometimes when people are doing Experiments you want to have something you know that you can see quickly rather than you know like months and years of uh well and I think it gets to one of I mean I've studied different entrophy models and aging being on the one spectrum that these models you mean tell us different things you know and that atrophy isn't a single process um but you know

immobilization muscle atrophy due to Immobilization is happens to a lot of people and is is important and so we want you know try to understand what happens can we prevent that atrophy or can we accelerate the recovery um in response to that atrophy and in the Aging context it becomes important too because if you have a period of acute immobilization in an older individual and that person now has this rapid atrophy if they can't recover that now you know puts them at Risk for you know for falling or other things so you want it accelerates

their age related muscle loss and and so now that becomes an important problem you know to be able to build up to to build back that muscle after an acute B of about of um Acy yes of course so bed rest isn't just a good a good model for space it's a good it's a good model for bed rest so yeah if you get those people or you're injured and you're actually in bed then yeah so I know I've seen the Data which you're touching on that if you look at like muscle strength losses or

muscle mass losses of goes down sort of L maybe line linearly is but then if you're you know if you get sick you know then you then it drops and you don't necessarily get back you know you've really got to get and I guess your average person that's just aging normally and is not doing a whole bunch of exercise they have that that drop um when they've just spent a few weeks in Bed or whatever sick and they they don't go back again do they they've got you you actually yeah no many of them don't

fully recover back to their previous Baseline which may have been lower um and so that just you know accelerates their their decline or or makes them Less Mobile um which then leads to this whole you know spiral of inactivity and accelerated muscle loss loss of strength in muscle so is it fair To say then that you know we want people to be doing um you know resistance training endurance training the whole gamut but it's especially important after you've had a period of bed bed rest or you've been inactive that yes if you've had a something

an acute bout of in you know that's acute bout of disuse that's caused you to to have muscle atrophy you definitely need you know weight uh resistance exercise and and and and Rehabilitation and I think that's where many people don't get the rehabilit the rehab that they need and and the intense they they don't get the intense rehab and so you know they may just get mobile and can walk around but to really build back that strength they need some intense resistance exercise and and I think in many cases that's lacking in our in our

health care System yeah I could imagine I could imagine that's the case because if you broke your leg or Something it's it's it's like that you'd be in the hospital system and and then you might have some re you know physiotherapist or physical therapist I think you call them over there um you know telling you to to do but even then they might just be you know if it's your knee or something they might just be working on the knee but not really working on your overall muscle mass and loss of inur you know of

aric you know in a in a young Healthy individual you know recovery I know I I tore my ACL and was immobilized I mean it took in a couple weeks I lost significant muscle mass and it took months to recover that and so that's in in somebody that's healthy and doing rehab versus you know your average person and so I mean it can it can take a significant amount of time and whether people you know stay do do the exercises they need to do And I guess they wouldn't you don't always think about you know

you think about working on that leg that you've damaged but you're not thinking about the fact you've been in Mobile you know more generally as well and and also if you've been in bed with coid or the flu or you know whatever it is you've had some illness it's not usually front of mind you know for the person or the doctor to say okay now you're back up and that you know up it's very important To go and exercise I don't think that's yeah doesn't seem like often times yeah if you had some severe illness

and you've lost a lot of weight a significant part of that weight loss is muscle mass and we don't don't think about it you know we think of weight loss as fat mass and so you've lost muscle and so we know you know you have to rebuild that strength and rebuild that muscle mass too and and we don't always think about that hey can I Ask you a different a different sort of question so you know like distance Runners and cyclist so you know FR cycle they have like very weedy upper bodies right and which

is actually a good thing because you don't want to be carrying extra weight if you're a serious Runner or cyclist do do we know if that atrophy because you know we've been sort of talking about inactivity and aging where you're sort of at you you're losing muscle kind of equally everywhere sort Of thing you know relatively um do we know what's going on there is it just because they're not using it that they're losing it or is there some sort of redistribution going on do you know I suspect that it's that it's because they're just

not using it they're not I mean they're they're not doing any kind of strength exercises and they're trying to probably keep their weight down too and so it's Advantage for performance under in that task to have a have less Muscle mass upper body so exactly but there's no sort of because you know how you get increases in cortisol and reduces and you know you can get changes systematically systemically that so cortisol can break down protein if you if you're like training cycling hard running hard you might have an increase in cortisol decrease in testosterone ratio

and things like that for a while there you know I think there was some thought that might be playing a role in Reducing the size of muscle that you're not using but but I guess it goes back to what you said earlier that that I guess once you're you know par adolesence and a young adult it's not really hormones that are probably playing a role in that so yeah unless I mean even I I doubt it's the cortisol that's that's inducing the that they're getting selective muscle atrophy I I suspect it's just it's it's um

specificity of Exercise you know exactly makes more sense I know cyclists have problems with osteoporosis and Bone strength um yeah it's funny actually I think that was a prevailing view or it was my idea at one stage I was thinking how so when you're exercising you've got local growth factors and local activation of protein synthesis and all this sort of stuff and then the ones you're not using are probably like getting chewed up because of the high Because I know we were doing an overtraining study and everything was quartis all testosterone balance and all that

but I think that's all gone out the window so I'm happy to to go with you on that one um so uh Mark has another question here if you don't mind on Twitter what is the minimal dose well I guess we've talked about that but the he said minimal dose of exercise resistance SL endurance that pre preserves healthy Aging uh the one there I guess we've touched on that if um but you you did mention earlier that endurance even in older people you wouldn't necessarily think of that but endurance can actually help maintain your your

muscle uh fiber size yeah did you want to just talk about that a little bit yeah I mean there there are some studies and I think it's I mean it's the intensity of the endurance exercise but if you do you know intense so above 70% V2 Max um you Can see um improvements in muscle size in fiber size it's predominantly the slow fibers which I think are it's probably because they are the most heavily activated but you you can have you can see um improvements in in um or see fiber hypertrophy with endurance exercise if

it's that's interesting at a higher intensity and I and I think it's probably because especially in you don't see it in a younger individual per se older individual and I think it's just Because you're seeing this significant increase in activity you're recruiting these fibers that you haven't been recruiting and so you're you're seeing this this increased both activation and load on these on these muscle fibers and they're responding by increasing their size um yes so like you're saying there so it makes sense if you're an endurance athlete young young where you haven't got this atrophy

of fibers that are Getting smaller they they don't tend to change size but if you're older and your fibers are getting smaller which a normal process of Aging you can slow that or prevent that by actually activating those fibers and also I mean most of these studies in humans have tended the you know the subject are selected to be sedentary so you're taking a you know relatively sedentary individual and you're increasing their exercise Significantly um and so they're seeing a positive effect now if you took a healthy active older person it may take more to

get them to hypertrophy um but I think this is this you know people want what is the minimum dose I I don't know that we know that and I think it it also depends on you know what your starting point is so you relatively active you know healthy you know nutrition you're not severely overweight you you've generally been Active that you may have a different prescription than somebody else you know um a very sedentary individual um you know um maybe quite different the other thing is I was just at the gym myself and I I

always think if you just say to someone if you just say I going to the uh gym and doing resistance exercise for 30 minutes you know a day that it depends what you actually do at the gym I spend most of my time thinking No I won't go on that machine because there a person sitting there checking their phone so I'll go there and do that exercise and I'll come back later and see if theyve so you know this it depends what you're actually doing at the gym you know are you actually kicking butt and

working out hard or you're actually just doing a set checking your phone looking in the mirror it's it's it's you know like and I remember I remember I saw a woman once At the gym and she was on a recumbent bike and she was pedling like I can't people on YouTube will see this but people like it was must have been about you know 10 reps 10 revolutions per minute and just like really wasn't like it was because it was so hard it was just slow and just watching the television and I can imagine her

then saying oh I'd be next I'd be been going to the gym every every day and I haven't lost weight or but you're not actually Doing anything you're not you don't just go to the gym and it magically happens you've got to actually work out right yeah there is a intensity does matter um I always like the you know the the the bikes or even the the ecliptical and you know it has the different intens or different categories you like the fat burning and people pick that one which happens to be the lowest intensity exercise

oh but you know I've got I've got it on that's true that's true all Right now this is one you may again from Twitter just I just I encourage people to send questions how to ask so Adam should athletes be concerned about being mostly sedentary for the rest of the day if they run or cycle for two hours of the day so that's the old thing about you know I so I used to ride to work back so it was about I don't know 22 kilometers each way I don't know that's 14 kilometers you know

hard I'd used to be running late And then ride home hard because I'm running late picking up the kids or something but then I'll be sitting around all day so the old chest I know this isn't your main area of research but um any thoughts on that I mean I would say no you shouldn't you know be worried and and the fact that you're doing that plus I think people forget about that a lot of the adaptations I mean after you stop exercising you're still you know your resting metabolic Rate everything is still high and

there's a lot is going on during those recovery periods um and so and you need those recovery periods and you know you're not being totally during those periods if if if you're exercising two hours four hours a day it's not like you're totally inactive during those other periods of time so um I would not be worried I think he was saying two hour day yeah four I think yeah he wouldn't Be too old um now the other thing I just wanted to think about sort of with practicalities so if you've got an older parent or

grandparent who's who's been inactive um you know what do you suggest because you know it's tempting to say oh you know Grandma go to the gym three days a week and do weights and and then the other three days do endurance and you know that might be the the best case scenario right but how do you think what what would you actually be prioritizing You know because you mentioned walking earlier um and you mentioned false prevention as well know these are things know anyway what would you suggest if someone said that I mean I I

think with getting out and just walking you know and even if you have a neighborhood that has some hills and stuff you know you're going to get some resistance exercise and and increased intensity if you can walk up the hills um so if you know if it's not Just flat but just getting out and exercising I think like you said I mean a lot of the other thing that goes with aging that we don't think about so much is balance um and you know there are exercises that you can do at home for balance you

can even you don't have to you know even little things like resistance bands or other things that you can get some you know resistance exercise with if for your grandma or Even some free weights and even if they're small um to you know to get your elderly parents to to be doing some resistance exercise um but you know a lot of it is is just just get up and move um exactly and you know not sitting around so like trying to walk more often and make it you know part of the normal life um and

and you know rather than sort of suggesting go to the gym or whatever have have like you said bad Bands to have it home or or some little barbells or something yeah right do you know what age Care Centers do you know if how well they're doing with that I mean there are you know there I don't know other country like you know there's more active um active living um residences that have a lot of you know cours classes Fitness classes for elderly there you know some communities do a really good job of having Community

Fitness um and Programs but I I think it's probably depend you know it's highly variable across communities um some do better jobs than others um now I saw you had a paper effects of diet we haven't really talked much on diet I guess effect of diet composition and chronic obesity on muscle growth and function and may me think um you know it's quite often there people are interested in protein protein supplements and things if you're Inactive and aging you know and then getting older do things like any any protein supplements anything you eat really make

any difference or do you need to be doing I I know I know we we'd bit fur than to be doing exercise but is there any evidence at all that anything you eat can like slow the rate of loss of muscle well well good question um I mean if chronic inflammation is thought to be you know contributing to age related Muscle loss or other aging factors um you know if diet can influence you know inflammation obviously that would be that that would be positive to um or I mean obviously insulin resistance diabetes can negatively impact

so maintaining you know proper glucose homeostasis all of these are important protein per se I mean I think the data I think you want to have adquate levels of protein and with aging Whether you know if you're if you're not getting enough protein in your diet I think it's important but I I don't think the data had you know the protein supplementation above and beyond the daily re you know what's recommended I don't think is have been shown to have any positive effect um so you know I think you need to be doing some kind

of resistance exercise coupled with you know having adequate protein adequate protein to have yeah so If you don't have adequate obviously um getting supplement or you know increase most I guess most do right so which is what you're saying um so yeah I've had Stu Phillips on and he he made it pretty clear that um you know you didn't have to be sort of worrying as much as people tend to worry about with protein but I guess there is some evidence is there that that um as people age they maybe need more and don't get

as much or I'm not sure I don't know yeah I think There's some evidence that people are not getting adequate protein um you know and some some with aging you know their their um what's the word I'm looking for they're not anorexic but they're they're the amount of food they're eating is lower not eating it there's not eating as much and they may not be eating as much protein as they need um so I think you know making sure that people are getting you know the the recommended Amount of protein is important yeah but for

most Americans exactly you know protein intake is not a major problem exactly well that's the thing I was yeah because people tend to think oh I'm going to put on I'm going to go to the gym I want to put on muscle I need to have all this extra protein when they're probably getting enough already oh now I'm missing now I'm losing muscle as I'm getting older oh what's Muscle made of Protein okay I need more protein but it's really 99% of 95% of what is go go and actually do the exercise yeah well and

for me it's just like yeah that I mean just eating protein that protein doesn't automatically go to your muscle and build muscle I mean muscle muscle needs a stimulus to add protein I mean to build and so that has that's resistance you know having to to exercise against the load that it can't lift and so and so yeah to build that Muscle you need adequate protein but just taking more protein the muscle is not going to the body is not going to deposited in muscle as as as increased fiber size it's going to deposit it

as fat unfortunately exactly because you need the you need a signal you need the muscle needs to go oh I'm going to convert some DNA to mes RNA to transfer RNA go out and get the amino acids I need and then make the protein you know just eat protein and the muscle gets Bigger that would be nice would be nice actually I just saw I actually copied and pasted one here I saw Van Loon Luke vanloon who's actually gonna come on the podcast he found resistance exercise training in older adults uh he compared 65 to

75 year olds with over 85 and he actually got similar increases which is interesting prong resistance exercise training increased muscle mass strength and physical performance in the Aging Population with no difference between 65 to 75 years and 85 plus years Ian had look at that I don't know if you saw that not but that's yeah I I haven't seen that paper I mean I know you know the Scott trappy group years ago showed how to study in women and he they showed significant differences between between 60 year olds and 80 year olds so I don't

and you know so I don't know um what the exercise was how long it was you know um the other thing is I I think when we're Comparing some of these studies too is what's the underlying um uh health of status of these individuals you know how sedentary have they been um exactly see to see the paper yeah I assume they train the same which you'd have to assume that but maybe they because I was thinking you'd have to train I would have thought you'd have to train the older people harder to get the same

adaptations but um guess We're just speculating did you I don't know if they're mailing yeah I think there may be some sex differences too but I don't sex was what they was mixed yeah you've touched on this a couple of times but I haven't really brought it together do you want to just talk a little bit about disease and how can affect muscle mass so you know you spoke about people with diabetes Etc do you want to just flesh that out a little bit well I think so you know maintaining Muscle mass I mean and

especially with age is or many things can induce muscle atrophy and so we know just you know that inflammation we we talked about disuse so inactivity um both you know decreased resistance extra Contra contractions against load or just in decreased contractions in and of itself um nerve injury um which results in disuse but you know inflammation can induce um Can can induce muscle atrophy you know high High cyto loads and so [Music] um disease processing so you know with aging if you have have other underlying disease processes cardiovascular disease um can result in in loss

of muscle mass diabetes so all of these things you know renal failure liver failure so all of these can complicate or accelerate loss of muscle mass you know um as even when added on to just aging process so I think when we look at the you know Population and people ask you know about they want a prescription or something for exercise or you know to what is the what's the percent loss of muscle mass with age I mean it's highly variable and I think we need to understand the you know the underlying other underlying comorbidities

or health status of these individuals um because many often many studies also you know they they want relatively healthy sedentary individuals and they may respond really well but Somebody that's not as healthier or on a number of different medications may may not respond as well as a a generally healthy individual so and even if you have a diseased a population with a disease so like people with type two diabetes often you want them to to not be on medications or so that's so even when you're studying someone that's got a disease you're not actually looking

at the average person that has that disease anyway so we've Done studies looking at you know we've shown that glucose uptakes dur exercise is normal when people of type two diabetes but then you think well they were just diet controlled you know is that the case if they're on you know metform and or or they had high blood pressure as well which is you know a co-founder um now I know you've done a lot of and this is where I I'll remind people that we have time stamps so you can look at the if you're

on YouTube you Can look at the bottom you can click on the times and then if you're on the other platforms you can see the times I know you've done a lot of work on mechanisms but if people don't want to hear about mechanisms they can skip this part um but I think it wouldn't be nice if you because I mean that's been a major thing so did you want to talk a little bit about uh What mechanisms you think are playing a role in muscle atropy um yeah um so I started looking At mechanisms

probably little 20 about 20 years ago um trying to understand what's inducing muscle atrophy I think the what I've learned is that it's not simple it's complex and and that what the underlying mechanisms May differ depending on what the trigger is um so and and so like with use atrophy I mean we know that in the models we've used with a cute atrophy I mean a decrease in protein synthesis can definitely contribute to muscle Atrophy um usually in many especially if it's a a rapid atrophy It's a combination of changes in protein synthesis but also

changes in protein degradation so activation of processes that increase the turnover of specific proteins um and in you know in Al the critical proteins for turnover the contractile proteins so breakdown of the myofilaments and um is going to lead to muscle atrophy so we've been you know so you you have a a Combination of effects of you know certain proteins these proteins are being their synthesis is being reduced and and their breakdown is being elevated um it's not always that that simple um and you can have under atrophying conditions you can have some proteins where

their synthesis is increasing and and these may be proteins that are supporting elevated protein degradation so you don't want those proteins being Synthesized um and then you have proteins that are being accelerated as far as their breakdown and so we've been studying you know trying to understand what some of these mechanisms are and and actually in in the course of trying to understand synthesis we started looking at mtor um and you know determined that you know activating mtor with resistance exercise was important and if you suppress mtor Activation you get you know less less hypertrophy

and that oftentimes with atrophy um mtor can be suppressed but there's probably other Pathways contributing to synthesis that are being suppressed other than just um Amor but mtor has been the one that's gotten the most attention and then on the degradation side we've been looking a lot at activation of um so we identified two enzymes that are called E3 liases um That are part of the ubiquitum proteome pathway and and so these E3 ligases add ubiquit in to protein and and and usually add ubiquit in in in Chains to specific amino acids and that often

and that usually targets these proteins for degradation but unfortunately it's not quite that simple ubiquination doesn't always Target proteins to to degr um for degradation um but we've started un uncovering different um proteins that get get Elevated um and specifically these E3 liases that get elevated during atrophy um that seem to be associated with the atrophy process um so the idea is if you could suppress the UPR regulation of these proteins or these enzymes could you suppress atrophy and in some cases we can if we if we um if we prevent these proteins from becoming

upregulated we can atten the atrophy process um unfortunately it hasn't been easy to Target these proteins for um to Suppress them so I mean that's been a a qu a problem um you know the okay it hasn't it the you know trying to prevent muscle atrophy hasn't been easy has it's has has not been an easy target as far as you know what's the best way to do it it so unfortunately I wonder if you're fighting sort of biology in a way because because as you age um and you're not using your muscles then you

know it's it makes sense sorry if if you're Not if you're aging and you're not exercising then it makes sense why would you keep this muscle if you're not using it sort of thing so you know you're trying to if you fight if you're trying to come up with an agent to sort of you know reduce the breakdown of muscle the muscle might just be going well why would I be doing that know like if you're not using it you lose it right and that's I mean it with even these acute androphy you know when

you have Disuse is you know a significant inactivity I always I I think of muscle as a very smart tissue you know maintaining muscle mass is very expensive and so if you aren't using it why maintain it and so the the logical thing to do is get rid of it and and just not and then not you know break it down and and not recover it um or not rebuild it and so you know under normal circumstances these proteins get turned over all the time but you rebuild you Know you replace them because you're you're

you need that muscle but what's interesting is is muscle under most atrophy conditions as long as the nerve is still intact the muscle will decrease in size but it reaches a nater and it doesn't go below that and I've always been interested in you know somehow it knows you know stay stay at a certain size maybe so that you can move but um it doesn't keep atrophying it it goes down to a specific set point unless There if there's no nerve intact then it will continue to atrophy I was interested you said that so mtor

which is known to be stimulating protein synthesis you said that goes down with inactivity I can't remember if you said inactivity or aging but I but you also said earlier that in in Ben Benjamin Miller that protein synthesis if anything goes up with aging so I was wondering why am talking what's interesting is mtor is in these models Of Aging mtor is chronically active and so um so chronic activation of mtor may be it's suggested that chronic activation of mtor is leading to this increased protein synthesis that we see with aging um why why mtor

is chronically or how it's being chronically activated it's not clear um and in a normal muscle what we know is so during like puberty during rapid muscle growth mtor is high once you sort of reach a you know a a stable muscle Mass mtor resting muscle resting amtor levels actually decrease and they're relatively low in a healthy muscle that's not being you know loaded and then with resistance exercise it gets acutely activated but then it comes back down so it appears that acute activation of mtor is important for building muscle but you don't chronic chronic

levels of mtor seem to are NE are are not beneficial and in models that have elevated mtor activity in muscle it Leads to Pro um change Es at the neuromuscular Junction and myopathies and so you want M you don't want mtor to be chronically active um and so that's sort of the the this this ties in with so many other things so you know like insulin's chronically elevated when you're insulin resistant and then you know now it's it sounds like you're saying you know when you're anabolic resistance your mtor which stimulates protein synthesis is Chronically

elevated and how like if something's chronically elevated it's not always the same as it it's acutely so the same with reactive oxin species so I had Carlos I always forget his surname but yeah if you have with exercise you get increase in reactive oxygen species you know transiently and then it goes down again but if you got chronically elevated reactive oxygen species that's a bad thing and even even I guess talking about we were talking About cortisol I mean with intense exercise cortisol is activated but it's not doesn't stay up I mean chronic high levels

of glucocorticoids cause muscle atrophy but activation of cortisol during exercise doesn't generally induce atrophy and so like you said yeah it's it's how it's being activated and that it's not staying you know chronically elevated yeah and it fits with what you saying about inflammation as well because there's some it still does my Head head in a little bit but there's some evidence that you know acute exercise can be cause inflammation in muscle but but that but then you've got chronic inflammation you're saying would cause um cause atopy so it's it's different yeah no and yeah

it's you know it's all about the timing and and and the ACT you know the the the level of activation um that's right is it how high does it go is it and then and sometimes also what other things are Activated at the same time so it's usually not you know with with with chronic systemic inflammation it's not a single um cyto kind that's elevated it's multiple ones and so how they're interacting right all right um I think we've covered a lot of ground here is there is there anything you'd like to to bring out

before I start doing my wrapping up I think we did yeah I think we've Covered a number of topics all right um one thing I like to do I've started doing is you know the the main reason I start inside exercise is I want people to get their information from experts rather than influencers and I just something I've started adding the last couple times is there anything that's kind of out there that you find particularly annoying in your field that people are you know are talking about or thinking that that you you think doesn't Really

add up scientifically well I think one of the things I see and I I see it it's even being taught sometimes in exercise physiology courses in to to undergraduates is this idea that to build muscle you have to break it down that you know muscle injury you have to induce muscle injury in order to to build muscle and I I would say that under most circumstances I don't think that's the case that you you're when you Do resistance exercise you're not inducing this you know severe um muscle injury you know degrad you know and the

the muscle fibers are not degrading there there may be some slight micro injuries there and and but the muscle's remodeling and and yes you have to in order to remodel muscle you have to activate protein degradation and so protein degradation is not always a bad thing you need a balance between degradation and synthesis to build Muscle but that under most you know it's not like we're regenerating muscle you know when we're building muscle in response to um to resistance exercise um I guess that's one um I think there's you know for a long time um

this idea that people talk about we've talked about muscle strength we've talked about muscle we didn't get into it very much is muscle quality um you know um strength per muscle muscle size or cross-sectional area and we talk about Decrease in quality and I think or people talk about specific tension and in humans it's hard to measure specific tension because you can't you need a you need a absolute precise measurement of force and you need a precise measurement of crosssectional area and you can't get that in humans and so you know it's voluntary strength it's

voluntary um strength and maximum voluntary contraction maximum volunt contraction So it depends on the person's motivation you're also usually you're measuring strength about a joint so you're it's not a single muscle we're talking about you know when we do a when we're measuring strength at the knee it's multiple muscles and then how do you accurately measure the mass that's producing that strength and so you know it's a very relative term um but you know people make are often you know I I I guess I quibble with the use Of the word specific tension when when

doing that measurement it's it's sort of like it's normalized Force um and it gives you a idea of you know is is the quality of the muscle going down as far as the ability of the the inference is that somehow those muscle fibers can't produce this you know are somehow not producing their maximum Force but there's many things that could be going into that so I okay so just to clarify for people this Specific attention you'd be saying how much force and Newtons what it per gram of muscle and you're saying that's very hard to

determine in humans because it's complicated yeah or anytime in Vivo even you know when you're I'm very glad you brought that up because I actually had that in my I don't know if you saw the dot points I sent you a potential discussion points I did have in their strength per unit muscle but what I decided was I was wasn't going to ask You that because I felt like we'd sort of covered that when you said that with a with age because you said you tend to get more slow fibers than fast so I thought

well based on that you would expect to have less Force per unit muscle anyway wouldn't you well so that gets yeah this idea that slow fibers are inherently weaker than fast fibers and I think that when you the that gets that specific tension and when it's been measured you know in single fibers or Even at the crossbridge level the difference between slow and fast fibers from the data I've seen is not significant it's highly they're very close and it can't explain the big differences for so actually as part of my dissertation was at trying to

get at this because every the Dogma at the time was that slow motor units were were you know we knew that slow motor units produce less Force than fast motor units and the Dogma was that that was because Slow motor units slow fibers are inherently weaker their specific tension is smaller but the fact is is that there's the force of a slow motor unit is lower than the force of a fast motor unit because the slow motor unit has fewer fibers the the number of fibers inated per motor neuron is smaller so it's a function

of inovation and the number of fibers not the not the inherent ability of slow masas and you Know so you're saying per per muscle fiber you're saying the force is not because I always think of those you know the the twitch the bigger twitches and slower twitches and flatter and all that with the S I thought that was a single cell but are you saying that's a single motor unit well no it depends on what you're I mean you can get a twitch of a single fiber I mean depend you can measure twitch of a

single fiber of a whole muscle I mean you can do you can Measure the twitch of a single motor unit so I mean you have to Define you're saying if you do a single F if you do twitch or or you just Titanic you just do the max there's no difference in force really well no so well if they're the same cross-sectional area yeah a slow fiber and a fast fiber that are the same cross-sectional area area are will prod Force now we're starting because fast fibers are bigger aren't they fast f well that's it

so fast fibers well not All fast oh okay not all do a whole another podcast on this one on fiber types but yeah and in humans actually I mean slow muscle fibers are pretty big in some muscle I mean if you look in the human data depends on the muscle I mean slow fibers can be relatively big especially in the Solus so I I think it depends on the muscle you're looking at but this idea that slow fibers are inherently weaker false I mean there's the data is Variable but most of it shows that if

if there there may be a small difference slow fibers might be slightly weaker you know less Force per cross-sectional area but it's not enough to account for some of these big differences we measure in force so okay well it's interesting when you mentioned cus again I wanted to bring up that point because I thought it was really nice you said with um age if anything you you maintain your Solus um strength better than some other muscles Because they're so slow twitch and they're so important for posture so you know you're using them still but then

if you go into space or you do bed rest I guess because you've taken away that posture then they actually Fe more I think that's really quite interesting yeah they they tend to attribute the the greatest under these unloading conditions great all right so is there anything just um is there anything you're excited about that we haven't Talked about that you're working on at the moment that you want to bring out or kind of covered everything I think we've covered most everything really good all right so what I like to do at the end then

is to have take away messages so what would you like people to take away from this chat um well with respect to aging I mean I think um you can you know aging there is an inherent aging process that that's going to affect all of us but we can Slow it down and I think you know maintaining a healthy lifestyle which means you know being Physically Active um is important and so to stay you know be it walking or whatever um you know you know try to maintain a an active lifestyle and and that I

mean resistance exercise is important and so however you can get that you know be it if you you know if you do belong to a gym and you can go to the gym three times a week and exercise it doesn't take a lot of time Um but you can do it by other means too at home with resistance banss um and and other types of exercise so squats you can do it at home um but and then I guess the other you know with aging the um obviously with fall prevention it's not just strength and

aerobic exercise there's balance and attention to um to that aspect of it so actually before we started I said I often do the takeaway messages then I think of something else so I'm I'm going to do That again thinking if if you've got someone who's never done any resistance training at at all is it correct that you can still H per for your muscles so they've even shown like 90y olds and things is that is that correct so this I believe so yeah I I think you know with the proper loading that you can get

responses yeah it's never too late to start um I would say that but I would also say the earlier you start probably the I Mean that that I I do believe that what we do as young adults has consequences later on and so if you have kids encourage them to be active um and you know I think if you look at you know the rate of loss of males and females I think that the rates tend to be higher faster for men but women hit that threshold sooner because we just have most women have less

muscle mass and so I think it's important um for for women to definitely be doing Resistance exercise actually year now I've got another one I added my notes but we never brought up females why is it they don't hypy as much so if we're talking about you know once you're an adult um it's mainly what's going on on the muscle and it's not so much hormones why is it that females do not hypertrophy as much when they do training do you know I would say I think the data if you're comparing an adult women and

men Doing the same if they're if you're controlling the resistance the loading their percent gain is identical to to men so there's no there's no difference in in the ability of men versus women to hypertrophy um from the data I've seen oh I've got that one wrong then so you mean if they do the same absolute or the same relative yeah um well not they won't have the same AB so percent load yeah you know they're working at their relative percent max I think the data Shows women can hypertrophy now we're talking young adults um

that the response is is identical um well I totally did not know that yeah that's why we got to have these podcasts I'm not expert I don't sit around some podcasters sit around saying what they believe thankfully I don't do that I interview the experts so no I I I think yeah women can and so you know probably in the general population I suspect women are just not Working out at the same level the average person female versus male um but all right well thank you very much for coming on thanks for your time and

uh see you around somewhere hopefully maybe the conference okay thanks see you bye 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