Jacob Goldstein
Jacob Goldstein spent more than a decade as co-host of the Planet Money podcast. He's also the author of the book Money: The True Story of a Made-Up Thing, which the New…
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Kevin Murach is a professor who studies muscle cells at the University of Missouri. Kevin’s problem is this: Can we understand what’s going on in our cells when we lift weights – and can we use that knowledge to help people stay healthier as they age?
In this episode, Kevin explains:
- The technology lets scientists watch individual muscle nuclei during exercise
- The significance of a cancer gene called Myc that is activated after lifting weights
- How Myc may be linked to cellular age reversal
- Why muscle responds less to exercise with age
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Pushkin. What happens to our muscle cells as we get older?
00:14
Speaker 2
Poof.
00:15
Speaker 1
Nothing good. Sounds bad. I'm Jacob Goldstein. This is What's Your Problem? And my guest today is Kevin Murek. Kevin is a professor at the University of Missouri. He studies muscle cells, and his problem is this. Can we understand what's going on in our muscle cells when we do things like lift weights? And can we use that understanding to help people stay healthier as they age? As you may have noticed, this is the second week in a row that I'm interviewing a scientist who studies muscle cells and aging and how exercise can help blunt the problems of aging. And I'm doing these interviews now because I feel like we are at this incredibly exciting moment in the science of fitness and aging. It's been clear for a long time that exercise is really good for us in lots of different ways. But scientists are just now starting to really understand at the cellular level why exercise is so good. Kevin and I discussed this powerful protein called MYC. spelled M-Y-C. Kevin has been studying MYC for a while, and it may be a key part of the reason that lifting weights and doing resistance training can help us stay healthy and maybe even slow the aging process. But to start, Kevin told me why scientists are suddenly learning so much more about what goes on inside ourselves as we exercise.
01:50
Speaker 2
I think we're in a, everybody probably thinks whenever they're working on in science that they're in some sort of renaissance, right? Because whatever, whatever you're doing at the moment is like the most cutting edge, cool thing.
01:59
Speaker 1
Hopefully one hopes so. Yeah.
02:01
Speaker 2
It's good. If you think that it's good, but you know, like, uh, I think the renaissance of, of my age right now is like all this single cell and single nucleus technology that's come on board. And now in the last, really the 10 last 10 years and really probably last six or seven years in muscle. We've gotten into doing things at like a single cell resolution. So like we'll say, okay, here's a single nucleus from a muscle fiber that we're going to analyze. Here's a single stem cell. Here's a single immune cell. We're going to look at all of these individual constituents and what they're expressing on an individual cell and nucleus level. Whereas before we were just getting like kind of a mashed up aggregate snapshot. Now we're able to kind of say, oh, wow, like this particular cell type, this nucleus here is doing this in response to exercise. And what does that mean? It's incredible. Like the technology to me is mind blowing. I'm sure like I think everybody does science in a given moment probably says that about whatever it is they're doing. And they're like the mind is blown by the technology.
03:10
Speaker 1
I know. I mean, I know you have looked at at cell level behavior, gene expression in the context of both. resistance training and exercise in muscle cells, right?
03:19
Speaker 2
Yep.
03:20
Speaker 1
You have found a protein called MYC. M-Y-C. It's pronounced MYC.
03:26
Speaker 2
Sure.
03:27
Speaker 1
And that seems important in the context of resistance training and aging. Tell me about MYC.
03:31
Speaker 2
MYC is what's called an oncoprotein, right? And so, or an oncogene. And it's probably one of the more studied oncogenes out there.
03:40
Speaker 1
Onco, like oncology? Like cancer?
03:42
Speaker 2
Onco, like onc, or onco, like cancer.
03:43
Speaker 1
Yeah, exactly.
03:44
Speaker 2
And the reason why it's called an oncogene is because when it gets dysregulated, so like if it acquires a mutation that turns it on too much, like basically it's usually not on. Usually it's off. It only turns on in response to specific things. But if you mutate that gene, turn it on all the time, that cell turns into a tumor. So you mutate this one gene.
04:06
Speaker 1
Yeah.
04:07
Speaker 2
You get a tumor. Or you get a cancerous cell that can become a tumor.
04:10
Speaker 1
And just as a point of clarity, I called it a protein. You're calling it a gene. I mean, it's basically the gene that expresses the protein. The gene that expresses the protein is Nick. Bingo. So if it's mutated and makes this protein all the time, that's bad.
04:23
Speaker 2
That's bad.
04:24
Speaker 1
You get cancer and you don't want cancer. Okay. And that we knew. That's the kind of what we knew before you came along. So we know it's an oncogene. What else do we know about it? Why were people interested in muscle adaptation?
04:35
Speaker 2
Yes. So basically it had been recognized and also my work had shown that it gets turned on in response to resistance exercise, specifically in the muscle fiber. It has functions in the body like any other gene does. It's just when it gets dysregulated, it has this really negative thing associated with it. So that's what kind of gives it its name.
04:54
Speaker 1
Bad reputation.
04:55
Speaker 2
That's what gives us bad reputation.
04:56
Speaker 1
Sure.
04:56
Speaker 2
But it's just a gene like any other. It does all types of things. It's important for a lot of functions in the body, but only in small amounts. It's tightly regulated like for a reason. It's powerful. Because it's a transcription factor, which means that it's a protein that can go, once it gets made, it can go into the nucleus and then turn on a whole bunch of other genes, right? So that's what a transcription factor does.
05:16
Speaker 1
So just to be clear, what MYC does, it sort of goes back to the DNA and says, whatever, you particular gene, turn on right now. That is what MYC does.
05:26
Speaker 2
Yeah, or you hundreds of genes turn on because we need to do X, Y, or Z, and it's going to require all of us.
05:32
Speaker 1
Yeah, Right. It's never one. It's always so complicated. Yeah, yeah, yeah.
05:36
Speaker 2
It's always so complicated.
05:37
Speaker 1
Does it also turn things off? Yeah, sure.
05:40
Speaker 2
Yeah, it certainly can.
05:41
Speaker 1
So it's a protein that turns other genes on and off to express many other proteins or not express them. Okay, so that's basically what it does.
05:48
Speaker 2
So it goes in the nucleus, it turns on other genes. So when you lift a weight, you go to the gym, the nuclei inside your muscle fibers, and again, there's hundreds to thousands of those in each individual muscle fiber, and you may have like five or 600,000 of those in your vastus lateralis, right? the nuclei inside of those individual muscle fibers will turn this gene on. And that, to me, was really cool because I was like, oh, it's an oncogene. It's turning on. What's it doing? Like, why would you want to turn on an oncogene in response to exercise? But the thing is with really cancer in general, though, like what is cancer really? It's uncontrolled growth. It's a growth program. And so when I go to the gym and lift a weight, I'm turning on growth programs.
06:35
Speaker 1
To grow the muscle cells.
06:36
Speaker 2
To grow the muscle cells. And so you're using, biology uses a lot of the same things for different purposes. And a cancer cell will turn on MYC and proliferate. The muscle fiber doesn't really proliferate. It's not like you're making more muscle fibers. You're just making the existing ones bigger.
06:56
Speaker 1
Right. That's what happens when we lift weights, to be clear. It's not that you get more muscle cells. It's the muscle cells you have, the muscle fibers you have get bigger.
07:03
Speaker 2
Precisely. And the muscle cell seems to be using the same kind of cancer program to make itself bigger. And at least that was the initial thinking. And that was, I thought, intuitive and cool. And one of my postdoc mentors, John McCarthy, would talk about this all the time. It always really captured my imagination. And so I was like, cool. Well, I want to study this MIT protein. It goes on. It turns on with resistance training in the muscle fiber. I don't really know what it's doing. There's a lot of speculation, but there hasn't been any really concrete data. And I think it would be a cool thing to study.
07:36
Speaker 1
I just want to say, like, at some point I'm going to say it. So I'm going to say it now. Like, I want to be super clear. Lifting weights doesn't increase the risk of cancer, right? If anything, it reduces it, right?
07:45
Speaker 2
Yes, I would argue that's true. And that gets me back to what I'm going to say here is, like, the MYC gene turns on and the gene gets expressed and the protein comes on. But it's fast. It goes up. It's like a matter. It comes up a matter of hours. It's back down. It's a transient, you know, very, very kind of quick process.
08:04
Speaker 1
This is the good, healthy, not going to give you cancer way to express Nick.
08:09
Speaker 2
Exactly. Exactly. Well, it's like anything in life, you know, like timing is everything. And like, you know, like.
08:15
Speaker 1
Those makes the poison. Exactly. Exactly.
08:17
Speaker 2
This makes point. So like in this case, we're turning on just enough to get it to go do some stuff. But then we put it back to where it was, which is basically zero, the zero level.
08:26
Speaker 1
And when you came along, was it sort of mysterious? Like, what's it doing? Like, maybe it's making the muscle bigger, but we don't know exactly. Like, what are you setting out to find out?
08:34
Speaker 2
Yeah, that's correct.
08:35
Speaker 1
Yeah.
08:36
Speaker 2
The question was, what is it doing? Yeah. Like, that was the question. Because the thing is that we knew that we couldn't just go turn it on, right? Like, the answer to the question wouldn't be simple. Like, oh, well, because that's usually how people approach it. Like, something goes on with exercise. We go to the gym. We lift a weight. A gene comes on, a protein gets made, and we want to figure out what that thing does. Well, what do we do? We just go and we just overexpress it. We don't turn it on. We crank it up to 11 and we leave it at 11.
09:03
Speaker 1
And the way you do that is basically by genetically engineering mice.
09:07
Speaker 2
That's one way to do it. That's a pretty typical approach.
09:09
Speaker 1
Yeah.
09:09
Speaker 2
And that's usually that's kind of the way most people approach things is you just you have found an interesting thing. Now I'm going to it goes up with exercise. Now I'm just going to overexpress it for the rest of its life of the rest of the life of the mouse. And then we'll figure out what it does. Well, the problem there is some things you can't do that with.
09:25
Speaker 1
Because it would cause cancer. It would clearly not do the thing you're interested in.
09:30
Speaker 2
No, absolutely not. We know it's going up. We know it's coming on. We know it's this transient event. But I can't test it by just turning it on like I would a variety of other things because I don't. pretty sure the outcome is going to be death or something really bad. And so we had to come up with a way to turn the gene on and off. And so that's what we did. Not for Mick specifically, for just turning on things in general and then turning them off. And I saw an opportunity there. I was like, oh, well, there's a mouse model where I can... basically breed these mice together and get the result I want, which is turn Mick on at any point in the lifespan of a mouse for as long as I want. So I can turn it off really quick, turn it on off really quick, or I can leave it on for a while if I want to, whatever. But this is what I need to answer my question. And this is what's been missing. Again, up until pretty recently, people just turn things on and leave them on. That works for some things, doesn't work for a lot of other things. And I was trying to capture the exercise response. So something goes up, comes back down. So that's how we approached it, is we used this mouse model to kind of turn it on in a way that mimicked the exercise response. And when we did that, we found some really interesting things. We found that like, In certain muscle types, the muscle fibers got bigger. But at the same time, the capacity for oxidative metabolism increased, so potentially increasing endurance capacity. But also we found that there was this fiber-type transition from the more fast type to the more slow type. So we're seeing this hypertrophy. We're also seeing this fiber-type transition towards a more kind of endurance phase.
11:09
Speaker 1
So the muscle's getting bigger. Hypertrophages means the muscle's getting bigger. And it's shifting from this kind of quick power muscle to the more sort of endurance.
11:20
Speaker 2
Becoming a little bit more fatigue resistant, potentially.
11:22
Speaker 1
Yeah, yeah, yeah. And this is not from like a different training regime. This is just from expressing this protein.
11:28
Speaker 2
A little bit at a time over the course of like four to eight weeks, just turning it on for a couple hours. We would do a 48-hour pulse and then turn it off and leave it off for five days and then just repeat that. And then we found that this sort of mimicked several different aspects of exercise.
11:44
Speaker 1
So you describe in the paper, or at least one of the papers you wrote about this, you talk about– The pulses, right? You're pulsing the MYC. That it facilitates adaptability and a more youthful phenotype. Phenotype is just sort of what the muscle cell looks like, what it is. Looks like, how it behaves, yeah. So what does a more youthful phenotype mean? Like, that sounds promising. That sounds good to me. Everybody wants a more youthful phenotype.
12:11
Speaker 2
I talked about MYC as an oncogene. But it's also something else. It's also something called a Yamanaka factor, right? So what is a Yamanaka factor, right? Your listeners probably don't know, and that's fine because I didn't until a handful of years ago too. So basically a Yamanaka factor is named after a guy named Shinya Yamanaka. He won the Nobel Prize alongside Sir John B. Gurdon for the idea that you can epigenetically make a cell younger. Let's say a skin cell. I take some of your skin cells. I put them in a dish and I overexpress the Yamanaka factors.
12:46
Speaker 1
And the Yamanaka factors are just proteins, proteins that are naturally expressed by your body, right? That's correct. Four of them or something. There's four of them. That's right. Yeah.
12:54
Speaker 2
That's absolutely right. And we overexpress those or you can overexpress those in that cell, that skin cell, and it's Committed to being a skin cell. Like it's gone through its whole thing and now it's like reached the end of its life.
13:05
Speaker 1
Skin cell for life. I'm a skin cell. Literally ride or die.
13:07
Speaker 2
Skin cell forever. And so you take those skin cells, you put them in the dish, you overexpress. the Yamanaka factors, and then it turned back into an induced pluripotent stem cell.
13:17
Speaker 1
Which, to be clear, basically like an embryonic cell from the very beginning of life, which is very useful for lots of clinical and kind of research things, potentially. It's a huge deal. It's why it's like a very robust Nobel Prize. You know what? Two Nobel Prizes.
13:31
Speaker 2
Exactly. A very robust Nobel Prize, a way to describe it, right? And so basically what it does, though, is it takes the cell that's, you know, I guess my age, right? And and epigenetically reverses it to like a younger state that's more plastic that you can then turn into anything else. So I could take that skin cell and then say, okay, now I'm going to provide the cues to turn it into an eye cell or a brain cell or a heart cell. Right.
13:55
Speaker 1
So just to state it clearly, it takes a differentiated adult cell, like a skin cell, turns it into a stem cell, which is a cell like in a very, very, you know, new embryo. And the magic of stem cells is they can become any kind of cell in the body given the right genetic signal. That's right. And so this is incredible because You know, theoretically, you could have all kinds of cellular therapies using people's own cells. You know, I could take my skin cells and turn them into a new eye or something is the dream. You can't do that. That's the dream. Okay. So I get that. That's out there in the world. And so it turns out one of these Yamanaka factors, one of these four proteins that do this is MYC. Is this protein we're talking about? Why does that matter now? Like, it seems a little reductive to be like, see, it's making it younger. And that's what it's doing here. Is that what you're saying? And is that true?
14:44
Speaker 2
So what I'm saying is, you know, we know that exercise is good, right? We know that when you're older and you exercise, you become more functional and your muscle starts to behave more like when it was younger. So my thinking was what could be driving that, right?
14:58
Speaker 1
Right.
14:59
Speaker 2
And then my thinking was, okay, well, we know that mick turns on in the muscle when you exercise. The other yamanaka factors really do not.
15:08
Speaker 1
So, okay, so you've got this idea. Exercise helps keep you young physiologically. The yamanaka factor, there's this one yamanaka factor that is associated with exercise. Mick, keep going.
15:20
Speaker 2
Could it be one of the things that makes muscle change? healthier as you age. So basically the way we're approaching this now is like, can we just turn Mick on a little bit in the muscle fiber of old animals and get them to start behaving like younger muscles, start making them stronger, metabolically healthier, just by this one factor, right? It was sort of the thought process. And our initial studies are being indicated that like, when you turn on Mick just a little bit, at least at the epigenetic level. So at the level of like, you know, um, not your genes, but the things that are kind of controlling whether your genes turn on or off, it's kind of reshaping that to look more like a younger cell and whether that's going to translate to hypertrophy or adaptability or all the other things that go along with this kind.
16:06
Speaker 1
Of like, in other words, meaningful clinical changes. Yeah.
16:09
Speaker 2
Age reversal is, is, is what I'm, is what I'm working on. But, um, but it's been really interesting and promising, I think, to, uh, to kind of go after this because it's such a challenging question, but we have some cool tools that allow us to try and answer it. But the obvious, I think, question, at least to me and to other scientists in the field that I talk to, and every time I go to a conference or give a talk on this is like, how do you translate this to therapy, right? Like how do you take an oncogene and make it therapy?
16:38
Speaker 1
Um, Sounds sketchy.
16:41
Speaker 2
I think the simple answer is you don't. Like, you try to understand what the oncogene does.
16:45
Speaker 1
I don't want you messing around with a gene that's going to give you cancer if you mess around with it wrong, right?
16:49
Speaker 2
No, I think that would be unwise.
16:51
Speaker 1
I agree.
16:51
Speaker 2
And so I think the answer to that question is, you know, like anything, it's like, if we can understand the nuts and bolts of what it's doing, we can leverage those targets as opposed to the thing itself, right? Like, so Nick is turning on a bunch of different processes in the cell. What are these prostheses? Which ones are really that important for adaptation or for making muscle appear younger? And if we can identify those, then those are things that we can potentially target.
17:16
Speaker 1
So go a level in. Correct. Like, MYC is sort of too blunt a tool. It's doing too much, and you want to be more precisely targeted.
17:24
Speaker 2
I think that's a fair way to put it, yeah. Because, yeah, MYC is a blunt tool. I mean, they say it targets up to 15% of all our genes, which means, like, we put a MYC protein in a cell, it could potentially go and interact with 15% of our genes.
17:39
Speaker 1
Which is a lot, to be clear. That means like it's wild how much it is doing.
17:42
Speaker 2
Yeah, that's a wild amount for one protein to interact with. And so the question is like, what are the most important things it's doing? And can we leverage those to, you know, work towards therapy, work towards things that actually could become therapeutic for people that can exercise or need to increase the efficacy of their exercise? It's sort of the thought process.
18:06
Speaker 1
We'll be back in just a minute. So the dream is that you could have some drug therapy, say, that is useful. Like if people, I don't know, go to space or have a stroke or do something where they have a lot of atrophy of their muscles, perhaps there's some intervention so that when they are able to start walking again or exercising again or whatever, They can regain function faster. I mean, if we're just projecting way out to what the dream would be.
18:44
Speaker 2
It either prevents the loss from happening or allows you to regain more quickly.
18:48
Speaker 1
Right.
18:49
Speaker 2
I think it's important to understand, though, that like and as you say, this is basic research and basic research discoveries lead to incredible things all the time. I mean, look at like CRISPR that people were studying, like yogurt cultures, you know, like did they ever think that that was going to lead to what it's led to, like the revolution in gene therapy and gene editing? Yeah, of course not. I'm not saying that that's what's going to come out of this. Like, I have no idea what's going to come out of this. That's the fun part. But, you know, just exploring what this thing does and trying to understand it. And, you know, we know that when we turn it on for brief periods of time, we capture a lot of different aspects of exercise adaptation.
19:21
Speaker 1
So there is this idea that you can measure the biological age, so to speak, of a cell. And different kinds of cells have different kinds of– some people call them clocks or ages– Do I recall seeing somewhere that you have done that with muscle cells with MYC? Tried to see by standard measures of cellular age, does MYC infect make muscle cells younger when expressed in this way?
19:44
Speaker 2
We've done it with exercise, and we are doing it with MYC. We're just getting our first data back on that. So you're catching us at the, you know, the steep part of the curve and generating the data.
19:54
Speaker 1
And so what have you found? So with exercise, it's exercise in muscle cells?
19:58
Speaker 2
Yeah, exercise. So like what we've done, what I've done personally and what others have done to a human muscle, but I think maybe my paper was the first to measure it, but We did it in animals, right, where we exercised them late in life, right? So we took some older mice and we had them run on these wheels that have these weights. So it's like actual exercise for mice. Like you put a mouse on a running wheel that doesn't have weight on it or just in general, they love it. Like they just do that naturally. And, you know, you've probably heard the experiments where they put running wheels out in fields. It's a classic experiment. They put a running wheel out in a field and look to see if animals would just get on it naturally and start doing... And they do.
20:37
Speaker 1
I love that. That's how I feel when I go for a jog, right? You go for a jog. I live in Brooklyn and there's a big park where people run. And on a nice day, especially, there's hundreds of people just running around the big loop in the park. It's like we're all on the wheel. But happily. But we like it.
20:52
Speaker 2
You guys are all the rodents that want to exercise.
20:54
Speaker 1
That's great. Yeah.
20:56
Speaker 2
I hope nobody takes offense to that.
20:58
Speaker 1
Um, no, I mean, you know, there's the occasional real rodent in Brooklyn. That's a different story that you got to hop over sometimes.
21:04
Speaker 2
So anyway, we put these mice in these voluntary exercise wheels and then we put a little weight on the wheel to give them some extra resistance because we wanted to basically treat it like kind of resistance and aerobic training. And so we did that with these older mice and we, we weighted the wheels up like progressively like you would with resistance training. So added a little more weight every other week or every week. Um, And yeah, what we found is when we did that and we took the muscles when they got late in life, so like 24-month-old mice, which are probably equivalent to about late 60s, early 70s, kind of aged, equivalent to a human, we found that the epigenetic age of these mice was basically stopped at the point at which they exercised for the most part, as far as that prediction goes.
21:48
Speaker 1
They stopped getting older.
21:49
Speaker 2
From an epigenetic standpoint, yeah.
21:52
Speaker 1
What does that mean?
21:53
Speaker 2
The epigenetic landscape of your cells tends to change pretty systematically and predictably across the lifespan.
21:59
Speaker 1
And this basically means the way genes are turned on and off?
22:03
Speaker 2
Yes. In some capacity, yes. And that's kind of where people have grasped onto this because people came to the realization that, like, you can take two 70-year-olds, let's say, But the 70-year-old that's really, really healthy and takes good care of himself may have a younger appearing epigenetic profile. And vice versa, somebody who has had an unhealthy lifestyle, sedentary, poor diet, smoked, alcohol, the whole things, it can move that epigenetic age forward. So like chronologically, they might both be 70 years old. But biologically, the healthy one might look more like a 50-year-old.
22:35
Speaker 1
And have risks accordingly.
22:37
Speaker 2
And have risks accordingly. So all of this, now that we've given the background on epigenetic aging clocks, Are these changes that we see in the epigenome, the things that are then leading to greater health, up for debate?
22:50
Speaker 1
You would think so. You would hope.
22:52
Speaker 2
But you know what? I think determining causation and something like that is very, very difficult.
22:58
Speaker 1
Yeah, fair.
22:59
Speaker 2
But I think what we can say is that it aligns pretty well. It tends to align pretty well. Not in all circumstances.
23:04
Speaker 1
Yeah.
23:05
Speaker 2
But it tends to align pretty well.
23:06
Speaker 1
Let me ask you. Kind of going back more specifically to the Mick research. So you basically did it in mice. Has anybody done anything in people to try and figure out if it's the same? Should I assume that it's the same? Should I be wary?
23:21
Speaker 2
I don't think it's safe to assume it's the same, but I think in many instances, you know, foundational discoveries that are you know, fundamental biology and mice a lot of times will hold up in humans.
23:33
Speaker 1
But I mean, what do we know for sure about mick in humans of this conversation? You know, your specific studies about sort of pulsing it on demand has been in mice. What do we know for sure about that?
23:42
Speaker 2
I think the right question. I think what we can say with a fair amount of certainty is that, you know, when you take muscle samples from humans after exercise, we see that that and this is what inspired us to do some of our studies was like we did a study where we looked at the time course of response to exercise after a single bout, and we found that in the human muscle, Mick went up and came back down, right? So I think that's what we can say about right now about Mick and muscle.
24:08
Speaker 1
When you work out now, when you lift weights now, like, are you thinking about Mick? Do you think about like this protein flooding your....
24:16
Speaker 2
I'm thinking about a lot of things when I lift weights. It's probably not bad. But sometimes, I mean, I don't know if I want it to flood. I think I'd want a little bit. But yeah, yeah, yeah. And, you know, there's a lot of questions that go through my head. But yeah, I think it's something that does cross my mind from time to time. Like, what are the different processes? Or what's the thing regulated? That's the question I get a lot. Like, well, if Mick turns on, what's its trigger? What's the thing maybe up at the cell membrane that triggers this that then tells this to go turn Mick on? And it's like, I don't have answers to that question yet.
24:44
Speaker 1
I know you're working on lots of things, but is there like one when you think about sort of the frontier of your work, the thing you're trying to figure out now, is there one question you're particularly eager to answer you think would be really useful to answer that is kind of out there that you're working on or working towards?
24:59
Speaker 2
I mean, I think I want to kind of present a unified framework for how exercise is beneficial when you're young and how that can be leveraged when you're old. And I'm using kind of Mick as my starting point for that because I think it's really, really influential. But I think, you know, like trying to understand how it is that maybe the adaptive potential of muscle, in addition to muscle, like getting smaller throughout the lifespan and all these things we talked about, how is it that we can increase the adaptability of muscle? And I think there are some molecular targets and cues that are happening that are disrupted when you're aged. that we could potentially tap into and try to fix. And that's why I'm starting with Mick, because when you're young, you see this really nice pulse of Mick. But when you're old, you don't.
25:48
Speaker 1
Oh, interesting.
25:49
Speaker 2
And so at least the literature suggests this, right? That the Mick response seems to be blunted when you're older.
25:56
Speaker 1
So therefore, if Mick is key to the benefits of lifting weights, then you get less benefit when you get older. Although clearly there is some benefit, but that's the implication.
26:05
Speaker 2
But there are things that maybe aren't coming on or either aren't getting turned on at all or appropriately or at the right time, then that's potentially leading to some of these decrements and adaptation that may be The exercise response may be blunted. Well, it does seem like it's blunted when you're older. It's still great. But it's just, you know, when you get older, things don't always respond the same. So that's kind of what we're sort of trying to go after right now. And we're expanding that search into some other transcription factors and trying to find some translational avenues around Mick and stuff like that. So that's the things that are getting me excited in my own research program right now. Yeah.
26:41
Speaker 1
Yeah. We'll be back in a minute with the lightning round. For the lightning round, I wanted to do something a little more practical. I asked Kevin how his own workouts have changed as he's gotten older.
27:06
Speaker 2
I've tried to transition towards kind of just doing some with my lifting, more higher rep sort of things. Um, not being so concerned with lifting the heaviest weight and being the strongest I can be because, frankly, I just get injured. So I've kind of gravitated more towards doing the higher rep sort of things and kind of making my workouts a little– my lifting workouts a little bit quicker. I don't dwell in the gym for two hours anymore. I don't– in college, I would. No longer. Don't have the time for that. But so shorter workouts, higher reps, just trying to knock it out because– My shtick, I guess I say, is a little bit of exercise can go a long way.
27:41
Speaker 1
Like the marginal amount, right? Like if you're starting at zero, doing a little is a huge impact, right?
27:47
Speaker 2
But I think about this too. Like I'm only loading my muscle heavily for maybe two hours, not continuously, like periodically over the course of two hours, over my entire week. And yet I'm accruing muscle mass and I'm maintaining muscle mass through that, just that little bit of stimulation, right? You know, and I think that's really powerful. Like it just goes to show that like, you know, I'm not trying to be a bodybuilder here. And most people aren't. But like you can go and lift weights for an hour or a couple times a week and maybe hit the different muscles. And that's sufficient to maintain and to gain in many instances. And that's the beauty of resistance training, I think, is like it's really bang for your buck. You know, like you get a lot of benefit from not that much time in the gym. And also, though, the thing I think that's important in that and we're now we're just now we're really getting zooming out macro. These are just like general recommendations. It's like the key. It's not some secret recipe. It's like consistency. You know, like if you can be consistent and what comes and what creates consistency is doing something you enjoy, you know, like. I think it's important to be uncomfortable sometimes. And, like, I don't love doing cardio, but.
28:58
Speaker 1
Yes. Well, there is... What do they call it? Is it type 2 fun? Like, sometimes I enjoy being uncomfortable, right? Like, running up a hill fast, I actually enjoy. Maybe not at the very, very end, but... Yeah, I enjoy not enjoying it. I enjoy not enjoying it.
29:16
Speaker 2
It's okay to be uncomfortable. You know, being uncomfortable is not... Maybe not all the time, but it's just a good thing.
29:20
Speaker 1
Well, the idea also... I mean, this is the most macro is that like, like you're just going to do it for the rest of your life. Like part of why I exercise is so that I can exercise for the rest of my life. Right. Like I literally never want to stop. Yeah, exactly.
29:34
Speaker 2
I mean, I feel like I would be a really blessed and fortunate person if I could be exercising when I'm 80. Yeah. I think that would be really, really incredible.
29:41
Speaker 1
I mean, focusing on resistance training, like, does the way you should train change? Like, I'm particularly interested in middle age.
29:51
Speaker 2
Right, yeah.
29:52
Speaker 1
Not only because I'm in my 50s, but, like, you know, does... Do I need to think about it differently now than I might have.
30:00
Speaker 2
20 years ago? I don't know. I mean, I guess it depends on how you feel, right? But, you know, like I think kind of the classic antidote I sometimes hear by the aging lifters, right, is like, oh, I don't really do the heavy stuff anymore. I kind of go in and get more reps and, you know, kind of do the higher rep thing. But you can put on a lot of muscle mass and be strong, maybe not maximally strong, but be very strong by lifting, you know, some lighter weights and not crushing your tendons and your ligaments, too. And that's sort of what I've gravitated towards as I've gotten older. I mean, I'm 39 right now. I'll be 40 in March. And, you know, I think about these things a little bit, but also it's just I don't know. I don't I feel like I don't need to prove anything to anybody anymore. You know, as far as like how strong I am, that's not really like.
30:42
Speaker 1
It's the beauty of getting older. I still want to prove more than I want. Yeah. Like you want to not care about anything. You want to be a nice person and feel like we have nothing to prove in the world. Yeah.
30:52
Speaker 2
So I definitely don't go to the gym and like try to keep up with the younger guys. I'm just like, yeah, that's cool, man. Like you guys do your thing. I'm going to just kind of try to maintain as best I can. Yeah.
31:09
Speaker 1
Kevin Murok is an associate professor of nutrition, exercise physiology, and medical pharmacology and physiology at the University of Missouri. Today's show was produced by Gabriel Hunter Chang, engineered by Sarah Bruguier, and our showrunner and editor is Jake Harper. I'm Jacob Goldstein.
The Host
