1 00:00:15,396 --> 00:00:22,516 Speaker 1: Pushkin. What happens to our muscle cells as we get older? 2 00:00:23,196 --> 00:00:23,456 Speaker 2: Poof. 3 00:00:24,716 --> 00:00:40,096 Speaker 1: Nothing good. Sounds bad. I'm Jacob Goldstein. This is What's 4 00:00:40,116 --> 00:00:43,696 Speaker 1: Your Problem? And my guest today is Kevin Murek. Kevin 5 00:00:43,816 --> 00:00:47,316 Speaker 1: is a professor at the University of Missouri. He studies 6 00:00:47,396 --> 00:00:51,246 Speaker 1: muscle cells, and his problem is this. Can we understand 7 00:00:51,346 --> 00:00:53,526 Speaker 1: what's going on in our muscle cells when we do 8 00:00:53,586 --> 00:00:57,506 Speaker 1: things like lift weights? And can we use that understanding 9 00:00:57,866 --> 00:01:01,746 Speaker 1: to help people stay healthier as they age? As you 10 00:01:01,766 --> 00:01:03,766 Speaker 1: may have noticed, this is the second week in a 11 00:01:03,826 --> 00:01:07,096 Speaker 1: row that I'm interviewing a scientist who studies muscle cells 12 00:01:07,156 --> 00:01:10,276 Speaker 1: and aging and how exercise can help blunt the problems 13 00:01:10,316 --> 00:01:13,576 Speaker 1: of aging. And I'm doing these interviews now because I 14 00:01:13,616 --> 00:01:16,836 Speaker 1: feel like we are at this incredibly exciting moment in 15 00:01:16,896 --> 00:01:19,926 Speaker 1: the science of fitness and aging. It's been clear for 16 00:01:19,956 --> 00:01:22,266 Speaker 1: a long time that exercise is really good for us 17 00:01:22,386 --> 00:01:26,066 Speaker 1: in lots of different ways. But scientists are just now 18 00:01:26,166 --> 00:01:30,956 Speaker 1: starting to really understand at the cellular level why exercise 19 00:01:30,996 --> 00:01:34,856 Speaker 1: is so good. Kevin and I discussed this powerful protein 20 00:01:34,896 --> 00:01:39,386 Speaker 1: called MYC. spelled M-Y-C. Kevin has been studying MYC for 21 00:01:39,426 --> 00:01:41,766 Speaker 1: a while, and it may be a key part of 22 00:01:41,806 --> 00:01:45,566 Speaker 1: the reason that lifting weights and doing resistance training can 23 00:01:45,606 --> 00:01:49,506 Speaker 1: help us stay healthy and maybe even slow the aging process. 24 00:01:50,526 --> 00:01:53,926 Speaker 1: But to start, Kevin told me why scientists are suddenly 25 00:01:54,006 --> 00:01:57,726 Speaker 1: learning so much more about what goes on inside ourselves 26 00:01:57,906 --> 00:01:58,746 Speaker 1: as we exercise. 27 00:01:59,526 --> 00:02:02,386 Speaker 2: I think we're in a, everybody probably thinks whenever they're 28 00:02:02,406 --> 00:02:05,456 Speaker 2: working on in science that they're in some sort of renaissance, right? 29 00:02:05,476 --> 00:02:07,616 Speaker 2: Because whatever, whatever you're doing at the moment is like 30 00:02:07,646 --> 00:02:08,806 Speaker 2: the most cutting edge, cool thing. 31 00:02:09,086 --> 00:02:10,966 Speaker 1: Hopefully one hopes so. Yeah. 32 00:02:11,026 --> 00:02:14,286 Speaker 2: It's good. If you think that it's good, but you know, like, uh, 33 00:02:14,406 --> 00:02:17,086 Speaker 2: I think the renaissance of, of my age right now 34 00:02:17,186 --> 00:02:20,986 Speaker 2: is like all this single cell and single nucleus technology 35 00:02:21,026 --> 00:02:23,526 Speaker 2: that's come on board. And now in the last, really 36 00:02:23,566 --> 00:02:27,076 Speaker 2: the 10 last 10 years and really probably last six 37 00:02:27,116 --> 00:02:30,096 Speaker 2: or seven years in muscle. We've gotten into doing things 38 00:02:30,236 --> 00:02:33,876 Speaker 2: at like a single cell resolution. So like we'll say, okay, 39 00:02:33,916 --> 00:02:37,866 Speaker 2: here's a single nucleus from a muscle fiber that we're 40 00:02:37,876 --> 00:02:41,046 Speaker 2: going to analyze. Here's a single stem cell. Here's a 41 00:02:41,126 --> 00:02:44,506 Speaker 2: single immune cell. We're going to look at all of 42 00:02:44,586 --> 00:02:50,726 Speaker 2: these individual constituents and what they're expressing on an individual 43 00:02:50,826 --> 00:02:53,596 Speaker 2: cell and nucleus level. Whereas before we were just getting 44 00:02:53,636 --> 00:02:57,456 Speaker 2: like kind of a mashed up aggregate snapshot. Now we're 45 00:02:57,496 --> 00:03:00,636 Speaker 2: able to kind of say, oh, wow, like this particular 46 00:03:00,696 --> 00:03:05,626 Speaker 2: cell type, this nucleus here is doing this in response 47 00:03:05,726 --> 00:03:09,246 Speaker 2: to exercise. And what does that mean? It's incredible. Like 48 00:03:09,266 --> 00:03:12,566 Speaker 2: the technology to me is mind blowing. I'm sure like 49 00:03:12,766 --> 00:03:15,206 Speaker 2: I think everybody does science in a given moment probably 50 00:03:15,246 --> 00:03:16,876 Speaker 2: says that about whatever it is they're doing. And they're 51 00:03:16,896 --> 00:03:18,816 Speaker 2: like the mind is blown by the technology. 52 00:03:19,116 --> 00:03:20,876 Speaker 1: I know. I mean, I know you have looked at 53 00:03:21,296 --> 00:03:25,236 Speaker 1: at cell level behavior, gene expression in the context of both. 54 00:03:25,646 --> 00:03:29,006 Speaker 1: resistance training and exercise in muscle cells, right? 55 00:03:29,026 --> 00:03:29,346 Speaker 2: Yep. 56 00:03:29,886 --> 00:03:35,456 Speaker 1: You have found a protein called MYC. M-Y-C. It's pronounced MYC. 57 00:03:35,776 --> 00:03:35,896 Speaker 2: Sure. 58 00:03:36,116 --> 00:03:39,076 Speaker 1: And that seems important in the context of resistance training 59 00:03:39,096 --> 00:03:40,596 Speaker 1: and aging. Tell me about MYC. 60 00:03:41,056 --> 00:03:44,656 Speaker 2: MYC is what's called an oncoprotein, right? And so, or 61 00:03:44,696 --> 00:03:48,536 Speaker 2: an oncogene. And it's probably one of the more studied 62 00:03:48,796 --> 00:03:49,656 Speaker 2: oncogenes out there. 63 00:03:49,776 --> 00:03:51,436 Speaker 1: Onco, like oncology? Like cancer? 64 00:03:51,476 --> 00:03:53,036 Speaker 2: Onco, like onc, or onco, like cancer. 65 00:03:53,076 --> 00:03:53,556 Speaker 1: Yeah, exactly. 66 00:03:53,576 --> 00:03:56,036 Speaker 2: And the reason why it's called an oncogene is because 67 00:03:56,196 --> 00:03:59,856 Speaker 2: when it gets dysregulated, so like if it acquires a 68 00:03:59,896 --> 00:04:03,876 Speaker 2: mutation that turns it on too much, like basically it's 69 00:04:03,976 --> 00:04:07,156 Speaker 2: usually not on. Usually it's off. It only turns on 70 00:04:07,196 --> 00:04:11,116 Speaker 2: in response to specific things. But if you mutate that gene, 71 00:04:11,156 --> 00:04:13,446 Speaker 2: turn it on all the time, that cell turns into 72 00:04:13,486 --> 00:04:15,586 Speaker 2: a tumor. So you mutate this one gene. 73 00:04:15,946 --> 00:04:16,126 Speaker 1: Yeah. 74 00:04:16,546 --> 00:04:18,966 Speaker 2: You get a tumor. Or you get a cancerous cell 75 00:04:18,986 --> 00:04:19,846 Speaker 2: that can become a tumor. 76 00:04:20,066 --> 00:04:22,406 Speaker 1: And just as a point of clarity, I called it 77 00:04:22,466 --> 00:04:23,846 Speaker 1: a protein. You're calling it a gene. I mean, it's 78 00:04:23,866 --> 00:04:26,766 Speaker 1: basically the gene that expresses the protein. The gene that 79 00:04:26,806 --> 00:04:30,646 Speaker 1: expresses the protein is Nick. Bingo. So if it's mutated 80 00:04:30,706 --> 00:04:32,706 Speaker 1: and makes this protein all the time, that's bad. 81 00:04:32,946 --> 00:04:33,386 Speaker 2: That's bad. 82 00:04:33,406 --> 00:04:35,726 Speaker 1: You get cancer and you don't want cancer. Okay. And 83 00:04:35,766 --> 00:04:38,156 Speaker 1: that we knew. That's the kind of what we knew 84 00:04:38,266 --> 00:04:41,076 Speaker 1: before you came along. So we know it's an oncogene. 85 00:04:41,116 --> 00:04:42,736 Speaker 1: What else do we know about it? Why were people 86 00:04:42,816 --> 00:04:44,696 Speaker 1: interested in muscle adaptation? 87 00:04:45,106 --> 00:04:48,916 Speaker 2: Yes. So basically it had been recognized and also my 88 00:04:48,996 --> 00:04:51,856 Speaker 2: work had shown that it gets turned on in response 89 00:04:51,916 --> 00:04:55,116 Speaker 2: to resistance exercise, specifically in the muscle fiber. It has 90 00:04:55,196 --> 00:04:57,596 Speaker 2: functions in the body like any other gene does. It's 91 00:04:57,616 --> 00:05:00,156 Speaker 2: just when it gets dysregulated, it has this really negative 92 00:05:00,176 --> 00:05:02,216 Speaker 2: thing associated with it. So that's what kind of gives 93 00:05:02,296 --> 00:05:03,376 Speaker 2: it its name. 94 00:05:03,396 --> 00:05:04,276 Speaker 1: Bad reputation. 95 00:05:04,476 --> 00:05:05,716 Speaker 2: That's what gives us bad reputation. 96 00:05:05,736 --> 00:05:05,836 Speaker 1: Sure. 97 00:05:05,856 --> 00:05:07,236 Speaker 2: But it's just a gene like any other. It does 98 00:05:07,276 --> 00:05:08,836 Speaker 2: all types of things. It's important for a lot of 99 00:05:08,876 --> 00:05:11,356 Speaker 2: functions in the body, but only in small amounts. It's 100 00:05:11,416 --> 00:05:15,256 Speaker 2: tightly regulated like for a reason. It's powerful. Because it's 101 00:05:15,296 --> 00:05:17,696 Speaker 2: a transcription factor, which means that it's a protein that 102 00:05:17,736 --> 00:05:19,836 Speaker 2: can go, once it gets made, it can go into 103 00:05:19,856 --> 00:05:22,936 Speaker 2: the nucleus and then turn on a whole bunch of 104 00:05:23,056 --> 00:05:25,606 Speaker 2: other genes, right? So that's what a transcription factor does. 105 00:05:25,966 --> 00:05:28,406 Speaker 1: So just to be clear, what MYC does, it sort 106 00:05:28,426 --> 00:05:32,406 Speaker 1: of goes back to the DNA and says, whatever, you 107 00:05:32,546 --> 00:05:35,486 Speaker 1: particular gene, turn on right now. That is what MYC does. 108 00:05:35,906 --> 00:05:38,926 Speaker 2: Yeah, or you hundreds of genes turn on because we 109 00:05:38,966 --> 00:05:40,826 Speaker 2: need to do X, Y, or Z, and it's going 110 00:05:40,846 --> 00:05:41,886 Speaker 2: to require all of us. 111 00:05:41,946 --> 00:05:45,406 Speaker 1: Yeah, Right. It's never one. It's always so complicated. Yeah, yeah, yeah. 112 00:05:45,466 --> 00:05:46,536 Speaker 2: It's always so complicated. 113 00:05:46,556 --> 00:05:49,096 Speaker 1: Does it also turn things off? Yeah, sure. 114 00:05:49,316 --> 00:05:50,076 Speaker 2: Yeah, it certainly can. 115 00:05:50,316 --> 00:05:52,916 Speaker 1: So it's a protein that turns other genes on and 116 00:05:52,976 --> 00:05:56,136 Speaker 1: off to express many other proteins or not express them. Okay, 117 00:05:56,156 --> 00:05:57,496 Speaker 1: so that's basically what it does. 118 00:05:58,036 --> 00:05:59,796 Speaker 2: So it goes in the nucleus, it turns on other genes. 119 00:05:59,816 --> 00:06:01,616 Speaker 2: So when you lift a weight, you go to the gym, 120 00:06:01,696 --> 00:06:05,336 Speaker 2: the nuclei inside your muscle fibers, and again, there's hundreds 121 00:06:05,456 --> 00:06:08,116 Speaker 2: to thousands of those in each individual muscle fiber, and 122 00:06:08,156 --> 00:06:10,586 Speaker 2: you may have like five or 600,000 of those in 123 00:06:10,626 --> 00:06:14,436 Speaker 2: your vastus lateralis, right? the nuclei inside of those individual 124 00:06:14,476 --> 00:06:18,236 Speaker 2: muscle fibers will turn this gene on. And that, to me, 125 00:06:18,296 --> 00:06:20,516 Speaker 2: was really cool because I was like, oh, it's an oncogene. 126 00:06:21,176 --> 00:06:24,476 Speaker 2: It's turning on. What's it doing? Like, why would you 127 00:06:24,496 --> 00:06:28,276 Speaker 2: want to turn on an oncogene in response to exercise? 128 00:06:28,836 --> 00:06:32,856 Speaker 2: But the thing is with really cancer in general, though, 129 00:06:32,896 --> 00:06:36,356 Speaker 2: like what is cancer really? It's uncontrolled growth. It's a 130 00:06:36,396 --> 00:06:39,506 Speaker 2: growth program. And so when I go to the gym 131 00:06:39,546 --> 00:06:44,086 Speaker 2: and lift a weight, I'm turning on growth programs. 132 00:06:44,326 --> 00:06:45,446 Speaker 1: To grow the muscle cells. 133 00:06:45,466 --> 00:06:49,356 Speaker 2: To grow the muscle cells. And so you're using, biology 134 00:06:49,456 --> 00:06:51,836 Speaker 2: uses a lot of the same things for different purposes. 135 00:06:52,036 --> 00:06:58,296 Speaker 2: And a cancer cell will turn on MYC and proliferate. 136 00:06:58,616 --> 00:07:01,696 Speaker 2: The muscle fiber doesn't really proliferate. It's not like you're 137 00:07:01,736 --> 00:07:05,226 Speaker 2: making more muscle fibers. You're just making the existing ones bigger. 138 00:07:05,586 --> 00:07:07,596 Speaker 1: Right. That's what happens when we lift weights, to be clear. 139 00:07:07,616 --> 00:07:09,566 Speaker 1: It's not that you get more muscle cells. It's the 140 00:07:09,596 --> 00:07:12,336 Speaker 1: muscle cells you have, the muscle fibers you have get bigger. 141 00:07:12,716 --> 00:07:17,236 Speaker 2: Precisely. And the muscle cell seems to be using the 142 00:07:17,356 --> 00:07:21,256 Speaker 2: same kind of cancer program to make itself bigger. And 143 00:07:21,456 --> 00:07:24,276 Speaker 2: at least that was the initial thinking. And that was, 144 00:07:24,336 --> 00:07:27,756 Speaker 2: I thought, intuitive and cool. And one of my postdoc mentors, 145 00:07:27,856 --> 00:07:29,496 Speaker 2: John McCarthy, would talk about this all the time. It 146 00:07:29,516 --> 00:07:33,036 Speaker 2: always really captured my imagination. And so I was like, cool. Well, 147 00:07:33,056 --> 00:07:35,936 Speaker 2: I want to study this MIT protein. It goes on. 148 00:07:36,196 --> 00:07:38,536 Speaker 2: It turns on with resistance training in the muscle fiber. 149 00:07:39,736 --> 00:07:41,116 Speaker 2: I don't really know what it's doing. There's a lot 150 00:07:41,136 --> 00:07:43,616 Speaker 2: of speculation, but there hasn't been any really concrete data. 151 00:07:43,756 --> 00:07:45,136 Speaker 2: And I think it would be a cool thing to study. 152 00:07:45,656 --> 00:07:47,316 Speaker 1: I just want to say, like, at some point I'm 153 00:07:47,336 --> 00:07:48,756 Speaker 1: going to say it. So I'm going to say it now. Like, 154 00:07:48,856 --> 00:07:51,716 Speaker 1: I want to be super clear. Lifting weights doesn't increase 155 00:07:51,736 --> 00:07:54,556 Speaker 1: the risk of cancer, right? If anything, it reduces it, right? 156 00:07:54,616 --> 00:07:56,696 Speaker 2: Yes, I would argue that's true. And that gets me 157 00:07:56,756 --> 00:07:59,136 Speaker 2: back to what I'm going to say here is, like, 158 00:07:59,466 --> 00:08:02,526 Speaker 2: the MYC gene turns on and the gene gets expressed 159 00:08:02,546 --> 00:08:05,546 Speaker 2: and the protein comes on. But it's fast. It goes up. 160 00:08:05,876 --> 00:08:08,016 Speaker 2: It's like a matter. It comes up a matter of hours. 161 00:08:08,076 --> 00:08:12,286 Speaker 2: It's back down. It's a transient, you know, very, very 162 00:08:12,366 --> 00:08:14,086 Speaker 2: kind of quick process. 163 00:08:14,106 --> 00:08:16,626 Speaker 1: This is the good, healthy, not going to give you 164 00:08:16,686 --> 00:08:18,606 Speaker 1: cancer way to express Nick. 165 00:08:18,766 --> 00:08:22,106 Speaker 2: Exactly. Exactly. Well, it's like anything in life, you know, 166 00:08:22,206 --> 00:08:24,706 Speaker 2: like timing is everything. And like, you know, like. 167 00:08:24,616 --> 00:08:27,036 Speaker 1: Those makes the poison. Exactly. Exactly. 168 00:08:27,056 --> 00:08:28,776 Speaker 2: This makes point. So like in this case, we're turning 169 00:08:28,836 --> 00:08:31,256 Speaker 2: on just enough to get it to go do some stuff. 170 00:08:31,896 --> 00:08:33,556 Speaker 2: But then we put it back to where it was, 171 00:08:33,606 --> 00:08:35,626 Speaker 2: which is basically zero, the zero level. 172 00:08:35,786 --> 00:08:38,546 Speaker 1: And when you came along, was it sort of mysterious? Like, 173 00:08:38,646 --> 00:08:40,606 Speaker 1: what's it doing? Like, maybe it's making the muscle bigger, 174 00:08:40,646 --> 00:08:42,606 Speaker 1: but we don't know exactly. Like, what are you setting 175 00:08:42,666 --> 00:08:43,486 Speaker 1: out to find out? 176 00:08:43,746 --> 00:08:44,966 Speaker 2: Yeah, that's correct. 177 00:08:45,006 --> 00:08:45,206 Speaker 1: Yeah. 178 00:08:45,246 --> 00:08:48,646 Speaker 2: The question was, what is it doing? Yeah. Like, that 179 00:08:48,666 --> 00:08:50,596 Speaker 2: was the question. Because the thing is that we knew 180 00:08:50,656 --> 00:08:53,776 Speaker 2: that we couldn't just go turn it on, right? Like, 181 00:08:54,116 --> 00:08:56,036 Speaker 2: the answer to the question wouldn't be simple. Like, oh, well, 182 00:08:56,076 --> 00:08:58,656 Speaker 2: because that's usually how people approach it. Like, something goes 183 00:08:58,736 --> 00:09:00,576 Speaker 2: on with exercise. We go to the gym. We lift 184 00:09:00,616 --> 00:09:03,196 Speaker 2: a weight. A gene comes on, a protein gets made, 185 00:09:03,676 --> 00:09:05,736 Speaker 2: and we want to figure out what that thing does. Well, 186 00:09:05,756 --> 00:09:07,096 Speaker 2: what do we do? We just go and we just 187 00:09:07,416 --> 00:09:09,516 Speaker 2: overexpress it. We don't turn it on. We crank it 188 00:09:09,576 --> 00:09:12,236 Speaker 2: up to 11 and we leave it at 11. 189 00:09:12,236 --> 00:09:15,116 Speaker 1: And the way you do that is basically by genetically 190 00:09:15,156 --> 00:09:15,976 Speaker 1: engineering mice. 191 00:09:16,176 --> 00:09:18,556 Speaker 2: That's one way to do it. That's a pretty typical approach. 192 00:09:18,596 --> 00:09:18,756 Speaker 1: Yeah. 193 00:09:18,776 --> 00:09:21,296 Speaker 2: And that's usually that's kind of the way most people 194 00:09:21,316 --> 00:09:24,016 Speaker 2: approach things is you just you have found an interesting thing. 195 00:09:24,066 --> 00:09:25,846 Speaker 2: Now I'm going to it goes up with exercise. Now 196 00:09:25,886 --> 00:09:28,026 Speaker 2: I'm just going to overexpress it for the rest of 197 00:09:28,086 --> 00:09:29,606 Speaker 2: its life of the rest of the life of the mouse. 198 00:09:29,886 --> 00:09:31,866 Speaker 2: And then we'll figure out what it does. Well, the 199 00:09:31,906 --> 00:09:34,366 Speaker 2: problem there is some things you can't do that with. 200 00:09:35,026 --> 00:09:37,726 Speaker 1: Because it would cause cancer. It would clearly not do 201 00:09:37,806 --> 00:09:39,116 Speaker 1: the thing you're interested in. 202 00:09:39,166 --> 00:09:41,516 Speaker 2: No, absolutely not. We know it's going up. We know 203 00:09:41,576 --> 00:09:44,996 Speaker 2: it's coming on. We know it's this transient event. But 204 00:09:45,456 --> 00:09:47,436 Speaker 2: I can't test it by just turning it on like 205 00:09:47,476 --> 00:09:50,356 Speaker 2: I would a variety of other things because I don't. 206 00:09:50,686 --> 00:09:54,446 Speaker 2: pretty sure the outcome is going to be death or 207 00:09:54,486 --> 00:09:56,936 Speaker 2: something really bad. And so we had to come up 208 00:09:56,976 --> 00:09:59,216 Speaker 2: with a way to turn the gene on and off. 209 00:09:59,396 --> 00:10:02,036 Speaker 2: And so that's what we did. Not for Mick specifically, 210 00:10:02,076 --> 00:10:04,446 Speaker 2: for just turning on things in general and then turning 211 00:10:04,486 --> 00:10:07,026 Speaker 2: them off. And I saw an opportunity there. I was like, oh, well, 212 00:10:07,046 --> 00:10:10,166 Speaker 2: there's a mouse model where I can... basically breed these 213 00:10:10,206 --> 00:10:12,386 Speaker 2: mice together and get the result I want, which is 214 00:10:13,126 --> 00:10:16,576 Speaker 2: turn Mick on at any point in the lifespan of 215 00:10:16,596 --> 00:10:19,896 Speaker 2: a mouse for as long as I want. So I 216 00:10:19,916 --> 00:10:21,656 Speaker 2: can turn it off really quick, turn it on off 217 00:10:21,716 --> 00:10:23,096 Speaker 2: really quick, or I can leave it on for a 218 00:10:23,116 --> 00:10:25,296 Speaker 2: while if I want to, whatever. But this is what 219 00:10:25,376 --> 00:10:29,086 Speaker 2: I need to answer my question. And this is what's 220 00:10:29,106 --> 00:10:33,226 Speaker 2: been missing. Again, up until pretty recently, people just turn 221 00:10:33,246 --> 00:10:35,946 Speaker 2: things on and leave them on. That works for some things, 222 00:10:36,026 --> 00:10:37,726 Speaker 2: doesn't work for a lot of other things. And I 223 00:10:37,746 --> 00:10:40,716 Speaker 2: was trying to capture the exercise response. So something goes up, 224 00:10:40,796 --> 00:10:43,556 Speaker 2: comes back down. So that's how we approached it, is 225 00:10:43,636 --> 00:10:46,476 Speaker 2: we used this mouse model to kind of turn it 226 00:10:46,636 --> 00:10:50,376 Speaker 2: on in a way that mimicked the exercise response. And 227 00:10:50,436 --> 00:10:52,786 Speaker 2: when we did that, we found some really interesting things. 228 00:10:52,826 --> 00:10:56,316 Speaker 2: We found that like, In certain muscle types, the muscle 229 00:10:56,336 --> 00:11:00,016 Speaker 2: fibers got bigger. But at the same time, the capacity 230 00:11:00,606 --> 00:11:06,306 Speaker 2: for oxidative metabolism increased, so potentially increasing endurance capacity. But 231 00:11:06,446 --> 00:11:09,626 Speaker 2: also we found that there was this fiber-type transition from 232 00:11:09,666 --> 00:11:12,126 Speaker 2: the more fast type to the more slow type. So 233 00:11:12,146 --> 00:11:15,586 Speaker 2: we're seeing this hypertrophy. We're also seeing this fiber-type transition 234 00:11:15,606 --> 00:11:17,126 Speaker 2: towards a more kind of endurance phase. 235 00:11:18,116 --> 00:11:21,556 Speaker 1: So the muscle's getting bigger. Hypertrophages means the muscle's getting bigger. 236 00:11:21,956 --> 00:11:25,666 Speaker 1: And it's shifting from this kind of quick power muscle 237 00:11:25,826 --> 00:11:28,246 Speaker 1: to the more sort of endurance. 238 00:11:29,366 --> 00:11:31,646 Speaker 2: Becoming a little bit more fatigue resistant, potentially. 239 00:11:31,826 --> 00:11:34,026 Speaker 1: Yeah, yeah, yeah. And this is not from like a 240 00:11:34,046 --> 00:11:37,196 Speaker 1: different training regime. This is just from expressing this protein. 241 00:11:37,636 --> 00:11:39,556 Speaker 2: A little bit at a time over the course of 242 00:11:39,616 --> 00:11:41,456 Speaker 2: like four to eight weeks, just turning it on for 243 00:11:41,476 --> 00:11:44,236 Speaker 2: a couple hours. We would do a 48-hour pulse and 244 00:11:44,256 --> 00:11:46,076 Speaker 2: then turn it off and leave it off for five 245 00:11:46,116 --> 00:11:48,456 Speaker 2: days and then just repeat that. And then we found 246 00:11:48,496 --> 00:11:53,056 Speaker 2: that this sort of mimicked several different aspects of exercise. 247 00:11:53,316 --> 00:11:56,376 Speaker 1: So you describe in the paper, or at least one 248 00:11:56,396 --> 00:12:00,176 Speaker 1: of the papers you wrote about this, you talk about– 249 00:12:00,716 --> 00:12:04,176 Speaker 1: The pulses, right? You're pulsing the MYC. That it facilitates 250 00:12:04,456 --> 00:12:08,936 Speaker 1: adaptability and a more youthful phenotype. Phenotype is just sort 251 00:12:08,956 --> 00:12:12,176 Speaker 1: of what the muscle cell looks like, what it is. 252 00:12:12,176 --> 00:12:14,446 Speaker 1: Looks like, how it behaves, yeah. So what does a 253 00:12:14,486 --> 00:12:17,886 Speaker 1: more youthful phenotype mean? Like, that sounds promising. That sounds 254 00:12:18,046 --> 00:12:20,986 Speaker 1: good to me. Everybody wants a more youthful phenotype. 255 00:12:21,066 --> 00:12:24,916 Speaker 2: I talked about MYC as an oncogene. But it's also 256 00:12:24,976 --> 00:12:28,086 Speaker 2: something else. It's also something called a Yamanaka factor, right? 257 00:12:28,166 --> 00:12:31,766 Speaker 2: So what is a Yamanaka factor, right? Your listeners probably 258 00:12:31,786 --> 00:12:33,726 Speaker 2: don't know, and that's fine because I didn't until a 259 00:12:33,746 --> 00:12:36,946 Speaker 2: handful of years ago too. So basically a Yamanaka factor 260 00:12:37,166 --> 00:12:39,496 Speaker 2: is named after a guy named Shinya Yamanaka. He won 261 00:12:39,516 --> 00:12:43,316 Speaker 2: the Nobel Prize alongside Sir John B. Gurdon for the 262 00:12:43,396 --> 00:12:48,106 Speaker 2: idea that you can epigenetically make a cell younger. Let's 263 00:12:48,136 --> 00:12:50,686 Speaker 2: say a skin cell. I take some of your skin cells. 264 00:12:51,196 --> 00:12:54,076 Speaker 2: I put them in a dish and I overexpress the 265 00:12:54,096 --> 00:12:55,196 Speaker 2: Yamanaka factors. 266 00:12:55,396 --> 00:12:58,556 Speaker 1: And the Yamanaka factors are just proteins, proteins that are 267 00:12:58,596 --> 00:13:01,176 Speaker 1: naturally expressed by your body, right? That's correct. Four of 268 00:13:01,236 --> 00:13:03,016 Speaker 1: them or something. There's four of them. That's right. Yeah. 269 00:13:03,256 --> 00:13:06,606 Speaker 2: That's absolutely right. And we overexpress those or you can 270 00:13:06,646 --> 00:13:09,686 Speaker 2: overexpress those in that cell, that skin cell, and it's 271 00:13:10,316 --> 00:13:12,116 Speaker 2: Committed to being a skin cell. Like it's gone through 272 00:13:12,136 --> 00:13:13,756 Speaker 2: its whole thing and now it's like reached the end 273 00:13:13,776 --> 00:13:14,156 Speaker 2: of its life. 274 00:13:14,216 --> 00:13:16,136 Speaker 1: Skin cell for life. I'm a skin cell. Literally ride 275 00:13:16,186 --> 00:13:16,586 Speaker 1: or die. 276 00:13:17,106 --> 00:13:19,586 Speaker 2: Skin cell forever. And so you take those skin cells, 277 00:13:19,606 --> 00:13:22,776 Speaker 2: you put them in the dish, you overexpress. the Yamanaka factors, 278 00:13:23,236 --> 00:13:26,786 Speaker 2: and then it turned back into an induced pluripotent stem cell. 279 00:13:27,006 --> 00:13:29,686 Speaker 1: Which, to be clear, basically like an embryonic cell from 280 00:13:29,706 --> 00:13:32,646 Speaker 1: the very beginning of life, which is very useful for 281 00:13:32,706 --> 00:13:36,046 Speaker 1: lots of clinical and kind of research things, potentially. It's 282 00:13:36,106 --> 00:13:38,596 Speaker 1: a huge deal. It's why it's like a very robust 283 00:13:38,636 --> 00:13:40,696 Speaker 1: Nobel Prize. You know what? Two Nobel Prizes. 284 00:13:40,796 --> 00:13:43,976 Speaker 2: Exactly. A very robust Nobel Prize, a way to describe it, right? 285 00:13:43,996 --> 00:13:46,136 Speaker 2: And so basically what it does, though, is it takes 286 00:13:46,196 --> 00:13:49,466 Speaker 2: the cell that's, you know, I guess my age, right? 287 00:13:49,586 --> 00:13:53,186 Speaker 2: And and epigenetically reverses it to like a younger state 288 00:13:53,306 --> 00:13:56,506 Speaker 2: that's more plastic that you can then turn into anything else. 289 00:13:56,526 --> 00:13:58,376 Speaker 2: So I could take that skin cell and then say, okay, 290 00:13:58,396 --> 00:14:00,236 Speaker 2: now I'm going to provide the cues to turn it 291 00:14:00,256 --> 00:14:03,146 Speaker 2: into an eye cell or a brain cell or a 292 00:14:03,186 --> 00:14:04,366 Speaker 2: heart cell. Right. 293 00:14:04,406 --> 00:14:07,686 Speaker 1: So just to state it clearly, it takes a differentiated 294 00:14:07,706 --> 00:14:09,866 Speaker 1: adult cell, like a skin cell, turns it into a 295 00:14:10,386 --> 00:14:12,996 Speaker 1: stem cell, which is a cell like in a very, very, 296 00:14:13,216 --> 00:14:15,756 Speaker 1: you know, new embryo. And the magic of stem cells 297 00:14:15,836 --> 00:14:17,856 Speaker 1: is they can become any kind of cell in the 298 00:14:17,896 --> 00:14:20,466 Speaker 1: body given the right genetic signal. That's right. And so 299 00:14:20,496 --> 00:14:24,326 Speaker 1: this is incredible because You know, theoretically, you could have 300 00:14:24,366 --> 00:14:27,806 Speaker 1: all kinds of cellular therapies using people's own cells. You know, 301 00:14:27,826 --> 00:14:29,726 Speaker 1: I could take my skin cells and turn them into 302 00:14:29,766 --> 00:14:31,586 Speaker 1: a new eye or something is the dream. You can't 303 00:14:31,606 --> 00:14:34,546 Speaker 1: do that. That's the dream. Okay. So I get that. 304 00:14:34,596 --> 00:14:36,856 Speaker 1: That's out there in the world. And so it turns 305 00:14:36,916 --> 00:14:39,536 Speaker 1: out one of these Yamanaka factors, one of these four 306 00:14:39,596 --> 00:14:42,656 Speaker 1: proteins that do this is MYC. Is this protein we're 307 00:14:42,676 --> 00:14:46,716 Speaker 1: talking about? Why does that matter now? Like, it seems 308 00:14:46,756 --> 00:14:49,576 Speaker 1: a little reductive to be like, see, it's making it younger. 309 00:14:49,596 --> 00:14:52,056 Speaker 1: And that's what it's doing here. Is that what you're saying? 310 00:14:52,096 --> 00:14:52,836 Speaker 1: And is that true? 311 00:14:53,116 --> 00:14:55,196 Speaker 2: So what I'm saying is, you know, we know that 312 00:14:55,276 --> 00:14:58,216 Speaker 2: exercise is good, right? We know that when you're older 313 00:14:58,356 --> 00:15:01,726 Speaker 2: and you exercise, you become more functional and your muscle 314 00:15:01,736 --> 00:15:04,446 Speaker 2: starts to behave more like when it was younger. So 315 00:15:04,486 --> 00:15:07,786 Speaker 2: my thinking was what could be driving that, right? 316 00:15:07,986 --> 00:15:08,226 Speaker 1: Right. 317 00:15:09,106 --> 00:15:11,716 Speaker 2: And then my thinking was, okay, well, we know that 318 00:15:11,866 --> 00:15:15,476 Speaker 2: mick turns on in the muscle when you exercise. The 319 00:15:15,516 --> 00:15:17,376 Speaker 2: other yamanaka factors really do not. 320 00:15:17,656 --> 00:15:21,016 Speaker 1: So, okay, so you've got this idea. Exercise helps keep 321 00:15:21,056 --> 00:15:24,976 Speaker 1: you young physiologically. The yamanaka factor, there's this one yamanaka 322 00:15:24,996 --> 00:15:28,886 Speaker 1: factor that is associated with exercise. Mick, keep going. 323 00:15:29,186 --> 00:15:32,306 Speaker 2: Could it be one of the things that makes muscle change? 324 00:15:32,876 --> 00:15:36,336 Speaker 2: healthier as you age. So basically the way we're approaching 325 00:15:36,376 --> 00:15:39,036 Speaker 2: this now is like, can we just turn Mick on 326 00:15:39,086 --> 00:15:41,306 Speaker 2: a little bit in the muscle fiber of old animals 327 00:15:41,366 --> 00:15:44,746 Speaker 2: and get them to start behaving like younger muscles, start 328 00:15:45,246 --> 00:15:49,206 Speaker 2: making them stronger, metabolically healthier, just by this one factor, right? 329 00:15:49,226 --> 00:15:51,476 Speaker 2: It was sort of the thought process. And our initial 330 00:15:51,506 --> 00:15:54,476 Speaker 2: studies are being indicated that like, when you turn on 331 00:15:54,536 --> 00:15:58,356 Speaker 2: Mick just a little bit, at least at the epigenetic level. 332 00:15:58,396 --> 00:16:00,616 Speaker 2: So at the level of like, you know, um, not 333 00:16:00,656 --> 00:16:02,956 Speaker 2: your genes, but the things that are kind of controlling 334 00:16:02,976 --> 00:16:05,556 Speaker 2: whether your genes turn on or off, it's kind of 335 00:16:05,596 --> 00:16:09,296 Speaker 2: reshaping that to look more like a younger cell and 336 00:16:09,346 --> 00:16:13,386 Speaker 2: whether that's going to translate to hypertrophy or adaptability or 337 00:16:13,426 --> 00:16:15,686 Speaker 2: all the other things that go along with this kind. 338 00:16:15,546 --> 00:16:18,066 Speaker 1: Of like, in other words, meaningful clinical changes. Yeah. 339 00:16:18,246 --> 00:16:20,526 Speaker 2: Age reversal is, is, is what I'm, is what I'm 340 00:16:20,546 --> 00:16:25,306 Speaker 2: working on. But, um, but it's been really interesting and promising, 341 00:16:25,386 --> 00:16:28,336 Speaker 2: I think, to, uh, to kind of go after this 342 00:16:28,396 --> 00:16:31,766 Speaker 2: because it's such a challenging question, but we have some 343 00:16:31,786 --> 00:16:33,846 Speaker 2: cool tools that allow us to try and answer it. 344 00:16:34,346 --> 00:16:37,226 Speaker 2: But the obvious, I think, question, at least to me 345 00:16:37,266 --> 00:16:39,186 Speaker 2: and to other scientists in the field that I talk to, 346 00:16:39,246 --> 00:16:40,616 Speaker 2: and every time I go to a conference or give 347 00:16:40,646 --> 00:16:43,156 Speaker 2: a talk on this is like, how do you translate 348 00:16:43,196 --> 00:16:44,916 Speaker 2: this to therapy, right? Like how do you take an 349 00:16:45,016 --> 00:16:47,516 Speaker 2: oncogene and make it therapy? 350 00:16:48,036 --> 00:16:49,876 Speaker 1: Um, Sounds sketchy. 351 00:16:50,216 --> 00:16:52,376 Speaker 2: I think the simple answer is you don't. Like, you 352 00:16:52,396 --> 00:16:54,146 Speaker 2: try to understand what the oncogene does. 353 00:16:54,206 --> 00:16:56,226 Speaker 1: I don't want you messing around with a gene that's 354 00:16:56,246 --> 00:16:58,106 Speaker 1: going to give you cancer if you mess around with 355 00:16:58,186 --> 00:16:58,906 Speaker 1: it wrong, right? 356 00:16:58,926 --> 00:17:00,266 Speaker 2: No, I think that would be unwise. 357 00:17:00,366 --> 00:17:00,746 Speaker 1: I agree. 358 00:17:00,806 --> 00:17:02,926 Speaker 2: And so I think the answer to that question is, 359 00:17:02,966 --> 00:17:06,116 Speaker 2: you know, like anything, it's like, if we can understand 360 00:17:06,496 --> 00:17:08,976 Speaker 2: the nuts and bolts of what it's doing, we can 361 00:17:09,036 --> 00:17:14,076 Speaker 2: leverage those targets as opposed to the thing itself, right? Like, 362 00:17:14,096 --> 00:17:15,946 Speaker 2: so Nick is turning on a bunch of different processes 363 00:17:15,996 --> 00:17:18,626 Speaker 2: in the cell. What are these prostheses? Which ones are 364 00:17:18,646 --> 00:17:21,496 Speaker 2: really that important for adaptation or for making muscle appear younger? 365 00:17:22,386 --> 00:17:24,706 Speaker 2: And if we can identify those, then those are things 366 00:17:24,726 --> 00:17:25,716 Speaker 2: that we can potentially target. 367 00:17:25,916 --> 00:17:28,696 Speaker 1: So go a level in. Correct. Like, MYC is sort 368 00:17:28,716 --> 00:17:31,596 Speaker 1: of too blunt a tool. It's doing too much, and 369 00:17:31,636 --> 00:17:33,496 Speaker 1: you want to be more precisely targeted. 370 00:17:33,736 --> 00:17:36,956 Speaker 2: I think that's a fair way to put it, yeah. Because, yeah, 371 00:17:36,996 --> 00:17:39,906 Speaker 2: MYC is a blunt tool. I mean, they say it 372 00:17:40,006 --> 00:17:42,986 Speaker 2: targets up to 15% of all our genes, which means, like, 373 00:17:43,226 --> 00:17:45,426 Speaker 2: we put a MYC protein in a cell, it could 374 00:17:45,446 --> 00:17:47,366 Speaker 2: potentially go and interact with 15% of our genes. 375 00:17:48,386 --> 00:17:50,306 Speaker 1: Which is a lot, to be clear. That means like 376 00:17:50,436 --> 00:17:51,896 Speaker 1: it's wild how much it is doing. 377 00:17:51,916 --> 00:17:54,756 Speaker 2: Yeah, that's a wild amount for one protein to interact with. 378 00:17:55,316 --> 00:17:56,936 Speaker 2: And so the question is like, what are the most 379 00:17:56,996 --> 00:18:00,556 Speaker 2: important things it's doing? And can we leverage those to, 380 00:18:01,096 --> 00:18:03,596 Speaker 2: you know, work towards therapy, work towards things that actually 381 00:18:03,656 --> 00:18:06,686 Speaker 2: could become therapeutic for people that can exercise or need 382 00:18:06,706 --> 00:18:10,486 Speaker 2: to increase the efficacy of their exercise? It's sort of 383 00:18:10,506 --> 00:18:11,546 Speaker 2: the thought process. 384 00:18:15,466 --> 00:18:29,456 Speaker 1: We'll be back in just a minute. So the dream 385 00:18:29,576 --> 00:18:34,336 Speaker 1: is that you could have some drug therapy, say, that 386 00:18:34,396 --> 00:18:37,156 Speaker 1: is useful. Like if people, I don't know, go to 387 00:18:37,176 --> 00:18:39,446 Speaker 1: space or have a stroke or do something where they 388 00:18:39,486 --> 00:18:43,506 Speaker 1: have a lot of atrophy of their muscles, perhaps there's 389 00:18:43,526 --> 00:18:45,906 Speaker 1: some intervention so that when they are able to start 390 00:18:46,026 --> 00:18:49,716 Speaker 1: walking again or exercising again or whatever, They can regain 391 00:18:49,776 --> 00:18:51,876 Speaker 1: function faster. I mean, if we're just projecting way out 392 00:18:51,916 --> 00:18:52,876 Speaker 1: to what the dream would be. 393 00:18:53,136 --> 00:18:56,316 Speaker 2: It either prevents the loss from happening or allows you 394 00:18:56,336 --> 00:18:57,376 Speaker 2: to regain more quickly. 395 00:18:57,536 --> 00:18:57,736 Speaker 1: Right. 396 00:18:58,226 --> 00:19:00,446 Speaker 2: I think it's important to understand, though, that like and 397 00:19:00,566 --> 00:19:03,146 Speaker 2: as you say, this is basic research and basic research 398 00:19:03,186 --> 00:19:05,926 Speaker 2: discoveries lead to incredible things all the time. I mean, 399 00:19:05,946 --> 00:19:08,706 Speaker 2: look at like CRISPR that people were studying, like yogurt cultures, 400 00:19:08,726 --> 00:19:10,946 Speaker 2: you know, like did they ever think that that was 401 00:19:10,976 --> 00:19:12,596 Speaker 2: going to lead to what it's led to, like the 402 00:19:12,656 --> 00:19:15,556 Speaker 2: revolution in gene therapy and gene editing? Yeah, of course not. 403 00:19:15,876 --> 00:19:17,336 Speaker 2: I'm not saying that that's what's going to come out 404 00:19:17,376 --> 00:19:18,476 Speaker 2: of this. Like, I have no idea what's going to 405 00:19:18,496 --> 00:19:19,916 Speaker 2: come out of this. That's the fun part. But, you know, 406 00:19:19,966 --> 00:19:23,306 Speaker 2: just exploring what this thing does and trying to understand it. And, 407 00:19:23,506 --> 00:19:24,766 Speaker 2: you know, we know that when we turn it on 408 00:19:24,786 --> 00:19:27,666 Speaker 2: for brief periods of time, we capture a lot of 409 00:19:27,706 --> 00:19:29,766 Speaker 2: different aspects of exercise adaptation. 410 00:19:30,706 --> 00:19:33,166 Speaker 1: So there is this idea that you can measure the 411 00:19:33,226 --> 00:19:36,346 Speaker 1: biological age, so to speak, of a cell. And different 412 00:19:36,386 --> 00:19:38,326 Speaker 1: kinds of cells have different kinds of– some people call 413 00:19:38,346 --> 00:19:43,176 Speaker 1: them clocks or ages– Do I recall seeing somewhere that 414 00:19:43,256 --> 00:19:45,976 Speaker 1: you have done that with muscle cells with MYC? Tried 415 00:19:46,016 --> 00:19:49,506 Speaker 1: to see by standard measures of cellular age, does MYC 416 00:19:49,566 --> 00:19:53,306 Speaker 1: infect make muscle cells younger when expressed in this way? 417 00:19:53,326 --> 00:19:55,386 Speaker 2: We've done it with exercise, and we are doing it 418 00:19:55,606 --> 00:19:58,326 Speaker 2: with MYC. We're just getting our first data back on that. 419 00:19:58,486 --> 00:20:01,736 Speaker 2: So you're catching us at the, you know, the steep 420 00:20:01,766 --> 00:20:03,156 Speaker 2: part of the curve and generating the data. 421 00:20:03,216 --> 00:20:05,956 Speaker 1: And so what have you found? So with exercise, it's 422 00:20:06,016 --> 00:20:07,216 Speaker 1: exercise in muscle cells? 423 00:20:07,416 --> 00:20:10,656 Speaker 2: Yeah, exercise. So like what we've done, what I've done 424 00:20:10,716 --> 00:20:13,336 Speaker 2: personally and what others have done to a human muscle, 425 00:20:13,376 --> 00:20:15,856 Speaker 2: but I think maybe my paper was the first to 426 00:20:15,896 --> 00:20:18,336 Speaker 2: measure it, but We did it in animals, right, where 427 00:20:18,356 --> 00:20:21,396 Speaker 2: we exercised them late in life, right? So we took 428 00:20:21,716 --> 00:20:24,556 Speaker 2: some older mice and we had them run on these 429 00:20:24,596 --> 00:20:27,826 Speaker 2: wheels that have these weights. So it's like actual exercise 430 00:20:27,886 --> 00:20:29,926 Speaker 2: for mice. Like you put a mouse on a running 431 00:20:29,966 --> 00:20:33,246 Speaker 2: wheel that doesn't have weight on it or just in general, 432 00:20:33,266 --> 00:20:35,316 Speaker 2: they love it. Like they just do that naturally. And, 433 00:20:35,346 --> 00:20:37,276 Speaker 2: you know, you've probably heard the experiments where they put 434 00:20:37,996 --> 00:20:40,936 Speaker 2: running wheels out in fields. It's a classic experiment. They 435 00:20:40,956 --> 00:20:42,796 Speaker 2: put a running wheel out in a field and look 436 00:20:42,836 --> 00:20:44,596 Speaker 2: to see if animals would just get on it naturally 437 00:20:44,646 --> 00:20:45,926 Speaker 2: and start doing... And they do. 438 00:20:46,146 --> 00:20:48,846 Speaker 1: I love that. That's how I feel when I go 439 00:20:48,886 --> 00:20:50,446 Speaker 1: for a jog, right? You go for a jog. I 440 00:20:50,486 --> 00:20:52,726 Speaker 1: live in Brooklyn and there's a big park where people run. 441 00:20:53,266 --> 00:20:55,966 Speaker 1: And on a nice day, especially, there's hundreds of people 442 00:20:56,046 --> 00:20:58,236 Speaker 1: just running around the big loop in the park. It's 443 00:20:58,276 --> 00:21:01,176 Speaker 1: like we're all on the wheel. But happily. But we 444 00:21:01,196 --> 00:21:01,396 Speaker 1: like it. 445 00:21:01,396 --> 00:21:03,376 Speaker 2: You guys are all the rodents that want to exercise. 446 00:21:03,396 --> 00:21:04,676 Speaker 1: That's great. Yeah. 447 00:21:05,986 --> 00:21:06,966 Speaker 2: I hope nobody takes offense to that. 448 00:21:07,366 --> 00:21:09,926 Speaker 1: Um, no, I mean, you know, there's the occasional real 449 00:21:09,986 --> 00:21:12,346 Speaker 1: rodent in Brooklyn. That's a different story that you got 450 00:21:12,366 --> 00:21:13,586 Speaker 1: to hop over sometimes. 451 00:21:14,046 --> 00:21:17,586 Speaker 2: So anyway, we put these mice in these voluntary exercise 452 00:21:17,626 --> 00:21:19,406 Speaker 2: wheels and then we put a little weight on the 453 00:21:19,446 --> 00:21:22,896 Speaker 2: wheel to give them some extra resistance because we wanted 454 00:21:22,936 --> 00:21:25,876 Speaker 2: to basically treat it like kind of resistance and aerobic training. 455 00:21:26,376 --> 00:21:28,576 Speaker 2: And so we did that with these older mice and we, 456 00:21:28,776 --> 00:21:31,116 Speaker 2: we weighted the wheels up like progressively like you would 457 00:21:31,156 --> 00:21:33,236 Speaker 2: with resistance training. So added a little more weight every 458 00:21:33,276 --> 00:21:36,136 Speaker 2: other week or every week. Um, And yeah, what we 459 00:21:36,176 --> 00:21:38,076 Speaker 2: found is when we did that and we took the 460 00:21:38,116 --> 00:21:41,176 Speaker 2: muscles when they got late in life, so like 24-month-old mice, 461 00:21:41,216 --> 00:21:44,726 Speaker 2: which are probably equivalent to about late 60s, early 70s, 462 00:21:44,776 --> 00:21:48,856 Speaker 2: kind of aged, equivalent to a human, we found that 463 00:21:48,916 --> 00:21:53,696 Speaker 2: the epigenetic age of these mice was basically stopped at 464 00:21:53,736 --> 00:21:55,876 Speaker 2: the point at which they exercised for the most part, 465 00:21:55,936 --> 00:21:57,186 Speaker 2: as far as that prediction goes. 466 00:21:57,206 --> 00:21:58,466 Speaker 1: They stopped getting older. 467 00:21:58,906 --> 00:22:01,146 Speaker 2: From an epigenetic standpoint, yeah. 468 00:22:01,366 --> 00:22:01,846 Speaker 1: What does that mean? 469 00:22:02,166 --> 00:22:06,546 Speaker 2: The epigenetic landscape of your cells tends to change pretty 470 00:22:06,606 --> 00:22:08,846 Speaker 2: systematically and predictably across the lifespan. 471 00:22:08,966 --> 00:22:11,526 Speaker 1: And this basically means the way genes are turned on 472 00:22:11,586 --> 00:22:11,936 Speaker 1: and off? 473 00:22:12,356 --> 00:22:15,036 Speaker 2: Yes. In some capacity, yes. And that's kind of where 474 00:22:15,056 --> 00:22:16,916 Speaker 2: people have grasped onto this because people came to the 475 00:22:16,956 --> 00:22:21,056 Speaker 2: realization that, like, you can take two 70-year-olds, let's say, 476 00:22:21,616 --> 00:22:24,396 Speaker 2: But the 70-year-old that's really, really healthy and takes good 477 00:22:24,436 --> 00:22:28,656 Speaker 2: care of himself may have a younger appearing epigenetic profile. 478 00:22:29,056 --> 00:22:32,716 Speaker 2: And vice versa, somebody who has had an unhealthy lifestyle, sedentary, 479 00:22:32,856 --> 00:22:35,696 Speaker 2: poor diet, smoked, alcohol, the whole things, it can move 480 00:22:35,716 --> 00:22:39,136 Speaker 2: that epigenetic age forward. So like chronologically, they might both 481 00:22:39,156 --> 00:22:42,146 Speaker 2: be 70 years old. But biologically, the healthy one might 482 00:22:42,166 --> 00:22:43,996 Speaker 2: look more like a 50-year-old. 483 00:22:44,166 --> 00:22:46,126 Speaker 1: And have risks accordingly. 484 00:22:46,606 --> 00:22:49,086 Speaker 2: And have risks accordingly. So all of this, now that 485 00:22:49,106 --> 00:22:52,576 Speaker 2: we've given the background on epigenetic aging clocks, Are these 486 00:22:52,616 --> 00:22:56,316 Speaker 2: changes that we see in the epigenome, the things that 487 00:22:56,336 --> 00:22:59,456 Speaker 2: are then leading to greater health, up for debate? 488 00:22:59,596 --> 00:23:01,496 Speaker 1: You would think so. You would hope. 489 00:23:01,656 --> 00:23:05,376 Speaker 2: But you know what? I think determining causation and something 490 00:23:05,416 --> 00:23:07,016 Speaker 2: like that is very, very difficult. 491 00:23:07,166 --> 00:23:08,126 Speaker 1: Yeah, fair. 492 00:23:08,446 --> 00:23:09,886 Speaker 2: But I think what we can say is that it 493 00:23:09,986 --> 00:23:12,666 Speaker 2: aligns pretty well. It tends to align pretty well. Not 494 00:23:12,686 --> 00:23:13,706 Speaker 2: in all circumstances. 495 00:23:14,006 --> 00:23:14,166 Speaker 1: Yeah. 496 00:23:14,286 --> 00:23:15,526 Speaker 2: But it tends to align pretty well. 497 00:23:15,786 --> 00:23:18,886 Speaker 1: Let me ask you. Kind of going back more specifically 498 00:23:18,926 --> 00:23:22,716 Speaker 1: to the Mick research. So you basically did it in mice. 499 00:23:24,156 --> 00:23:26,956 Speaker 1: Has anybody done anything in people to try and figure 500 00:23:26,976 --> 00:23:28,716 Speaker 1: out if it's the same? Should I assume that it's 501 00:23:28,756 --> 00:23:30,536 Speaker 1: the same? Should I be wary? 502 00:23:30,736 --> 00:23:34,056 Speaker 2: I don't think it's safe to assume it's the same, 503 00:23:34,096 --> 00:23:38,446 Speaker 2: but I think in many instances, you know, foundational discoveries 504 00:23:38,466 --> 00:23:41,246 Speaker 2: that are you know, fundamental biology and mice a lot 505 00:23:41,266 --> 00:23:42,186 Speaker 2: of times will hold up in humans. 506 00:23:42,226 --> 00:23:44,506 Speaker 1: But I mean, what do we know for sure about 507 00:23:44,566 --> 00:23:47,696 Speaker 1: mick in humans of this conversation? You know, your specific 508 00:23:47,736 --> 00:23:49,916 Speaker 1: studies about sort of pulsing it on demand has been 509 00:23:49,956 --> 00:23:51,756 Speaker 1: in mice. What do we know for sure about that? 510 00:23:51,776 --> 00:23:53,216 Speaker 2: I think the right question. I think what we can 511 00:23:53,256 --> 00:23:56,116 Speaker 2: say with a fair amount of certainty is that, you know, 512 00:23:56,196 --> 00:24:00,406 Speaker 2: when you take muscle samples from humans after exercise, we 513 00:24:00,466 --> 00:24:02,586 Speaker 2: see that that and this is what inspired us to 514 00:24:02,626 --> 00:24:04,026 Speaker 2: do some of our studies was like we did a 515 00:24:04,046 --> 00:24:07,236 Speaker 2: study where we looked at the time course of response 516 00:24:07,256 --> 00:24:10,356 Speaker 2: to exercise after a single bout, and we found that 517 00:24:10,496 --> 00:24:13,056 Speaker 2: in the human muscle, Mick went up and came back down, right? 518 00:24:13,116 --> 00:24:15,356 Speaker 2: So I think that's what we can say about right 519 00:24:15,416 --> 00:24:16,876 Speaker 2: now about Mick and muscle. 520 00:24:17,136 --> 00:24:19,236 Speaker 1: When you work out now, when you lift weights now, like, 521 00:24:19,356 --> 00:24:21,776 Speaker 1: are you thinking about Mick? Do you think about like 522 00:24:21,796 --> 00:24:23,746 Speaker 1: this protein flooding your.... 523 00:24:25,596 --> 00:24:27,296 Speaker 2: I'm thinking about a lot of things when I lift weights. 524 00:24:27,356 --> 00:24:30,496 Speaker 2: It's probably not bad. But sometimes, I mean, I don't 525 00:24:30,516 --> 00:24:32,036 Speaker 2: know if I want it to flood. I think I'd 526 00:24:32,076 --> 00:24:34,536 Speaker 2: want a little bit. But yeah, yeah, yeah. And, you know, 527 00:24:34,556 --> 00:24:36,206 Speaker 2: there's a lot of questions that go through my head. 528 00:24:36,726 --> 00:24:38,746 Speaker 2: But yeah, I think it's something that does cross my 529 00:24:38,786 --> 00:24:40,966 Speaker 2: mind from time to time. Like, what are the different processes? 530 00:24:40,986 --> 00:24:42,906 Speaker 2: Or what's the thing regulated? That's the question I get 531 00:24:42,926 --> 00:24:45,566 Speaker 2: a lot. Like, well, if Mick turns on, what's its trigger? 532 00:24:45,626 --> 00:24:48,026 Speaker 2: What's the thing maybe up at the cell membrane that 533 00:24:48,126 --> 00:24:50,406 Speaker 2: triggers this that then tells this to go turn Mick on? 534 00:24:50,446 --> 00:24:52,746 Speaker 2: And it's like, I don't have answers to that question yet. 535 00:24:53,236 --> 00:24:54,776 Speaker 1: I know you're working on lots of things, but is 536 00:24:54,796 --> 00:24:56,586 Speaker 1: there like one when you think about sort of the 537 00:24:56,646 --> 00:24:58,486 Speaker 1: frontier of your work, the thing you're trying to figure 538 00:24:58,526 --> 00:25:02,606 Speaker 1: out now, is there one question you're particularly eager to 539 00:25:02,726 --> 00:25:04,866 Speaker 1: answer you think would be really useful to answer that 540 00:25:04,926 --> 00:25:07,086 Speaker 1: is kind of out there that you're working on or 541 00:25:07,106 --> 00:25:07,806 Speaker 1: working towards? 542 00:25:08,266 --> 00:25:10,426 Speaker 2: I mean, I think I want to kind of present 543 00:25:10,906 --> 00:25:16,446 Speaker 2: a unified framework for how exercise is beneficial when you're 544 00:25:16,466 --> 00:25:19,086 Speaker 2: young and how that can be leveraged when you're old. 545 00:25:19,826 --> 00:25:22,386 Speaker 2: And I'm using kind of Mick as my starting point 546 00:25:22,406 --> 00:25:25,266 Speaker 2: for that because I think it's really, really influential. But 547 00:25:25,286 --> 00:25:28,446 Speaker 2: I think, you know, like trying to understand how it 548 00:25:28,626 --> 00:25:33,186 Speaker 2: is that maybe the adaptive potential of muscle, in addition 549 00:25:33,226 --> 00:25:35,526 Speaker 2: to muscle, like getting smaller throughout the lifespan and all 550 00:25:35,546 --> 00:25:38,246 Speaker 2: these things we talked about, how is it that we 551 00:25:38,286 --> 00:25:42,476 Speaker 2: can increase the adaptability of muscle? And I think there 552 00:25:42,516 --> 00:25:45,996 Speaker 2: are some molecular targets and cues that are happening that 553 00:25:46,016 --> 00:25:48,976 Speaker 2: are disrupted when you're aged. that we could potentially tap 554 00:25:49,036 --> 00:25:51,796 Speaker 2: into and try to fix. And that's why I'm starting 555 00:25:51,836 --> 00:25:54,556 Speaker 2: with Mick, because when you're young, you see this really 556 00:25:54,596 --> 00:25:57,176 Speaker 2: nice pulse of Mick. But when you're old, you don't. 557 00:25:57,436 --> 00:25:58,296 Speaker 1: Oh, interesting. 558 00:25:58,416 --> 00:26:02,336 Speaker 2: And so at least the literature suggests this, right? That 559 00:26:02,696 --> 00:26:05,356 Speaker 2: the Mick response seems to be blunted when you're older. 560 00:26:05,496 --> 00:26:08,716 Speaker 1: So therefore, if Mick is key to the benefits of 561 00:26:08,756 --> 00:26:11,736 Speaker 1: lifting weights, then you get less benefit when you get older. 562 00:26:11,776 --> 00:26:14,626 Speaker 1: Although clearly there is some benefit, but that's the implication. 563 00:26:14,666 --> 00:26:16,886 Speaker 2: But there are things that maybe aren't coming on or 564 00:26:17,046 --> 00:26:20,846 Speaker 2: either aren't getting turned on at all or appropriately or 565 00:26:20,886 --> 00:26:23,406 Speaker 2: at the right time, then that's potentially leading to some 566 00:26:23,446 --> 00:26:27,316 Speaker 2: of these decrements and adaptation that may be The exercise 567 00:26:27,336 --> 00:26:29,376 Speaker 2: response may be blunted. Well, it does seem like it's 568 00:26:29,396 --> 00:26:31,356 Speaker 2: blunted when you're older. It's still great. But it's just, 569 00:26:32,196 --> 00:26:34,556 Speaker 2: you know, when you get older, things don't always respond 570 00:26:34,576 --> 00:26:36,876 Speaker 2: the same. So that's kind of what we're sort of 571 00:26:36,916 --> 00:26:39,186 Speaker 2: trying to go after right now. And we're expanding that 572 00:26:39,226 --> 00:26:42,526 Speaker 2: search into some other transcription factors and trying to find 573 00:26:42,566 --> 00:26:46,106 Speaker 2: some translational avenues around Mick and stuff like that. So 574 00:26:46,386 --> 00:26:48,666 Speaker 2: that's the things that are getting me excited in my 575 00:26:48,726 --> 00:26:50,306 Speaker 2: own research program right now. Yeah. 576 00:26:50,326 --> 00:26:57,276 Speaker 1: Yeah. We'll be back in a minute with the lightning round. 577 00:27:08,356 --> 00:27:10,356 Speaker 1: For the lightning round, I wanted to do something a 578 00:27:10,396 --> 00:27:13,816 Speaker 1: little more practical. I asked Kevin how his own workouts 579 00:27:13,856 --> 00:27:15,496 Speaker 1: have changed as he's gotten older. 580 00:27:16,036 --> 00:27:18,876 Speaker 2: I've tried to transition towards kind of just doing some 581 00:27:19,016 --> 00:27:21,836 Speaker 2: with my lifting, more higher rep sort of things. Um, 582 00:27:22,336 --> 00:27:24,596 Speaker 2: not being so concerned with lifting the heaviest weight and 583 00:27:24,616 --> 00:27:26,616 Speaker 2: being the strongest I can be because, frankly, I just 584 00:27:26,636 --> 00:27:30,296 Speaker 2: get injured. So I've kind of gravitated more towards doing 585 00:27:30,316 --> 00:27:32,436 Speaker 2: the higher rep sort of things and kind of making 586 00:27:32,476 --> 00:27:34,916 Speaker 2: my workouts a little– my lifting workouts a little bit quicker. 587 00:27:34,946 --> 00:27:36,906 Speaker 2: I don't dwell in the gym for two hours anymore. 588 00:27:36,946 --> 00:27:39,506 Speaker 2: I don't– in college, I would. No longer. Don't have 589 00:27:39,526 --> 00:27:43,346 Speaker 2: the time for that. But so shorter workouts, higher reps, 590 00:27:43,406 --> 00:27:47,386 Speaker 2: just trying to knock it out because– My shtick, I 591 00:27:47,426 --> 00:27:49,146 Speaker 2: guess I say, is a little bit of exercise can 592 00:27:49,166 --> 00:27:49,946 Speaker 2: go a long way. 593 00:27:50,206 --> 00:27:53,246 Speaker 1: Like the marginal amount, right? Like if you're starting at zero, 594 00:27:53,326 --> 00:27:56,336 Speaker 1: doing a little is a huge impact, right? 595 00:27:56,376 --> 00:27:59,256 Speaker 2: But I think about this too. Like I'm only loading 596 00:27:59,316 --> 00:28:05,436 Speaker 2: my muscle heavily for maybe two hours, not continuously, like 597 00:28:05,456 --> 00:28:07,956 Speaker 2: periodically over the course of two hours, over my entire week. 598 00:28:08,576 --> 00:28:11,236 Speaker 2: And yet I'm accruing muscle mass and I'm maintaining muscle 599 00:28:11,256 --> 00:28:14,306 Speaker 2: mass through that, just that little bit of stimulation, right? 600 00:28:15,366 --> 00:28:18,326 Speaker 2: You know, and I think that's really powerful. Like it 601 00:28:18,346 --> 00:28:21,006 Speaker 2: just goes to show that like, you know, I'm not 602 00:28:21,026 --> 00:28:23,576 Speaker 2: trying to be a bodybuilder here. And most people aren't. 603 00:28:24,156 --> 00:28:27,216 Speaker 2: But like you can go and lift weights for an 604 00:28:27,256 --> 00:28:29,516 Speaker 2: hour or a couple times a week and maybe hit 605 00:28:29,536 --> 00:28:32,936 Speaker 2: the different muscles. And that's sufficient to maintain and to 606 00:28:32,976 --> 00:28:37,116 Speaker 2: gain in many instances. And that's the beauty of resistance training, 607 00:28:37,176 --> 00:28:40,116 Speaker 2: I think, is like it's really bang for your buck. 608 00:28:40,336 --> 00:28:42,476 Speaker 2: You know, like you get a lot of benefit from 609 00:28:42,656 --> 00:28:45,406 Speaker 2: not that much time in the gym. And also, though, 610 00:28:45,426 --> 00:28:47,126 Speaker 2: the thing I think that's important in that and we're 611 00:28:47,166 --> 00:28:49,486 Speaker 2: now we're just now we're really getting zooming out macro. 612 00:28:49,506 --> 00:28:52,706 Speaker 2: These are just like general recommendations. It's like the key. 613 00:28:52,846 --> 00:28:56,096 Speaker 2: It's not some secret recipe. It's like consistency. You know, 614 00:28:56,136 --> 00:28:58,336 Speaker 2: like if you can be consistent and what comes and 615 00:28:58,376 --> 00:29:01,736 Speaker 2: what creates consistency is doing something you enjoy, you know, like. 616 00:29:02,516 --> 00:29:04,586 Speaker 2: I think it's important to be uncomfortable sometimes. And, like, 617 00:29:04,986 --> 00:29:06,986 Speaker 2: I don't love doing cardio, but. 618 00:29:07,506 --> 00:29:09,426 Speaker 1: Yes. Well, there is... What do they call it? Is 619 00:29:09,486 --> 00:29:14,706 Speaker 1: it type 2 fun? Like, sometimes I enjoy being uncomfortable, right? Like, 620 00:29:15,086 --> 00:29:19,506 Speaker 1: running up a hill fast, I actually enjoy. Maybe not 621 00:29:19,526 --> 00:29:22,646 Speaker 1: at the very, very end, but... Yeah, I enjoy not 622 00:29:22,706 --> 00:29:24,986 Speaker 1: enjoying it. I enjoy not enjoying it. 623 00:29:25,216 --> 00:29:27,856 Speaker 2: It's okay to be uncomfortable. You know, being uncomfortable is not... 624 00:29:27,756 --> 00:29:29,356 Speaker 2: Maybe not all the time, but it's just a good thing. 625 00:29:29,416 --> 00:29:31,856 Speaker 1: Well, the idea also... I mean, this is the most 626 00:29:31,916 --> 00:29:34,436 Speaker 1: macro is that like, like you're just going to do 627 00:29:34,456 --> 00:29:36,776 Speaker 1: it for the rest of your life. Like part of 628 00:29:36,816 --> 00:29:39,456 Speaker 1: why I exercise is so that I can exercise for 629 00:29:39,476 --> 00:29:42,056 Speaker 1: the rest of my life. Right. Like I literally never 630 00:29:42,126 --> 00:29:43,826 Speaker 1: want to stop. Yeah, exactly. 631 00:29:43,866 --> 00:29:45,346 Speaker 2: I mean, I feel like I would be a really 632 00:29:45,386 --> 00:29:48,086 Speaker 2: blessed and fortunate person if I could be exercising when 633 00:29:48,106 --> 00:29:50,716 Speaker 2: I'm 80. Yeah. I think that would be really, really incredible. 634 00:29:50,736 --> 00:29:56,226 Speaker 1: I mean, focusing on resistance training, like, does the way 635 00:29:57,086 --> 00:30:01,006 Speaker 1: you should train change? Like, I'm particularly interested in middle age. 636 00:30:01,026 --> 00:30:01,866 Speaker 2: Right, yeah. 637 00:30:01,946 --> 00:30:05,166 Speaker 1: Not only because I'm in my 50s, but, like, you know, does... 638 00:30:06,686 --> 00:30:08,716 Speaker 1: Do I need to think about it differently now than 639 00:30:08,756 --> 00:30:09,336 Speaker 1: I might have. 640 00:30:09,196 --> 00:30:11,796 Speaker 2: 20 years ago? I don't know. I mean, I guess 641 00:30:11,816 --> 00:30:13,636 Speaker 2: it depends on how you feel, right? But, you know, 642 00:30:13,696 --> 00:30:16,296 Speaker 2: like I think kind of the classic antidote I sometimes 643 00:30:16,316 --> 00:30:19,596 Speaker 2: hear by the aging lifters, right, is like, oh, I 644 00:30:19,636 --> 00:30:21,906 Speaker 2: don't really do the heavy stuff anymore. I kind of 645 00:30:21,926 --> 00:30:24,306 Speaker 2: go in and get more reps and, you know, kind 646 00:30:24,366 --> 00:30:27,486 Speaker 2: of do the higher rep thing. But you can put 647 00:30:27,526 --> 00:30:29,326 Speaker 2: on a lot of muscle mass and be strong, maybe 648 00:30:29,346 --> 00:30:32,346 Speaker 2: not maximally strong, but be very strong by lifting, you know, 649 00:30:32,366 --> 00:30:36,216 Speaker 2: some lighter weights and not crushing your tendons and your ligaments, too. 650 00:30:36,836 --> 00:30:38,876 Speaker 2: And that's sort of what I've gravitated towards as I've 651 00:30:38,896 --> 00:30:41,016 Speaker 2: gotten older. I mean, I'm 39 right now. I'll be 652 00:30:41,016 --> 00:30:43,986 Speaker 2: 40 in March. And, you know, I think about these 653 00:30:44,016 --> 00:30:46,506 Speaker 2: things a little bit, but also it's just I don't know. 654 00:30:46,726 --> 00:30:47,946 Speaker 2: I don't I feel like I don't need to prove 655 00:30:47,966 --> 00:30:49,826 Speaker 2: anything to anybody anymore. You know, as far as like 656 00:30:49,866 --> 00:30:51,406 Speaker 2: how strong I am, that's not really like. 657 00:30:51,746 --> 00:30:54,606 Speaker 1: It's the beauty of getting older. I still want to 658 00:30:54,626 --> 00:30:56,986 Speaker 1: prove more than I want. Yeah. Like you want to 659 00:30:57,046 --> 00:30:58,976 Speaker 1: not care about anything. You want to be a nice 660 00:30:59,026 --> 00:31:01,046 Speaker 1: person and feel like we have nothing to prove in 661 00:31:01,076 --> 00:31:01,856 Speaker 1: the world. Yeah. 662 00:31:01,916 --> 00:31:03,416 Speaker 2: So I definitely don't go to the gym and like 663 00:31:03,436 --> 00:31:05,316 Speaker 2: try to keep up with the younger guys. I'm just like, yeah, 664 00:31:05,336 --> 00:31:07,196 Speaker 2: that's cool, man. Like you guys do your thing. I'm 665 00:31:07,216 --> 00:31:10,336 Speaker 2: going to just kind of try to maintain as best 666 00:31:10,416 --> 00:31:11,076 Speaker 2: I can. Yeah. 667 00:31:18,666 --> 00:31:22,936 Speaker 1: Kevin Murok is an associate professor of nutrition, exercise physiology, 668 00:31:23,096 --> 00:31:27,316 Speaker 1: and medical pharmacology and physiology at the University of Missouri. 669 00:31:28,136 --> 00:31:31,716 Speaker 1: Today's show was produced by Gabriel Hunter Chang, engineered by 670 00:31:31,756 --> 00:31:35,006 Speaker 1: Sarah Bruguier, and our showrunner and editor is Jake Harper. 671 00:31:35,546 --> 00:31:36,266 Speaker 1: I'm Jacob Goldstein.