The Rejuvenating Effects of Exercise

Hardin Young: Welcome to Short Talks from the Hill, a research podcast from the University of Arkansas. My name is Hardin Young and I’m a writer here at the university. Today I’d like to welcome Kevin Murach, an assistant professor in the department of Health, Human Performance and Recreation. Murach’s research broadly pertains to adult skeletal muscle mass regulation in the context of exercise, aging and beyond.  Less than year into his first tenure track position, Murach’s work has been featured in The New York Times, The Scientist, Discover, Men’s Health, and Runner’s World. Kevin Murach, welcome to Short Talks.

Kevin Murach: Yeah, thanks for having me. It’s pleasure to be here.

HY: First, I want to ask you about your PhD. It’s in human bioenergetics. I’ve never heard of that. Can you explain what that is?

KM: I don’t know if I can, actually, to be perfectly honest with you. You know, essentially that degree – the Human Performance Laboratory at Ball State University is where I got my PhD and that’s the longest running human performance laboratory in America. And it really had a focus on skeletal muscle function and exercise physiology, so I guess human bioenergetics in that context could be considered the confluence of those things. It’s basically just trying to understand how to improve human performance – whether that’s exercise performance or performance with aging. You know, improving dysfunction with aging through exercise, and so that’s, I guess, kind of the way that I define it. It’s a fancy title for sure, but in essence, though, I studied muscle mass regulation and how to improve muscle performance.

HY: How did you get interested in this field of study?

KM: Great question! You know, I was an athlete growing up. Not a very good one, but I liked to, you know — I played soccer. I played a little bit of basketball, some tennis and then I started lifting weights when I was in high school. How the muscle adapts to different types of stimulus and to different training regimes kind of captured my imagination. When I start lifting weights, you know, muscles started getting bigger and I was like ‘how does that go?’ You know, like what’s causing that exactly? So I started reading magazines, Men’s Health, these different things, and those aren’t the best resources necessarily, but for certain things it’s fine, but for other things not so much. But the process, the scientific, you know, things that happen, the biological processes that happen in the muscle are kind of really what captured my imagination. And then I got to college and I took an anatomy class and started to understand more about muscle biology through that and then, you know, chose exercise science as my major in college. And that was the springboard on which my academic interest in skeletal muscles took off. And one thing leads to another – you get a master’s degree in a related topic. You get a PhD. You go and do a post doc for a number of years and you just kind of become more and more granular over time, until eventually you’re studying like 1 cell type and one gene or whatever the case may be. But, yeah, it kind of started just as a recreational interest that turned into an intellectual passion.

HY: I know aging is important to what you’re researching. Is there any particular reason you moved into that?

KM: Yeah, aging affects everybody, right? And it’s interesting to study diseases. It’s interesting to study different conditions, interesting to study athletes, of course, but at the end of the day, we don’t know how to solve aging. Like everybody goes through it. Everybody dies. And we’re not trying to, you know – I’m not super interested in extending lifespan per se. But I am interested in trying to improve people’s lives and make them healthier for longer. And I think improving muscle health is a big component of that, and that was kind of my motivation. You know, what’s the greatest benefit and impact I can have on society through my research? And aging seemed like a pretty obvious target. Also I mean I’m still relatively young, but I am getting older and I am noticing things aren’t functioning the same as they used to after exercise with respect to my adaptation and my recovery. That process and how that’s being disturbed is interesting to me, and maybe there’s something that I can do through my research that can help to, you know, improve my own performance in some ways. And so I guess those are sort of the things that kind of drove me into that field. I study a lot of different things, but aging is definitely one of my major foci right now.

HY: OK, that kind of sets up my next question because you recently co-authored a paper that pointed to what you described as the rejuvenating effects of exercise. Can you give us an overview of the work involved and specifically what your role in that research was?

KM: Sure, well this project was a nice collaboration between the University of Kentucky Center for Muscle Biology, which is where I did my postdoc and where most of the experiments actually occurred, and the University of Texas medical branch. I have some great collaborators there — Chris Fry, Stan Watowich, Yuan Wen, Andrea Dimet-Wiley — we all got together on this project and it was very collaborative. The question really was: if you exercise late in life what are the potential benefits of that and how much can we turn back the quote-unquote “aging clock,” specifically, in skeletal muscle? So we had to develop a mouse model to answer this question and my colleague at Kentucky, Corey Dungan, developed this mouse exercise model and it was called PoWeR — progressive weighted wheel running, PoWeR’s the acronym — and we wanted to leverage that in older mice just to exercise mice towards the end of their life. And kind of use some biomarkers to get an idea of whether or not the aging clock was kind of being reversed in the skeletal muscle. We know that exercise, at any point in your lifespan, has you know, myriad benefits and we wanted to kind of drill down into something called epigenetics, though, which is essentially how gene expression is controlled. We all have these different genes in our DNA and how they actually get expressed, how the genes get turned on and off is condition dependent. And we wanted to drill down into — OK, are there these epigenetic changes that happen in late life exercise that could potentially be reflective of a younger skeletal muscle phenotype? So that was the question that was driving the research. So we got together – all my collaborators – we exercised some aged mice, and then we use these epigenetic biomarkers to try and capture whether or not the aging process is being kind of slowed down or reversed at this level of epigenetics. And that’s kind of what we found with the paper that we ended up publishing. It seemed like, at least with that kind of exercise in those mice, there was a sort of a quasi anti-aging effect that was occurring at the epigenetic level with just, you know, eight weeks of exercise training in the mice, which, it’s important to note that a mouse is life span is like two years and so as far as the relative amount of exercise, I mean, it’s probably more like prolonged exercise in humans. But nevertheless, there seemed to be somewhat of an aging mitigation effect at the epigenetic level.  We were the first ones to kind of show that using this specific tool that looks at aging specifically at the level of DNA methylation, which is an epigenetic mark.

HY: And your specific role in this paper was what? Because I know that you’d mentioned in a previous conversation that a lot of the mouse work was done in Kentucky, but you have a Molecular Muscle Mass Regulation lab here, where you do work. So what’s your end of this paper specifically, if you can explain?

KM: Yeah, well I wrote up the manuscript. I interpreted the data. I made the figures. Basically, I kind of put it all together. You know, a lot of the experiments, like I said, happened at Kentucky with my collaborators. But you know, Yuan Wen was our bioinformatics person and he was a co first author on this paper. Andrea Dimet-Wiley coordinated the project and she was a big part of putting everything together. But I ultimately took the helm and kind of finalized everything, put it all together and sort of made sense about all the data because it was a lot of data. It was a lot of data in a short paper, and so you know a lot of — omics data is what they call it. So there’s various omics datasets that we had to compile and put together and kind of make sense of what was going on and I did a lot of that work.

HY: You also co-authored another paper that showed that muscle retains a cellular memory of prior training. And I know you’ve got about several other papers you put out recently – but one thing I think that people are going to be wondering about is do either or any of these papers tell us anything about the kind of exercise that we should be doing or how often we should be doing it?

KM: Sure, yeah, I mean the truth is that the exercise model we use in mice is a unique model. The problem with exercise training mice is that they’re difficult to exercise train. They’re not just going to, you know — you can’t set up a little gym in their cage and they’ll just go periodically to lift weights or anything like that. So we have to get creative and so the exercise model — typically what we would do is a surgical technique to stress the muscle in a way that was kind of akin to resistance training. But it is still very different. I mean, we don’t cut muscles out in order to get other muscles to adapt in humans, that’s not what we do. We go to the gym. We exercise. So the model we developed was this high volume resistance training. I think the closest analogue to it in humans could perhaps be something like concurrent training — so maybe something like CrossFit where you’re combining modalities — endurance and resistance together. Perhaps it’s like heavy cycling for your quadriceps or maybe like if you were a military person you were walking really long distances carrying a pack, maybe something like that. There’s not a really a quite a direct analogue but the adaptations that we see in the muscle are very similar to types of things we see with like something like CrossFit, where the muscle gets stronger but more fatigue resistant. But really we kind of generate – I guess an athlete. It’s sort of like an athlete phenotype that we see in these mice, and so as far as the exercise prescription goes, I mean, I wouldn’t necessarily recommend to somebody that they put a backpack on and run 10 to 12 kilometer’s a night. That’s not necessarily what we’re saying, but I think it does say something about consistency. I mean, these mice were exercising every day. And I mean as you get older you need more rest in between exercise bouts in order to recover. But it does say something about being consistent and I think it does say something about doing endurance and resistance training and how good that can be for you instead of just doing one modality. I mean, I personally do both. I exercise almost every day and every other day is either resistance or kind of a cross training, endurance type of thing. And I think it’s just important to – you want to walk into the later stages of your life with as much muscle mass as possible because you’re going to end up losing it. That’s called sarcopenia. But you also want to focus on your heart and I think all these systems are definitely integrated, so having good cardiovascular health can be good for your muscle health and vice versa. And so I think it does tell something about that ass well, but again, as far as being a direct analog, you know, between the mouse exercise, there isn’t one. But I mean it definitely says something about being consistent with your exercise and the benefits of combining modalities.

HY: Kevin Murach, thank you for joining us on Short Talks.

KM: Yeah, yeah, yeah, thanks for having me. This is a lot of fun, I appreciate it.

HY: You betcha.

Matt McGowan: Music for Short Talks from the Hill was written and performed by local musician Ben Harris. For more information and additional podcasts, visit Arkansas Research. That’s arkansasresearch.uark.edu, the home of science and research news at the University of Arkansas.