IRA FLATOW, HOST:
You're listening to SCIENCE FRIDAY. I'm Ira Flatow. Thinking about hitting the gym or going out for a jog this weekend? Well, we all need some kind of motivation to get us going, right? We make the plan. Well, here's a reason to do it, to stick to those plans. Researchers have found that aside from helping us burn calories and shed pounds, exercise changes the DNA, changes the DNA in our muscle fibers, which raises all kinds of questions. Just how do workouts change DNA?
Do we pass on those DNA changes to our offspring? And how do those modifications affect muscle strength and metabolism? Well, here to talk about it is Dr. Juleen Zierath. She is a co-author of the study in the journal Cell Metabolism, and professor of clinical integrative physiology at the Karolinska Institute in Stockholm, Sweden. And she joins us from there. Welcome to SCIENCE FRIDAY.
JULEEN ZIERATH: Well, hi, Ira. Thank you for your interest in our work.
FLATOW: We're very interested, because I don't think anybody has ever given two-minutes thought that exercise changes your DNA.
ZIERATH: Well - all right. Together with Romain Barres at Copenhagen University, we observed changes in DNA methylation in response to exercise. The DNA-code itself didn't change, but the way in which the code was read or the way the DNA was packaged into the cell was changed, because chemical marks from the DNA disappeared. So this changed the perception of other proteins in how they interacted with the DNA.
FLATOW: So the - how the DNA was expressed was changed. Would that be fair?
ZIERATH: Well, not necessarily the DNA. But the DNA is decorated with...
ZIERATH: ...chemical tags. And these are methyl groups, or carbon groups that can be added, or they can disappear to the DNA. And this modifies the way other proteins can interact with the DNA and transmit signals to lead the changes in protein production.
FLATOW: Which is - and which is how your muscles grow if you're exercising.
ZIERATH: Well, that's how your muscles grow. And in this case, what we found was with the exercise, after very strenuous exercise of 20 minutes, we found a disappearance of the chemical tags from the DNA. And what this means is that it allowed other proteins' transcription factors to access the DNA, and this could instruct the cell to make specialized proteins that could support growth and metabolism.
FLATOW: Wow. Does it also explain why you lose your muscle tone if you don't exercise?
ZIERATH: Well, we actually - we didn't study that.
ZIERATH: But you can imagine that if you don't exercise, you might lose it. So we haven't studied that, per se, but we were more interested in how the muscle can store and utilize sugar and fat as energy sources when it's working. And so those were the particular proteins and genes that we were studying.
FLATOW: So lest anybody think that this is a trait like Lamarck thought many years ago, that you're going to pass down the - that your DNA, from usage, has changed and you pass that down to your offspring, that's not what happens here.
ZIERATH: Well, these chemical marks disappeared after exercise...
ZIERATH: ...but within some time into the recovery period, we found that there was a restoration of the marking on the DNA. So we found that it was to be more transient, that you can have a removal of these methyl groups, and that they could really come back onto the DNA after the training. So what we haven't done is to ask whether or not if you, Ira, exercise, your kids are going to have a superb endurance capacity. We haven't studied that in this particular research.
But we've studied the early, immediate changes that the level of the DNA and how other proteins recognize it and how they can regulate the production of specific proteins to support higher growth and the breakdown of sugar and fats with exercise.
FLATOW: Would this also not allow you to study what minimal exercise you need for some sort of change in your muscles?
ZIERATH: Well, we exactly answered that question. So, together with Donal O'Gorman and Brendan Egan at Dublin City University, they have a very elegant exercise protocol. And they bring in healthy volunteers to the lab. They have them do one exercise bout to establish their maximal response. And then they have them come in and do a work bout, which is 40 percent of that max, so it's low intensity, or 80 percent of that max, which is high intensity. And so together with them, we collected little pieces of muscle, and we asked: How much exercise do you really need to see these changes in the DNA methylation?
And we found that 35 minutes of high-intensity exercise was sufficient to have a removal of these methyl groups from the DNA and a production of proteins which would support the metabolism of sugar and fat after exercise. So it's not just to exercise. In this case, you needed to do an exercise bout which would be at the level of where you might not be able to comfortably talk if you're running with a running partner. It's not like walking. Running or biking at a level of exertion where it's hard to carry on a conversation for about 35 minutes.
FLATOW: Very disappointing to a lot of people.
ZIERATH: I know. I know.
(SOUNDBITE OF LAUGHTER)
ZIERATH: But you know, certainly there's a lot of benefits of low-intensity exercise. So I can imagine that if one had a exercise program, adding in a couple of these bouts where you have a more strenuous, you know, bout of exercise, the higher intensity, perhaps twice a week, might be sufficient to support the production of these specialized proteins for glucose and lipid metabolism.
FLATOW: Now let's talk about another part of your study, and that has to do with caffeine.
ZIERATH: Well, that's an interesting concept in itself. So I imagine that people are thinking that if they drink coffee, they won't have to exercise. But that's not really what we showed. So what we did was we used caffeine because biologists for decades have known that caffeine is an agent that releases calcium from calcium-storage sites within muscle cells. So if you bathe a muscles with caffeine, the muscle will start to release calcium. And calcium is an intercellular signaling molecule, and it's one of the early signals that makes a muscle contract.
And so when these muscles were bathed with caffeine, there was a released of this signaling molecule, calcium, and that mimicked - we tricked the muscles into thinking they were exercised. So that caffeine release mimicked the exercise response, and there was a disappearance of these methyl groups and an increase in the expression of genes and proteins that supported glucose and lipid metabolism.
FLATOW: So basically you're saying you got the same result using just - bathing the cells in caffeine as you did in exercising?
ZIERATH: That's right, tricking the muscles to think they were exercising was sufficient, and that implicated that there were some signal inside the cell, and that might be related to this calcium released that was important for instructing the cell to reprogram itself.
FLATOW: You know the next question, right?
ZIERATH: Oh, should you just drink coffee?
(SOUNDBITE OF LAUGHTER)
FLATOW: I don't even have to sit here. Yes. Absolutely.
ZIERATH: The amount of coffee that you might need to drink is somewhere between 50 and 100 cups per day. It's a lot, depending upon the, you know, if you have a store, a big latte, you know, or a little espresso, you know. But you need to have pharmacological doses of caffeine, and you'd probably end up with sweats, heart palpitations. You know, there's a lot of negative effects of too much caffeine. So I hate to tell you this, but I think you're going to have to exercise for 35 minutes at 80 percent of the maximal dose.
FLATOW: Yeah. And I guess being on that treadmill with a cup of coffee is not going to do much.
ZIERATH: Well, you know, we'll see. I mean the next study would be to ask if there's a synergistic effect. I mean, if you drink, you know, what you're saying, drink a little coffee while you exercise, is it helping you? But I think for the time being, perhaps exercise might be the answer.
FLATOW: Where do you go with your studies from here? What else would you like to know?
ZIERATH: Well, you know, you kind of brought this up earlier. And one of the things we're really thinking about is whether or not any of these effects could be transferred to the next generation, and so that's one of the questions we'll try to answer. And the other is, what other nutrients or lifestyle modifications could change the chemical tagging(ph) on the DNA, this DNA methylation?
So we have published a study earlier that people with diabetes, Type 2 diabetes, they have sort of the opposite effect with exercise. They have too many of these methyl groups, and they have a reduced expression of these proteins, and they have a worsening of their metabolic phenotype.
So the idea would be that if we could take diabetic patients, have them come in and exercise, would the exercise be sufficient for them to restore the specialized proteins that can burn fat and glucose and help them with their metabolic control?
FLATOW: And how would you test whether it can be transferred to the next generation? I have visions of my own, but I want to know if they match...
ZIERATH: Yeah. Yeah. Well, obviously, to do that study, you know, in my offspring or your offspring, we'd have to wait quite a long time. So one way to do that is to, you know, to take animal models. And you can do work performance tests in animals, and you could study their running capacity or their performance capacity and measure some of their DNA methylation, and then ask if their offspring has also received the benefit of an exercise, life-time exercise program throughout.
FLATOW: You mean it would be transferred to their sperm or their...
ZIERATH: It could be, yeah. I mean certainly that's something that we're looking at, is, you know, Romain has done an outstanding study where he studied rodents, and he studied male rats who received a high-fat diet, and he studied the offspring. So the mother was on a regular diet, and the father was on a high-fat diet. The father was fat and had signs of diabetes. And the offspring of that pair - the female offspring looked more like the father. And so the father could transfer some signals to the daughter, and it wasn't through changing the DNA code. That was changing some of the methylations. So we'd like to apply some of that work to exercise.
FLATOW: So this is - this means that it's being changed all throughout the body, or is it just in the part that's being exercised?
ZIERATH: Well, you know, that's also a really important question to resolve. So you know, when you exercise, many organs are involved. So you're, you know, you've got your fat cells involved, you've got your livers there. It's pumping out a little bit of glucose as you run along. So we're doing some studies now with a surgeon, Erik Naslund, and we've been able to get little pieces of liver and fat and muscle, and we've been able to ask whether or not there's tissue-specific changes in DNA methylation. In this case it's with individuals who are severely obese and then asking whether or not weight loss in severely obese people is sufficient to normalize the DNA methylation marks.
FLATOW: Wow. Very interesting stuff. Good questions, Dr. Zierath, and we'll have you back when you answer some of them, OK?
ZIERATH: Sure. OK.
FLATOW: All right. Dr. Juleen Zierath was co-author of this study in the journal Cell Metabolism. She's a professor of Clinical Integrative Physiology at the Karolinska Institute in Stockholm. Thanks for staying up late for us today.
ZIERATH: All right. Well, take care.
FLATOW: You too. Have a good weekend.
ZIERATH: Be sure you exercise now, Ira.
FLATOW: Absolutely. Going to try the coffee too. Stay with us. We're going to be switching gears now. I'm Ira Flatow. This is SCIENCE FRIDAY from NPR.
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