There is strong evidence that exercise is wildly beneficial. There is even stronger evidence that most people hate to exercise. So if a pill could mimic the effects of working out, why wouldn’t we want to take it?
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among the most popular resolutions. We make and fail to keep exercise this is the year. I'm really truly going to do a whole regular exercise thing. If that your resolution, you should find today's up so particular compelling it was first published last June. and has already been downloaded at two point. Two million times it is called, the zero minute work out, faster Stephen, Pay Stephen them the gym heart rate is one hundred and ten you're talking rate is one hundred and thirty beats per minute. We all know the exercise is good for us. We also know them. People don't get nearly enough. Thirty, four percent of U S. Adults are physically inactive. Another twenty percent
are insufficiently active and not surprisingly, almost forty, of. U S. Adults are classified as obese to be reductive. Many of us eat too much an exercise to it. Why don't we get more exercise? Its be honest, it is hard work. I told you to faster the cost of physical, activity is massive, not just an illness and death in dollars to researchers, the centre for Disease control every university to the? U s about a hundred seventeen billion dollars a year and healthcare Due to inadequate physical activity and those are just a direct costs treating cardiovascular disease diabetes and so on, doesn't even include things like the loss of productivity. Are you ready it strange if you think about it,
thousands and thousands of years. Our ancestors worried about not getting enough food to eat in their daily life required physical activity. Today, food is everywhere and cheap and super. At in a lot of us have lived that require very little physical activity, which is why I am here on the stupid by I'm going to take that personally, let us people who spent a time and effort trying to get the exercise more mostly they failed. So what happens next? Would it be amazing if instead, the exercise there was some MIKE Pooh like that idea? I do not like that idea wanted I'm happy
from stature and Gunnar productions. This is frequently radio casket explores the inside of everything. Here's your home Steve Indefinite, ok, glad that's over, so obesity started out as a problem in wealthier countries, but now it spread to middle in low income countries. The contributing factors are not in dispute
consume too many calories, especially low quality calories, and we don't burn off nearly enough calories with physical activity now to be fair. Burning. Calories through exercise is a pretty inefficient process. It takes a lot more exercise and you think to burn off one cheeseburger in that regard. It be better to just eat less that said, exercise is also considered a very valuable input for overall health that's what we ve been told, at least, but does not take that for granted. Let's see if we can find real evidence for that claim, and why exercise is must be so good for us, we'll start with this man. My name is Michael Joiner and I'm a physician scientists at the meal clinic a physician scientist meaning what I'm, basically a physiologist, whose also clinical immissio? That sounds pretty impressive. Physician scientist at the male clinic, but you see,
Michael Joiner was an unimpressive student growing up in Arizona York. that was a sort of an indifferent student at Rincon High School, and I started college in nineteen. Seventy six and went to several schools in one year I ended up in nineteen. Seventy seven. At the University of Arizona where he promptly almost flunked out. in December of nineteen. Seventy seven I'd actually signed up to take the tested should become a to Sun city. Firemen. And what happens I was out running a race. Ten carries joiner was a pretty good athlete thy ran track, field at the University of Arizona where I ran the five thousand to ten thousand also ran a two hundred and twenty five marathon in the late 70s. If you're not familiar with marathon times two hours and twenty five minutes for more than twenty six miles a very fast time, and then I continued drone tat was about forty. He still exercises about an hour a day. It varies between
a relatively easy day of of aerobic exercise on the bike, or maybe some swimming and in Hungary the opposite days. I do something relatively tents, which includes a warm up and then about thirty or forty minutes of circuit training and because I'm sixty years old I've done probably a little bit more strength, training the last five ten years because, as you get older, Are you really want to avoid frailty muscle loss? slip on the ice, said sort of thing back when Joiner, thinking about becoming a fireman, and He was running that ten race, the meaning be coil whose a well known exercise physiologist, and he was a graduate student in the lab Tucson at the time. And he said you wanna be a subject in a study on lacked a gas it It sounds good to me so I showed up and ran in the lab, and I said man. This is unbelievable. There's actually people who do this for a living Joyner was told he
that. Work in the lab is a student assistant. If he got his grades up when so, then I had kind of a square wave experience with my grades and sorry, basically getting straight ace. I saw that if you wanted to do studies in humans, where you put catheters in new biopsies he's net sort of thing would be facilitated. If you were a physician, so unlike a lot of physicians, who get interested in research in medical school as an aside fellowship, I actually went to medical school with the express purpose of becoming a research based integrated Is it did take joint or a while to get into medical school? Because the kind of dual academic rehab to make up for this first, two bad two years and I came to mail and nineteen. Eighty seven and I've been here ever since so you're a big deal in the field of physiology exercise. Physiology. Can you first just for total. Lay people define physiology for us if you think about anatomy, anatomy describes the parts of the body Physiology
really the engineering equivalent. That says what are these different parts due warning in combination, and so there are all sorts of regulatory mechanisms increase or decrease our breathing increase or Greece, our yearn output and so what we whose physiologist study these regulatory systems and try to understand how hall living for damned environmental challenges. Ok, so open ended question. Tell us what we know in a nutshell, we'll get into details as we go, but tell us what we know about the benefits of physical exercise What we know in a nutshell is that people were physically active, especially if they give somewhere between hundred fifty three hundred Its per week of moderately vigorous physical activity have a large reduction in their all cause. Mortality, typically about a fifty percent, or maybe forty percent reduction in their all cause. Mortality
And typically, they live somewhere depend on the study between about four and seven years longer quickly, define me all cause mortality. It just me You could dive anything, could be cancer, heart disease, infectious disease and so forth, and One of the points people you remember, we typically think of exercises being especially protective against death civility and diseases associated with the cardiovascular system, but it's also protective against a number of forms of cancer and a number of things like diabetes in others. Jesus. Ok, so you may be saved yourself, Michael Joiner sounds credible and he's got great credentials, but we also know he's a bit of an exercise fanatic himself. So how can we be sure that its exercise, its actually causing better health outcomes? What sort of baseline physiological evidence is there for that claim? Will a couple things that you are the best evidence comes from varies
population cohorts, most famous mean the bus driver, bus conductor, data from Africa or two in London, where they showed the sedentary bus drivers had much higher rates, Corner Ardor Disease and heart attack and the active conductors who were walking around punching tickets going up and down the stairs all day. Any showed a similar thing when they compared clerical workers to Postman again, all else, all members, the british civil servants and that's where that NEO forty fifty percent reduction, all cause mortality and cardiovascular mortality came from ok. That is a neat. story the bus drivers, but that was a long time ago has fact been shown more recently been shown. over and over again and every sort of cohort study. Then you come to some other things. So if you start looking at people were the risk factors, people, hypertension, high cholesterol, obesity, so forth, and so on people with high levels of physical activity or Cartier spirit.
Fitness. Their risk is markedly blunted. So I like to tell people that exercise and fitness absolve you of other sort of risk factors since all right, fine, but a couple of things here, cohort studies or population studies Those are not the randomized controlled trials that scientists consider their gold standard, and how do we know that people with high levels of physical activity has Joyner's describing here? How do we know that there aren't other reasons for their good health may be. The kind of people were more likely to exercise are the same people who are more likely to eat better, were sleep better, maybe they're the same people who don't smoke or who face less stress in their lives. Stressors like poverty or differ work or home environments? How does joiner know that exercise is such a strong causal mechanism of good health, you get into studies in individual humans, where you can take people.
Do very brief periods of exercise, training, improve their glucose tolerance, improve the function of the blood vessels and prove a whole lot of biomarkers, which are associated with her. And then you go one step further to animal studies, and you can really take a deep dive into the mechanisms behind those positive changes. Okay, what are those mechanisms? A lot of joiners research is about how physical activity increases blood flow to skeletal muscles. Her hurried goes from steer. Seventy two around two hundred save about a threefold increase in heart rate and in the meantime, blood pumped with each heart. Beak also goes up so think about that at rest- a tiny amount that blood flow. Maybe five hundred emails is going to all the muscle in your body during maximum exercise. Perhaps sixteen or seventeen leaders is going to muscle. Now. Why is blood flow per se important or beneficial
Well that the bottom line is if you're gonna do prolonged exercise, you ve got to get out, from the lungs to the skeletal muscle she had ever been cardiac output any evening, got gotta get it the muscles that are actually contracting. So it's just a supplied in situation. Ok, so take me from there. So you do vigorous exercise. It increases the blood flow alot. What then are the longer term. I guess physical and cognitive benefits of that increase blood flow. One is that the blood vessels kind of growth They become larger in diameter. The lining of the blood vessels to ask for the failure becomes more slippery and becomes more prone to relax. Verses constrict, which makes your blood pressure lower and in the capillaries lorries in small, I'd. Vessels around the skeletal muscles also grow so because there is a large increase in cardiac but all of the large blood vessels throughout the body become law and in the end, a function increases
become more elastic, less stiff, which is also a good thing. The thing to remember is- and this is a really big finding the last twenty years is it. There are almost like substances secreted by the skull Muscle which have remote effects have effects on the liver, timber metabolism, never on blood vessels everywhere, and So really something called beady enough. Rain derived Neuro Trophic factor, which is good for brain growth in people think that's at least one of the links between our physical activity and cognition and preservation of cognition as you age. So it sounds like the benefits of exercise are massive and widespread and therefore we would all be idiot to not do a lot of exercise, or at least enough exercise, so doktor joiner. What share of Americans do get what you consider to be enough exercise? Oh, you see various
members depend on where survey researcher tracking research, but you know if it's twenty percent, that's a generous number. So do you feel that you personally have been? reaching the gospel of exercise for a long time and that people are not really buying. You know, I just tried a point, the benefits and set a good example and be as in people as I possibly can. People really need to understand that they need to do something. Do it regularly and it's ok to take it at small bites, but, until we have a wholesale change and in transportation and food policy and just the way things are, I don't see a whole lot changing most of the populations behalf. Your lines with various overdid covert incentives, and I think we You have a whole lot of incentives to be physically inactive needler that mean there's a terrific
but he from Toronto showing that they walk ability of whatever blip coded equivalent urine in Toronto. The walk ability of that neighbourhood had predicted who gained how much weight over me ten or twenty years time that we have built environment problem. We got an incentive problem. I think that come in as much as I'd like I want to exercise. I think we ve also got here transportation policy problem when you go to places like the Netherlands or Denmark with it, are very biking friendly when whole cities are built to do that. You see a lot of really fit people the chance Jeez we're endlessly pitted against the technological advances in civilization. That tends to make us not move. That's Ronald Evans. I am the director of the gene expression. Laboratory at sock ensued
Institute for biological studies is one of the most important biomedical research institutes in the world and a lot of the work that we do. Studies the nature of genetic circuits. The control metabolism. Doctor Evans, like Dr Joiner, is a big believer in the benefits of exercise. Exercise is a beneficial factor that burns calories, but it also activates many metabolic pathways is Prohealth, but Evans is also a realist, and this, given the human propensity to eat too much and exercise to little, has turned Evans into a futurist. He wonders whether we should accept the fact that most people are never going to exercise enough and instead think of a biomedical solution, very big question, and I think it deserves a lot of thought
court of solution is Evans, working on exercise in a pill, details coming up right after this Fr Radio sponsored by capital, one with no fee. is or minimums on checking and savings accounts. Banking with capital, What is the easiest decision in the history of decisions, like choosing to listen to another episode of your favorite podcast and with their top rated app. You can deposit x and transfer money anytime anywhere, making capital one and even easier decision. That's banking re, imagine What's in your wallet terms, apply capital, one a member of the icy
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women would do well to exercise more than they do fact to public health advocates, and others have been urging us to exercise for many years fact. Three, their urging doesnt seem to work, consider fact for, in the U S more than eighty percent of large companies offer programmes that encourage and often incentivize exercise in weak control, random, I study of one such company, PJ's wholesale club, was recently published. In the Journal of the American Medical Association. It found that ways in the wellness programme did self report that they were more. Likely to exercise and manage their weight. But the data the old. There were no significant differences in actual health markers, including weight loss
and as we heard on an earlier episode of requirements, radio, a world class team of behavioral scientists recently didn't experiment over twenty eight days. Fifty three different interventions to try to increase the exercise activity of people who are already members of a gym. So after our twenty day programme. Pretty much. We saw nothing in terms of behavior change, its Katy milkman from Pennsylvania all fifty three the programme. Pretty much nothing sticks, and that was the ultimate goals, allows major failure with so much oh, you can understand why a lot of people look for exercise shortcuts revolutionary transform system is the safe, active and affordable way to change the way you work out and look forever, but me there's another kind of Georgia, something a bit less hawks, Trish a bit more grounded in science, which brings us back to the biologists, Ronald Evan
from the Salk Institute. Evans is well known in the field for having discovered a family of hormone receptors that act as genetic switches and, if you think of genes as instruments in an orchestra, you can have many different kinds of songs or many different ways to have them work together. And the conductor that makes the genes come on at the right time and orchestrate all that our regulatory factors that are called transcription factors that activate the gene, so those are genetic switches, this is really the underpinning of a lot of our bodies. Physiology is, while all cells of the same number and same set of genes? Visual cells activate different sets of genes and the reception
there is in the hormones, Control Jean Networks, and so a lot of our physiology is about genetic control. The discovery and understanding of this mechanism of genetic control has been incredibly important. Once you have a mechanism, then you can think of had actually develop therapies, her drugs to control that mechanism everyone's familiar with hormone replacement for people. Sometimes you lose at thy gland for various reasons, and you can replace that by finding or making the hormone and then giving back to the person. The staring hormones are amongst the most widely prescribed drugs on the planet and perhaps the most famous steroids hormone therapy, the birth control pill, and that's all about you,
these receptors and in many ways the impact of this family of receptors and pharmaceuticals, have changed society Ronald since maybe on his way to creating a new pill which once again, has the potential to change society exercise in a pill. His lab is developing a pill that would mimic the effects of exercise in the Alps of actual exercise. Other labs around the world are working on similar exercise medics as their called with various mechanisms. Evans's pill work, by targeting one of two key hormone receptors. There are two hormone receptors that we discovered there very, very close to each other, but play exactly opposite roles and complementary roles. embody physiology and as wells and disease, and so one of the hormone receptors is called, people are gamma and it
is the master regulator of adipose tissue adipose tissue is what most of us know as fat. You need this genetic regulator to activate the fat network. It's critical for survival. You need to store energy and fat to survive, and then the partner for that that's called Ppr Delta, which we discovered in nineteen. Ninety five: that's the receptor that burns- and most of the problem with disease is too much storage and none of burning. So one of the ways that we have approached the problem is looking at drugs to be specifically built to target these fat burning, receptor, ppm delta and that's lead to number of companies producing new kinds of molecules, and the companies that I created
a number of years ago develop a screen technology that was licence to Glaxo. Welcome they built a drug called cheetah view. Fifteen. Sixteen Glaxo welcome is now known as Glaxosmithkline G W fifteen. sixteen originally had a different purpose. It was made it change cholesterol levels and to try to increase something called html. This drug never made it into after approval. It had problems problems like causing tumors in the mice. It was tat. On Evans eventually began working with a less powerful version of the drug, with the assumption it would be less toxic. Another difference. He wasn't looking at its effect on cholesterol, so one the surprising things that come out of the g for Fit
sixteen compound and was very dramatic result is when we gave it to sedentary mice or obese sedentary mice, either one for about thirty days. The G W drug progressively act they the genetic programme it is normally activated by exercise. I think we should hear that last bit again. The G W drug progressively activate the genetic programme, it is normally activated by exercise. In other words, there physiology seem to indicate the mice had been exercising, but these mice we're not getting exercise. There were just getting the pill, as you can imagine. This was a pretty exciting research results, but how well did the pill do in terms of giving the benefits of exercise in a general sense? You have to be careful when you say: does the pill give the benefits of extra
as in the general sense, because exercise is a hundred things, but I should say in general exercise, no matter how you do it focuses on You things it increases energy expenditure, it tends to increase burning of lipids and fats and sugars, you get adult Neuro Genesis and that enhances the cognitive performance and also improves immune fitness lowers inflammation as many benefits to the heart and other parts of the body. Now we go to this, what is people are a delta drug do in terms of metabolic fitness in and lets, say the brain. It does exactly same things. It gives you this increase energy expenditure, you burn more lipids, you burn worship,
you're a new correct year in Southern Europe. Adipose depot starts to shrink, so you lose weight and the drug by itself gives you adult Neuro Genesis. The drug also seemed to boost endurance, at least in the mice. After thirty days of giving them the drug Evans and his team put the sedentary mice and a treadmill, it's a mouse treadmill very cute, and we compared the mice that got the drawing with ones did not get the drug and the difference was striking. The ones that got the drug could run approximately one hour longer continuous running than ones that didn't, is the mechanism for this insurance effect? What the actual drug does it increases fat burning by the powerhouse of them? wholesale, which called the Might of Congo and the mighty
Recombine, sugar, a fat, but what the drug says is we want the mitochondria to burn fat specifically and convert fat into the chemical form of Energy called ATP, but dont burnt sugar. That's because the sugar or glucose is needed for in energy and so the Pieper Delta drug powers, the brain and powers, the fat. By separating out the who energetic molecules in the body for different purposes. One. the muscle and one for the brain, and by doing that, you're able to sustain you're running time by an hour or an hour and a half the bureau so the sounds pretty much like a miracle drug as in others
so too, right before the two thousand, eight Beijing Olympics Evans reached out to the world Anti doping agency, her wada, about the potential for athlete abuse and eventually help develop a test for it sooner: Wada banned the drug, but into doesn't thirteen a bunch of pro cyclists were caught using it fast forward today Run Evans and pharmaceutical firm. He cofounded might a bridge working on a new form of the drug. That's meant to minimize side effects, so the mighty bridge drug has been in what's called phase one studies now moving on to face two studies, so the most critical is the is one to me because that's the safety there now through that part, so the next part is: does it work than works very well in the mouse models, but we have to show that it works well people we know it's safe in people, but we have now
show that it works. I would say two or three years that we will have a pretty good idea if it's working Human disease in a way that could achieve FDA approval together, drug through FDA approval, might bring is targeting patients with due Shane muscular dystrophy. That's a genetic disorder, typically striking young boys who rarely survive into their twenties. There is no real drugs to treat it, but our approach is to restore this balance. Of energy utilization in the muscle, and we can stimulate that muscle to actually burn fat and become activated as if it was being exercised. But Evans clearly sees a mud wider potential use for this drug. There is absolutely no way that the petty she'll here is gonna be limited to one or two diseases. It will be very high from men about
to Neuro to Basque were to aging we can think of the potential here in different ways: and maybe to the wider question, can be used. Preventive. We in some cases, just to maintain health, is opposed. It just train disease. and this is not an easy issue because taking healthy people in giving them a drug is not common. Now it does happen. The lot of people take adult aspirin from their entire life because its thought to be helpful to reduce formation and reduce heart disease. Tens of millions of Americans also take satins every day to forestall heart disease millions more take met, foreman to treat diabetes or even the onset of diabetes. We put fluoride in our water supply to prevent tooth decay in Could you transition is to a society that is getting heavier,
running into the problem of obesity, diabetes and the related complications. The answer is yes, but I think a social and ethical component, your a big question, that, should be addressed and is not unusual for scientific advances to raise social issues and questions. We have this the time indeed, just because a drug may soon exists that could mimic the effective. Size does not necessarily mean we should immediately spike our water supply with it, so Evans's drug, if it does make it through FDA, provoke, will surely have its philosophical and Ethical sceptics, but even now it's got its physiological sceptics an exercise mimetic that again is Michael we know from the male clinic, if you think about the main ones have been designed to try to increase. function of the mighty country a little
Nelson, skeletal muscle that that burn carbohydrate fat and are critical to the metabolic benefits of exercise and Certainly, you can stimulate those with with drugs, but if you look at the broad class of things, it acts Thyssen does it goes way beyond just affecting the mitochondria effects. Again, a blood vessels in the remote effects of training, the effects on the brain facts on intermediate metabolism, in all sorts of other things. So I think you can find mimetic for things that sort of look like exercise, but I dont think you're gonna find the big picture. Trucker comp they can do. The ten or fifteen main things at exercise does for people. What would you think of? Let's call it the exercise, farmers
did you call that works along lines, you're describing they're, gonna, mitochondrial level for those who can't exercised you? Do that's a physical handicap or some other conditions. You like that idea. Absolutely absolutely you re start thinking about exercise is good for your lipids. size is good for diabetes, exercise good for this net and others. A terrific I yeah and very interesting paper in the early two, thousands and believe in the British Medical Journal which said, you know why don't we put everybody a load of status, Lotos Hannah, hypertensive everywhere fifty logos and I diabetic drugs, and see what it would do to their their life expectancy in all cause mortality. So some people have argued that really. This is closer to an exercise. Mimetic then, drugs a target- the mighty country, for example, but you can imagine that if a so called exercise pill does come to market, it may provide people the licence never exercise again, there's been
search showing that there can be licensing effects with diet. Behaviors. Your your mind me that that I've been done. Well, then I may be eat more Katy milkman again from the University of Pennsylvania. So if you give people up, oh and say you know this has the effect of exercise. Will they feel licensed not to exercise its a real risk? I do not actually like to think of it. way because we are designed to move, and that again is Ronald Evans. The man behind the exercise pill, and so the socialist, Who is not just should we give the drugged? Everyone is How do we manage the intrinsic advances that are working against our health? He may not intend for it to replace fitness, but will people take it and then feel that their life, Instead skip worked out, and so whether that's the intent of the medication doesn't mean, I won't be a nasty side effect Marcus, Barman physiologist.
University of Alabama Birmingham is also not in favour of an exercise bill. Because there are thousands upon thousands of molecular responses. Exercise that cannot be recapitulated by one pill. Batman has another idea, a sort of hybrid idea which he feels may be necessary, given the guilty of turning and inactive person into an active one, going from trousseau Terry status to a regular exercise, training, habit or behaviour. There are a lot steps required to make that happen in one of those. I think that would be very tangible, for people is a prescription with good guidance, a precise meaning, an individualised exercise. Regimen. It really doesn't do do the patient lot of of good for health care provider. To just say why your boy pressures,
the glucose is high and you need loosened weight, so you should do more exercise. They don't know how frequent what intensity, what doze Is it resistances endured? Is it a combination, famine and his research team at you? A bee have been doing research for fifteen years on this idea. They started with older adults and now work specifically on patients with Parkinson's, multiple sclerosis and epilepsy, but their ideas at everybody could benefit from an exercise prescription. Let's just take the individual who comes to the clinic forty five years old, they gotta body index of thirty two for the record. That is a pretty high, be am I the equivalent of a fight, Put ten person who ways more than two hundred and twenty pounds they ve got some level of income resistance going on, they ve got a stage. One hypertension they ve got some need pain in a perfect world, or at least in Marcus bombing,
world. A physician would have a lot of good data on exactly what forms of exercise at what intensity and duration would be most useful. If you can then point to that data and say to that person, the evidence is clear this works, and now I am going to refer you to somebody who knows how to implement this evidence based proscription I, that would have a major impact on were not somebody adopts a change, but the truth is those data on element. Specific exercise are fairly sparse in terms of which type of exercise is best for a given disease risk cluster? The research really void in many areas that may be starting to change. The national Institutes of Health is starting an exercise trial as part of a pre ram called the molecular transducers of physical activity consortium and that stuff, he is really comparing resistance. Training
during training and true, to understand the mole accurate mechanisms by which each of those modes of exercise training induces potential health benefits. You could also mention that technology, especially sir technology has a larger role to play in helping to achieve our fitness schools, lake, making, exercise, equipment and apt that, rather than beating us up Stephen, I told you to peddle faster or a bit more encouraging. Well, aren't you the little champion five comments on the back without a break? That's your new personal vast! In the meantime, come get next week on frickin, I'm radio. We all love to read about the latest breakthrough in psychology research. Don't we but the day I think, is quite right, which is that we can very easily push our wonder buttons and and pusher interests buttons using pseudo, rather science. What if I
told you that a the terms that psychologists use bar all different kinds of wrong inaccurate or misleading, frequently misused and big was terms oxymorons and pleonasm, for instance. So one that comes to mind is by stander apathy. The biggest We're ready to assume that these personality traits are unitary. They only have one cause and that their inherited one of the most Portland several in neuroscience of the last few years has been that all that hardwired stuff is completely wrong. What are psychologist good for anyway? That's that's, not a backlash. misused and abused concepts from psychology psychiatry its next time on Friggin Amis radio for clemency, radio is produced by sticker and W productions
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Transcript generated on 2021-01-18.