 We're back. We're live. I'm Jay Fidel. This is ThinkTech. More specifically, this is likeable science on a given Tuesday with Ethan Allen, our primary scientist here who tells us about science and makes us like it even if sometimes it's hard. So the title of the show, Ethan, unless you forgot, is exercise protein mimicking as a way to improve our immune system. And that is very relevant in the time of COVID. Why did you study this subject? Well, this was actually, it's a long line of work. People have really been searching for this fountain of youth as it were for centuries and centuries, right? And people have, you know, regularly claim they found the magic elixir that will, you know, help reverse aging and all. And some years ago, some scientists discovered a very interesting thing. If they took a young mouse and hooked its circulatory system up to that of an old mouse, the old mouse really profited from this. Basically, the old mouse showed a lot of signs of getting younger. They did better on a lot of memory tests and sort of old mouse cognition tests, mouse thinking, you know, and they seemed like they were getting sharper. And I think their body ratios changed. They got more muscle, less fat. And then they discovered the same kind of thing. If you just pulled drew blood from a young mouse and put it in an old mouse, you could, if you did it repeatedly, you could get the same kind of effect. But these guys have now taken this sort of one step further and they were, they were, they looked at mice who were exercising versus mice who weren't, even though these are both old mice, but all of mice who were exercising regularly who had access to a running wheel in their cages, basically. And for a couple of months, they could run every day and mice will run on a running wheel day in and day out at night, mostly, but they'll just run and run and run and run for hours. And when they then actually pulled the blood plasma, they got rid of the red blood cells, just stuck the plasma into these old mice who didn't run all the time. What they found was these mice grew new protections in their brain, new neurons at a rate similar to what young mice do. They scored better on, again, on mouse cognition tests, but as they were sharper, they remembered things longer and better. And they showed these very signs of essentially regaining youth, even though they were getting plasma from old animals, but they were old animals who were exercising. It really emphasizes this key role of exercise as an anti-aging phenomenon. Oh, can I, can I buy this at Longs? You already have it in your body, actually. We have, this is an enzyme produced in our livers. It's got a long, complicated name. I think, I think it's, so they just use the abbreviation GLDP1 or something, GLPD1, sorry. And it's known, it basically starts, when you exercise, you produce more of it. One of the interesting things about this enzyme is it doesn't actually get into your brain. There's a, as you may know, you're something called the blood-brain barrier. And a lot of stuff that circulates in your blood won't make it into your brain. But apparently, this enzyme triggers a lot of other things that actually, then some of them do make it into the brain because, as I said, the brain starts reactivating and growing new cells at a faster rate. That growth in new cells really slows down in old age in the brain. So why not just get that, that enzyme instead, the one that's triggered, the one that lives in the brain and use that? Well, they don't know exactly what that is. There's this enzyme, they do know it's produced in the liver, has effects in the liver, it has effects on muscles, it has effects on the brain. So they don't really, they haven't sort of tracked that next step down. But as I say, they've gone from sort of whole blood from a living young mouse now to a single, down to a single protein. And it doesn't matter whether it's from a young mouse or an old mouse actually, it'll do that same kind of thing. It helps rejuvenate your brain at the very least. The study did not, I think, look at the muscles or immune systems. It really looked just at the brain. But yeah, fascinating stuff. Well, yeah, so, but we do have a name for it. It's a long name. And I suppose we can extract this from one mouse to another, as you said. And likewise, we can extract this from my blood and give it to someone else or a young person, give it to me. And then I get presumably I get the benefit. But the mission is to extract it. Now have scientists been extracting? Can they put this stuff in a test tube and then give it to me by, you know, an injection or infusion? It probably could. I mean, probably what's going to happen is that they're going to run some tests on. I suspect they'll just start engineering some bacteria just to make the stuff, you know, just to crank out and relatively pure form because that's going to be a simple way to do it rather than trying to pull out. Are we back to CRISPR again? Yep, exactly. Useful technology, you know. You bet. And once they do that and start testing, it'll be interesting because, as I say, we have this enzyme. It's perfectly natural stuff. It's in our bodies. So there shouldn't be huge hurdles with getting approval to test it out because, you know, it's something we have. And it'll be interesting to see what where this leads. It's a real interesting advance in sort of the science of re-aining youth, you know. Yeah, well, I mean, now I can think of, for example, if I have one blood type and the donor has another blood type and this is, you know, kind of derivative off the blood type, then I may have a headache when I take some from somebody who's not a universal donor or a donor with my blood type. I guess they don't know yet. They haven't tried this. Yeah, this protein should be invariant among blood types. There's been no science I know that says proteins vary with blood types. So once you pull this pure single protein out, the blood type stuff shouldn't matter. Yes, if you were actually taking somebody else's blood to do this, you need to have them either matched or be the universal donor of negative blood. Okay, let's assume we have a system that can pull it out and it's free of the characteristics of the blood from which it came. It's pure. And you give it to me. I guess the first question is, how much can you give me without having an adverse effect? And I'm thinking of, you know, anything really could give you an adverse effect if you took too much of it. Water can give you an adverse effect if you have too much of it. So, no, that's not really been tested. This is a very just a new study. It's just in my so far. They did it for, I think it was a period of eight weeks in mice, which is a long time for mouse. I mean, that's a chunk of it, a lifespan. So it might be something you need to do over a period of months or even years to get to see the benefits in people. I'm not, again, it's not known. I'm sure people are probably putting in applications for the studies for the phase one studies already, you know. Yeah, Ponce de Leon. They're going to have no trouble getting the volunteer for this one, right? I mean, it should be relatively safe. And, you know, there's a whole bunch of people who are getting old who don't want to lose their cognitive abilities, you know. Okay, so far, but you so far, you've talked about cognitive ability. I'm sure I'd like to have a better brain. I'd like my brain to be young and, you know, growing new cells at a rapid rate. You know, I remember years ago, when we would have a drink of gin, for example, in a bar, you remember they used to have bars here. Seems like a long time ago. And the guy would say, you know, this is going to kill X cells in your brain. And they're not going to regenerate, or at least not at the same rate, not the same volume. I still believe that. I think that that glass of gin is at a permanent effect. But in this case, I suppose you can grow new ones as if you were a kid, even a young kid in developmental years. And then you're smarter and you have, maybe you can remember better and think better and all that. But how does this go to the question of youth in general? How does it go, for example, through my muscles and my nerves and all those systems, my organs? Is it just the brain? Or is it more? Yeah, they did not, in this particular first study, look at other impacts. They didn't look, as far as I know, at muscle mass. That's been a traditional way they look at it, because old mice tend to lose muscle and gain fat. That's a lot of people do, too. And so, when you're looking for a marker of rejuvenation, you look to see does that ratio change? They get more muscle and less fat rather than their sedentary mass control group. And I don't know, but this enzyme, as I said, it's a liver enzyme, it circulates widely in the body, and it is thought that it has triggering impacts on other enzyme systems throughout the body, throughout other endocrine system organs, and throughout with muscles, too. So, yes, it may well impact the immune system. It might well impact the muscles. And you might, that almost seems like a, almost a cheat, right, to be able to do that, to get the benefits of exercise, about exercise. Yeah, well, you know, I mean, I'm sure we've all had the experience of doing a long running race, a long swim, what have you, even a long hike, when you were stressing out your muscles and, in fact, your whole body, really. And when you were finished, you felt just great. You felt more alive than you did at the beginning. Your senses were heightened. That's a runner's high, right. You might be tired, but you felt stronger. I remember many times in my own experience for that. So, it's got to be a secondary effect. It can't be just the brain. This particular enzyme has to go other places, too. Right. I mean, exercise basically causes the release of these endogenous opiates that we basically have in our own bodies called endorphins. And when you sort of flood your system with endorphins from a good long bout of exercise, yeah, you feel real good. Not to mention sex. Not really. I mean, endorphins, all that. But can we get to the question of the immune system now? Is there any indication that there's a connection between these enzymes, this mimicking of the mimic protein and the immune system? Again, the study was not looking at all of that. I'm sure people will start looking at that. There are probably experiments going on right now. People are looking at exactly that to see if these old mice start building up better immune system populations of the right kinds of cells. Because again, there's a very classic decline in immune function during age, and it's been pretty well documented in standard laboratory animals like mice. And certain classes of your immune cells get lower and lower frequency, basically, than they are in your use. And so I'm sure people will start looking at that. And there's certainly a reason to think that this enzyme could be doing it. It appears to have a huge number of effects and a huge number of systems. So it's not doing the good itself, but it's apparently triggering other releases of other enzymes. It's probably triggering other enzymes. It's probably triggering other enzymes. And that's where you're getting your real impacts. It's these cascading effects. So yeah, in this day and age, if they found something that would particularly give in coronavirus its impacts on the elderly, that would be a double whammy good, right? There's so many things about the body we don't fully understand. I mean, there was a speaker, he was Western in Canada here a few years ago, spoke at the university. We had him on the show. And he talked about the bacteria in your gut. This is like a new science about how it gets there and how long it stays there and how your bacteria, your mix of bacteria is different from all the other bacteria in the world. And yeah, your microbiome, they call it. The biome, right? The microbiome, right? I believe I am. Because yeah, you have billions of cells in your body that aren't yours. You have probably at least as many cells that aren't yours as you have of your own might be some more cells aren't yours. They're not just your gut, they're in your skin. You can actually, you leave a fingerprint. You're also leaving a little bacteria with that fingerprint that, again, that population of bacteria pretty much uniquely identifies you. It's like a check on the fingerprint as it were. If people actually go to the trouble of amplifying DNA from these bacteria, they can find, yep, that's your particular population of umpteen kinds of bacteria in a certain ratio. Yeah. Wait till the police find out about this. Well, they know about it, but it's a little tricky. There's so little that it's pretty touchy science to do with the tiny amounts. You can imagine there aren't all that many bacteria stuck on a fingerprint. Well, so my point in raising it is only this that, you know, there's a whole system there in the biome that is, we're still learning about it. We're learning what's in the biome, how it interacts with itself, how it interacts with your gut, how it interacts with your general health, how you can tune your general health by tuning your, you know, that there's pills you can take to replace your biome. And when your biome is sick, you know, you're going to be sick and there's all this stuff that I wouldn't say it's medical science. It's biochemical kind of science. It's at the research edge is what it is. Yeah. Yeah. There is evidence now that your biome can influence conditions like depression quite, quite interestingly in that there are some early work that suggests that, yeah, if you take essentially the microbes from somebody who's not depressed and help sort of seed the guts of the depressed person with those, those microbes that can end up alleviating depression, you know. Yeah. Fascinating cutting it and stuff. Although, although this whole thing about the biome is not life and death, it can affect other processes which can be life and death. Who knows what. The reason I mention it is because I think, you know, the immune system is another one of these systems, biochemistry's in our body that we have really not studied until recently. And the immune system is very complex. And in the case of the immune system, it is life and death. Well, yes. And I mean, it ties very closely because this microbiome, these are foreign cells are living in you. And your body does not reject them. Your body is happy to have them there. Your immune system recognizes them somehow as friends rather than foe. And now interestingly, some can play both roles. Some bacteria are perfectly good when they're sort of sitting there quietly in your intestines, for instance. But if they inadvertently get inside you and get in your bloodstream, then they're rather bad for you. So there's, you know, it's a hugely complex subject. And the microbiome, immune system, to nervous system, to hormone system, those are all, we used to look at those very separately, separate silos. But now we realize that we've all sort of merged into one another in various interesting ways. Well, it makes you want to be a PhD researcher instead of an MD researcher, you know, I think, because this is this is really cutting edge stuff. And it's different than MD research. It's biochemical research. But I want to go one step further here. And that is, we are traditionally interested in the immune system because it makes us immune. It makes us immune from diseases we've had. It has those special, what do you call those special things that protect us from having a disease again. It's been all the rage and testing for antibodies and all that. We learned about that in high school biology. But the immune system is much more complex than that. It can save us or it can kill us, too, if it goes out of control. And it's related, I suppose, to kind of inflammation issues. And there are lots of, what do you call it, non FDA medicines, non FDA approved medicines, like in the health food store and the nutrition store, where you can buy anti-inflammatories and take them and it's supposed to control the inflammation process of the immune system. And then we really need to talk about the cytokine storm, because that's part, you know, it's funny that this was being discussed pretty regularly at the beginning of our experience with COVID a few months ago. You haven't heard much about it, but it's still part of all that stuff with the ventilators and you can't breathe and your lungs fall apart, they degenerate while you watch and you die. And part of that is the cytokine storm. Can you talk about the cytokine storm? Yeah, it is like your immune system goes a little bit berserk sometimes. I mean, that happens in other conditions sort of a classic case, it's poison ivy, right? Poison ivy doesn't actually, that the oil from the poison ivy leaves does not actually do anything to you, other than it actually changes the shapes of some of the proteins in your skin. And then those proteins are seen as foreign. And so your body just starts reacting violently, those, it feels like you're being invaded by all these foreign proteins. So it reacts violently. That's why you get all the lumps and welts and pustules of poison ivy, sort of the same kind of thing with the cytokine storm. In the COVID case, it happens at the surface of your lungs. For some reason, your body basically goes into immune overdrive basically and sort of says, my God, I'm being attacked all over. I've got to start pouring these things out. And they change the properties of the little capillaries in your lungs where you're getting your oxygen and either they sort of punch holes in, or they make them leaky, or they clog them up one way or another. Obviously, once your lungs get really fouled up, you're in very big trouble, right? Because you're being three minutes without air and you're dead, right? And it kills you. Yeah, it certainly can. So the cytokine storm is really interesting because we start out with that high school biology notion that your immune system saves you. It makes you immune to disease. It's much more complicated than that. And your immune system can kill you. And so the idea is you want to have your immune system running at the right level. You don't want too much because that'll be very detrimental. And you don't want too little because then it won't function properly. Do you remember many years ago that they had a few bubble boy children who were born essentially without immune systems and they would put them in these sort of sterile environments basically to protect them now? Because yeah, if you don't have a functioning immune system, the world's not a friendly place to be. Yeah, so it's going to protect you from all manner of antigens, viruses, bacteria, all those things that can get you. But if it gets unleashed in the wrong way, and I'm not sure we fully understand what starts the cytokine storm, then it's going to attack your own body. You wind up killing yourself with your immune system. It's something very ironic with that. Right, but I mean that is like the parallel I made with Poison Ivy. You're reacting against your own body there and your immune system is sort of needlessly gone into overdrive because of this little oil, which it really doesn't care about, but the effects of that little oil on your own proteins in your skin turns out to drive your immune system sort of nuts. So the idea is to try to moderate your immune system to keep it alive and well, but not to let it go into overdrive. Do we have a handle on how to do that? Unfortunately, not a great one. There are, you know, obviously, there are ways you know how you can damage your immune system by, for instance, staying up all night or doing shift work where you change your sleep patterns every few weeks. Those things are just devastating to your immune system. It's pretty well recorded now that the people who do that, they get sick a whole lot more basically. Your diet has some effect on your immune system, a good diet to keep your immune system in better balance basically. And as you said, your biome too. Yes, and your microbiome. In part your diet of course is influencing your microbiome and that's influencing your immune system basically. It's a very complex web of relationships there. Well, let's take the sleep thing. Everybody always says if you don't get enough sleep, you know, you'll get sick because your immune system will fail you. We have any idea what that is. I mean, it definitely is a relationship. I think that's been known or at least speculated about for a long time. And it seems to me that while you're sleeping, you're knitting up the ravelled sleeve of care, which could be partly psychological, by the way, and which could involve the brain, by the way. So while you're sleeping, you're regenerating your immune system. I mean, I'm just, I'm doing logic here rather than science. But it seems to me there must be a process that happens while you're getting good REM sleep. Yeah, it is pretty well established. Well, I read one recently said simply missing one night of sleep will decrease your immune system function by something like 17%. I mean, it's something really, really, you don't want to do, right? Particularly in this day, you don't want to push your immune system down like that. Yes, sleep allows your immune system, or that is when your immune system sort of revamps itself, reups, gets ready for the next day basically. Again, that's not at least as far as I know, well understood. But again, I'm not an immunologist at all. So it's a huge and complex field. It could be that you could find an enzyme that would mimic sleep just the way this protein mimics exercise. And then it would help you regenerate your immune system, even if you didn't sleep or do the things you should do to rest your system and let it do a better day. But now here's the final question, though, just looking at the totality of our discussion today. So if you can get this enzyme to mimic the protein you get with exercise, and if you can, you know, refresh your body, well, refresh your mind first, we're not sure about the body, but let's assume that you also refresh the body. Then maybe that has something to do with the immune system too. If it's going to make you more healthy, it seems that maybe would make your immune system more healthy. It would be like sleeping, it would be regenerating your immune system and maybe moderating and tuning it. So it didn't do strange things like cytokine storms. What do you think about that? Is there anything out there that suggests there's a connection? Yeah, again, it hasn't been really looked at, but it's not an unreasonable thing to suggest. Again, regular exercise helps keep your immune system in good shape. And it may be that the release of this particular protein, GLPD1, is part of that process. So it is possible that the injections in this would actually not only make your brain function better, but make your body function better too. And your immune system. Right, well, that's what I'm trying to tell you. So bottom line, you know, we're all interested in staying alive these days. And I must say that after all this time, six months of intense news on all the cable channels, and we still don't really understand what this disease process is, or what the infectious process is. If they say mask one more time, I'm going to scream, it's got to be much more complicated than that. And the infectious process has got to be much more complicated than, you know, than sneezing and coughing and what have you. So the question is, how do you live your life in a lock up or a semi lock up in order to make sure your immune system is working at the optimal level with or without this, this protein mimic process you talked about? Well, the answer seems to be a very simplistic approach. Exercise, take a walk. Yep, exercise, go to bed at the same time every night, get up at the same time each morning, eat a healthy diet and exercise. I mean, in this particular or this particular milieu right now, you want to avoid big crowds of people, you particularly want to avoid big crowds of people inside places, particularly inside small plate places that don't have much air circulation. So you want to stay outside, you know, keep physical distancing enough for people, you know, be sure there's plenty of fresh air around. And yeah, I mean, that's the best thing you can do. It's interesting. I think a lot of people don't really fully appreciate that, that if you maintain decent health and, you know, decent rest and decent eating and decent hours, you're going to be helping your immune system and your immune system will then help you. Yes, absolutely. There's a nice synergy that goes on there. And to break that cycle down can begin to go wacky pretty quickly. And the other thing that comes out of this, I don't know exactly what your lifestyle is, Ethan. Mine is I stay at home. I do this with people like you. I work on think tech and so forth. I don't go out much. I don't go to crowds. I don't go to restaurants. I don't go to events. I pretty much minimize my experiences out on the street. And so I think to myself, well, how long is that going to last? Even assuming we have an economy or maybe we don't, that's what I do. And I don't see the end of it. I don't see this as in chapters. I see a slow roll into a new way of living together in society. And hopefully, if you behave yourself, you'll be there. But one thing is clear, it's not going to be the way it was. So these little rules you and I have been discussing, they're not just temporary. Right. Yeah, I think you're right. Because while we may, and we probably will get this COVID-19 under control at some point in the next several years, who's going to say when the next new virus is going to pop into us? It's going to happen sooner rather than later. And so, yeah, we won't know how contagious that one is, how deadly it is. It's all those questions that have to be addressed again. So we are having more new diseases pop up these days than we used to. Because in part, people are intruding, there's more people, they're intruding more tightly into where animals live. There's more close contact between people and various kinds of animals than there used to be. It's easier now to have people move around and spread diseases in the early stage. So, yeah. Yeah. I think you're entirely right. I think, you know, get used to it on some extent. Yeah. Learn to live with it and thrive in it. Because it's not going away. The really disappointing thing is this. You and I were talking about the Black Death, the plague in the sixth century and the 14th century. And again, to some extent in the 19th century, including here in Hawaii in the form of the bubonic plague. And what is interesting is that as humanity develops, as our society develops, the possibility of epidemics and pandemics increases. And what is extraordinary is that we as a society have not really understood that. We are always reactive to it. We don't really prepare for the next one. We don't have systems in place to deal with the next one. And if there's one thing that comes out of COVID, hopefully, we will remember it. We will prepare for the next one. Because this is part of life on the planet. Yeah. Absolutely. It's been part. And it's been, I mean, ever since Edward Jenner first demonstrated that cowpox basically can protect against smallpox. And you look at the curve of smallpox infections in the years following his discovery is more and more people started doing it. Death rate from the smallpox dropped and dropped and dropped until we eradicated smallpox from the planet. So we can do it. And vaccines are amazing and wonderful things. But yeah, there's a lot more microbes out there than there are people. And the other thing is we've been living, the species, we've been living on this planet in our current form for a couple of hundred thousand years. It's not that much time, but a couple of hundred thousand years, maybe more. And our bodies are a survival of the fittest through all of the pandemics that have existed through that time. All of the diseases we somehow have survived. And part of that survival is the immune system we've been talking about here on this discussion. So inherently in our bodies, there are the lessons we have learned. We as a species have learned to stay alive all these years. So it's interesting how when you think of it that way, we have the answer not in the stars, but in ourselves. Yeah, isn't evolution a wonderful thing? Nice to be alive, Ethan. Ethan Allen, my good buddy in science. Thank you so much, Ethan. Thank you, guys. I'm always happy to talk with you. We'll do it again soon. Take care. All right, go for it then.