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that's a . 7 big business in money, it's not about the public and given them the service that they deserve. it's not about quality train workers. it's about with a welcome to. so if you could visionaries me, sophie shepard not said, i mean human body is wise and knows how to regulate itself. but every mechanism, even though the most perfect one, it needs it wasted button. while today, i talked to david rubinstein, professor of molecular world, we were genetics that cameras universe today and we're talking about the mysterious

phenomena of a tougher. gee it's so great. have you on our program today? so 1230 is like the topic. everyone's talking about it, lots of myths around it. so we figured we'll just ask you straight away, what is all this fuss about from what i understand. so correct me if i'm wrong, a ta for g like process, we're self deprived of nutrients. they sort of get rid of damage structures and develop nuance. is this a correct explanation? i clarify with absolute so it's a process that occurs inside cells and it occurs outside the nucleus. so in the cytoplasm, and it's a process where cells form these double membrane structures which are like sax, which capture portions of high the plasm and then deliver them to water, the incinerator of the cell, the lies for degradation. so that's what we'll tufty is as a process,

the idea that it's stimulated by starvation is something that is conserved from he's to people, but it's not always induced by starvation. the other ways of switching it. all right, so let's clarify what, how do we make the cells go into the out of such a stage. so. busy that number of signals that can make a cell go into that type of process. one is if you deprived of nutrients and it can happen with different types of neutrons. so if you deprive cells of amino acids, they can go into this type of process. if you prod though a glucose, it can go to this process. if you deprive them of energy, it can go into this type of process. it can also go into this type of process. if you switch on some genes that might be involved in cancer for instance. so it is not restricted. the singles are not restricted to those. that all cell stresses caused by by tom nutrient deprivation includes them in like

a very common language. what would you say is a short way to actually start kick, start that process and the human body you from sitting at home and i decide i'll try this because a ta for g supposedly is very good for my organism. it's prevention cures, all search of diseases. so i want to try what should i do? so i don't think that we know enough about that in a humans to do they expect enough to gave me a mouse, nor to do to the mouse. if i stop the mouse for long enough, i couldn't jesus offered you many different tissues and many labs have assist, how long you might need to do it to get it delivered to the brain. for instance, in a mouse, in a human the date also clear. so there's one study i'm aware of where they've looked in different cells in the plant and in only one of the cell types that they studied after 24 hours starvation could they see a change in all tufty now? they said they couldn't see it,

and the other cell types that they analyzed in the blood, i suspect the same as occurring in many other cells in the body as well. so some cells might respond to 20 falls, where many others might not. and so those are unknowns in the field, and i say if you want to really kickstart ta city, they probably you could to, they certain drugs that might do so. but they're probably not drugs that you want to take with how to prescription or you could get with how to get to the drugs part for sure. but the price is professor austin oreos to me who actually got a noble prize for describing the phenomena. he told me recently from what i could understand is that it only can take up to 30 minutes for your cells to go into a tougher g. if, why we stop, there is so suddenly stop their signal. so you can see it move forward, curry, you can see they're all the fishy oak as star within 30 minutes or something.

well, the professor zooming, he's, he's been a pioneer working on the process, but he's really studied east case. so if you study yeast or you sir, study seldom tissue culture. so you, you study them in a very artificial environment. that if you starved them, you can see effect sort of 30 minutes or an hour. that if this is putting that when you stop a cell in tissue culture, you putting the cells virtually nothing when you putting them of water with a little bit of salt. okay? if i did that, your body fall apart, so that your body, of course, when you starve it, it's a much longer adaptation to the starvation. if you star for 30 minutes, you body doesn't know about it at all. crystal for a long time, and you still have all the constituents of the bladder in the theorem and the bodily fluids, which are not like salt water. so i think it's moving from an artificial context in

the laboratory isolated cells and culture to a whole organism. and that's why the 30 minutes is no make sense. i don't suppose is worse asking you if you practice the tougher g just would look like it was about losing weight. so i think, you know, the 2 parallel discussions, the one discussion is whether some degree of caloric restriction is beneficial for people. and the 2nd is whether those benefits are primarily mediated through tougher g. i don't think the answer to either is certainly model organisms like mice. i'm. there are some dates and there are some daily and humans actually that alternate. they fostering for instance, improves various medical parameters of interest. but it's unclear whether those effects in mammals are primarily mediated through sausage. he,

it's just mind boggling to me that you are telling me since the very beginning of this chat that we don't know the exact results on people. and on the other hand, we have this whole movement for a coffee and people are promoting and they're basically books coming out and saying how amazing this is for you. and this is like the answer to practically being immortal. why do you think i want to be walked? i think that there's a fairly good literature and complete work. but this, there's a sizable literature that argues in model organisms that if you can switch on top of gee, in general, it has been official effects. so. so that's the one argue there's also literacy just suggesting a more organisms if you calorie restrict that's beneficial. it's also a letter just saying that if you tell you restrict to mouse for long enough you will use will. tufty. but those old individual strands and the

calls, the links between those strands have often not been tested in a rigorous way. so i would say that we need to learn more and do more experiments to try to understand if that's the case. but you can do that in a mouse, we can do it in a zebra for sure. a word, it's very difficult to switch. awful tough, a whole person's body to do a rigorous experiment. you can't actually to do the rigorous experiment in people and so experience and people are restricted in that way. from what we know so far. let's go through what a tough a g can. what benefits could it have on humans from what we know so far? anderson that we don't have the research. i tried to ask this question to present a professor resuming, and he was very lacey's to say the least, and maybe i can get some answers for you. for instance, i have a colleague who is crazy about alpha gee. and she is actually adamant at telling me

that are her teeth got completely healthy after she started practicing a ta for g? is, is, is something possible, or would you say it's more or psychosomatic? well, or topic, she influences many different systems in the body. so it, it, it's roles are to protect against starvation. it's roles are, i'm to prevents the growth or certain organisms and tissues. so it has certainly and he fixes properties, it can reduce inflammation. that might be relevant to friends teeth and it's protects against certain neuro degenerative diseases by stopping the formation of or the stopping the accumulation of proteins that tend to clamp in the brain and that cause various dimensions. um it's it can affects and the certain into mune diseases by reducing inflammation. so it can be protected with heart disease. so it

has a wide range of benefits if you can induce a to model organism systems. and if you impede it in mice, for instance, then you can create a whole lot of manifestations will make a many, many these disease models worse to understand correctly. primarily it is because it's anti inflammatory. no, that's one of its properties. i think it's possible that the anti inflammatory properties might have much widespread implications across a range of diseases than some of the other will. specific roles that i think there are quite good data in quite since in your a degenerative disease models. that if you switch on or off the g a u m amplified, then you can protect against certain diseases. and then i called lamers perkins data with those types types of those types of diseases i think when yeah. what

about i've heard somewhere also that it could help things like bone fragility, as this a myth node. some of your topics, you machinery and can affect the bone fragility. and my think those were oldest studies and it's not clear today whether they are specific towards healthy g, or just parts of the machinery down. we're going to take a short break right now when we come back. we'll continue talking to professor david robinson here in cambridge, and we're talking about what is a tougher to stay with us. with

join me every 1st been on the alex simon sure. when i was speaking the guess on the world politics sport. business, i'm sure business. i'll see you then. oh, the wrong one i just don't know. i mean you well, yes to shave out. disdain becomes the attitude and engagement equals the trail. when so many find themselves worlds apart, we choose to look for common ground. oh is your media a reflection of reality in the world transformed what will make you feel safer?

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a very dangerous man with b and were bad, was dated. rubinstein here in cambridge talking about the phenomena of a tough g. david, whatever the brain itself, i'm not talking about degenerative diseases like alzheimer's or parkinsonian dementia. but how does it affect our brain if it could be practiced on a human body? so there is a literature which suggests that's a tough achieve might be important in a whole lot in your own will find sure i'm it can remove various toxic proteins as we've discussed. it can also help remodeling. so it can,

i've changed our capacity to remember potentially it's, can this also literature that it's suggest that it might impact various psychiatric diseases, although the literature will that needs more work. so i would say that this, this suggestions which need further work to validate. so i think it might affect a wide range of different cognitive as well as emotional functions. and i'm thinking cancer because you're saying what are the functions as the anti inflammatory infection? so what can i do for cancer? so the cancer literature is complicated and the likely plays different roles. busy at different stages of cancer, so if you have an organism which lack of a tougher g, then it is more prone to the initiation of a primary cancer. ok, what happens and what frequently kills patients?

not the initial primary cancer, it's after spreads to other sites. it's called metastases. and when you got met a static cancer, then it is believed that's a tough and you protect the cancer cells from dying. so then you want to inhibits, we'll talk that she has that sort of a slightly simplistic view of the situation. but it's meant to illustrate that at different stages of the cancer and potentially from one cancer to another different effect. so it plays role. but i think that when you said something about human organism that has less a toss a g or more or off a g. and that's very interesting to me. this is in our talk with professor resuming . he also said something about that it's off, which is governed by genes, guess, and that it's part of our design. if you have other 80 genes that mean

there are, so i have those can machine to turn over the their own protein. so what, like if i have wrong change, i can't trigger a tougher g. very interesting. so there are some very rare cases, very unlucky people who have mutations in coal ta for g teams and they often have early on sits. so they have very little tufty, and they have an early on sit brain disease and you're a degenerative disease. so it is governed by jeans. and with this severe dysfunction, you get those types of diseases. and it is possible that the variance, which have very small effects, which we don't understand in terms of their population impact, does the lack or the opposite of a ta for g in one's body has anything to do with immune system?

yes, i think it does. and particularly in terms of the inflammatory process, but there are other immune functions that are also quite tightly regulated by all tufty. yeah. and at some point some day we were learn, it will, would learn how to trigger a tougher gene, our bodies. and actually, you know, exercise it off a g to better ourselves, but does a tough, a g level in your body, gro was time with exercise like muscles grow. when you exercise in a gym or your brain cells you have or a memory for us in a sense basically. yeah. train. if anybody's really looked, that's quite an interesting idea whether you could sort of in a sense, prime yourself, isn't that right? you respond better to so i don't think anybody's looked at that. um i'm not aware of that. let's put it that way. here's a tip. you should look at why get no more so

you said except for the calorie reduction. there are other ways to trigger. yes, but you can exercise sugar, you guys can trigger in certain circumstances, certain types of exercise in the muscle for instance, like i think the, well i think you to, if you, again, if you make mice to certain types of exercise, it can trigger on top of g, and i suspect some people, if you do certain types of exits, i will trigger a tough a g. but when one reviews the literature, again, it's a little bit mixed. am i having the reasons why it might be mixed? i few healthy away. she was sick the type of. ready exercise, and then many of the studies haven't been done in people they've been done in mice . and so, you know, translating once you've gotten a mouse to what you've got in a person, needs a different type of experiment. it's worth having a lot to look. here's what i understand from what we understand about average. now

it can be an answer to lot of things too, or too many diseases or prevention, at least by the way you think it's more prevention or curing? i think it's often more prevention. i think delaying the onset, you've got a better chance with diseases possible might be able to very difficult secure diseases. it might be some infectious diseases, for instance, which might be amenable to. we'll talk to g as one among a number of agents. they being combination of helping to cure, but many cases predict back to my thought, what i had a notion is that you have the gold line theoretically that were sitting on top of g that hadn't been fully examined or practice and humans that could be an answer to a lot of things, right? you're saying on mice, we know what happens on humans. we don't because it's very hard to practice or experiment on humans. so there's this gap between mice and humans and what are we

going to do with it? i mean, are there any plans or any methods to actually do experiments or humans or we're just going to sit there forever and talk about? no, no, no, no, no, no, i'm look, it's look fairly new fields. i think that's, you know, when i started working almost at the turn of the century, we knew very little about the genes in mammalian science. so there's in 20 years, we've got a fairly good idea about the genes. um, you know, we and others are starting to try to look at ways that we be able to assess, even if it's in directly what is going on a little tougher. g, him different tissues insurance already people are looking in the blood. and i think we will have to start looking in other tissues. so all correlates and other tissues that will be informative in order to answer those very important questions . so you, you're just saying it's question a time until we actually tie where this question of money. but money, and i mean, you know, so it's

a question of time and money that's i think people are going to be looking at more and more in future because, because exactly what you said, that's, it's a process that has potential for impacting many different diseases. and i'm potentially, i'm healthier aging so, so i think we do need to understand these processes in humans. how would a human actually know that he has trigger at the top of g? i do early way of knowing would know. i think we would need to biopsy something, so in the blood you can just take blood. you might, if you wanted to see what was going a little muscle you'd have to your muscle biopsy, probably. well, you'd have to find a marker which gave you an indication less we'll talk with you what's happening in the muscle. so something less invasive, but you'd have to measure it in some type of formal sense. do you know a lot of big farmers are actually starting to look for a drug or create

a drug that would artificially trigger a ta for g in the human body. i don't know if you've heard about that. i know. so is it a, or i can't figure out a good thing or do you think it should have been naturally? i think it's probably a good thing we interested in that area. and the reason is that i think you'll be able to probably, it depends which tissue once and so if you want to st induced or ta for gene, the brain probably have to solve a very long time. the brain takes a long time to reflect how love it. we don't know in the mice, probably to starve for close to 24 hours. okay, but that's my sure you'd have to do a much longer human. and so there might be ways that you can activate or tough achieve specific tissues much more effectively with the drug and potentially with much better targeting. so you might be able to induce all tougher genes, certain places without affecting other cells as well. so i think m r is what people

are trying to do, and i think it's because of the magnitude of the effect as well as the potential to restrict defect to certain tissues. so if you look generally at our cells, processes in our cells as what defines our health. yes. basically, do you think we can ever hope to harness those processes in actually may be steerer them where we would like them to? i think that more and more i'm medicine is relying on what to call rational drug discovery. and that is based on the understanding what's going on in cells. and so if you understand better how cells work, then we can identify pinch points that we can attack in order to switch process is pulled down with much better control. and so you have to, you're right, we need to understand the fundamentals of cell biology. so are you like in a team of those people who are actually saying yes,

medicine and biology is entering this new breakthrough. this is like an apostle lurch and everything is going to be completely incredible. and nothing's going to be same again when we're talking about relatively like trans card, trans blends and drugs from aids and a low cloning. genetic engineering, are you as enthusiastic as money or do you think it is? it's, i mean, it's the, the way the tools for understanding biology have evolved in the last 25 years. he's just remarkable. i mean, treaty remark one, you know, when i was a students, nobody could dream of the prospects of taking human cells and removing every single gene one at a time to see how it affected a particular process. and know those types of approaches are becoming almost routine and so that gives us the prospect of really understanding the way. so human cells in the human body works much better than ever before. and we really

have technology and i think it's, it's that was would have been considered a dream 25 years ago. but i thank you very much for this interview. thanks for clearing up. lots of, let's about a tough a gee, and hope to get that money soon. good, but your research so we can start practicing. thank you very much. ah, b u is in the process of finalizing what is being called the strategic compass for security and defense. this is shorthand for what may become an e u army. this is not a new idea, and there is no guarantee that will ever come about. is europe capable of defending

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