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various they both are good to hear more of those stories. you can visit our website or dot com. we'll be back in an hour with the latest headline states use. now for sophia and cut a can to so if you could visionaries me, sophie shepherd not said, i mean human body is wise and knows how to regulate itself. but i ever mechanism, even though the most perfect one, it needs a recent button. well, today i talked to david rubinstein, professor of molecular rural, new or genetics at cambridge university and were talking about the mysterious phenomena of a ta for g. it's so great to have you on our program today. so it

is like the top caravans talking about it, lots of met, surround it. so the figure, it will just ask you straight away, what is all that fuss about? am from what i understand. so correct me for iraq. a ta for g, like process where cells deprived of nutrients, they sort of get rid of damage structures and develop nuance. is this a correct explanation? i clarify with f l, 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 push over side of plasm and then deliver them to water, the incinerator of the cell, the lies a zone for degradation. so that's a little tougher. g as a, as a process. um, the idea that it's stimulated by starvation is something that is conserved from his to people. but it's not always induced by starvation,

the other ways of switching it on. all right, so let's clarify what, how do i make the cells go into the artifact stage. so. busy their number of signals that can make a cell going to 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 to paddle glucose, it can go into this process. if you deprive them of energy, it can go into this type pro process. but it can also going to this type of process . if you switch on some genes that might be involved in cancer for instance, if so, it is not restricted. the signals are not restricted to those that all cell stresses caused by some nutrient deprivation. but it did k goods. them in like a very common language. what would you say is a sure, a way to actually start kick start that process in acumen body you've,

i'm sitting at home and any say, i'll try this because a tougher g supposedly is very good for my organism. it's prevention cures, all sorts 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 the ex pumped enough to gave me a mouse and all 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 to the live of us is 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 look 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 or tufty now they so they couldn't see it's in the other cell types that the 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 for many others might not. and so those are unknowns in the field, and i say if you want to really kickstart or ta city, they're 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 couldn't get to get to the drugs part for sure. but the price is professor austin, or as 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 ta for g. if, why we stop there is so suddenly start their signal start. so you can see it move forward. curry, you can see there on the face yolk as star within 30 minutes or something. well, the professor zoom. he's been a pioneer working on the process,

but he's really studied east case. so if you study yeast or you so study seldom tissue culture. so 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 will you store the cell in tissue culture? you putting the cells virtually nothing. when you putting them of water with a little bit of salt. okay. if, if i did that, your body would fall apart. so that your body, of course, when you starve it, it's a batch longer adaptation to the starvation. if you star for 30 minutes, your body doesn't know about it at all. crystal for a long time, and you still have all the constituents of the blood 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 can. so that's why the 30 minutes is no make sense. i don't suppose is worth asking you if you practice the top of gee, just 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 on the 2nd is whether those benefits are primarily mediated through topic. i don't think the answer to either is no, said the model organisms like mice. i'm there are some dates and there are some daily and humans actually that alternate. the fostering for instance, improves various medical parameters of interest. but it's unclear whether those effects in mammals are primarily mediated through we'll talk to you, 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, 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. yeah. why do you think so? want to be what 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 or tough a, gee, in general, it has been official or things so. so that's the one all there's also literacy just suggesting and one organisms if you calorie restrict that's beneficial and it's also literally 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. busy 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 his question to pursue it . professor is in the, and he was very lacey's to say the least. maybe i can get some answers for you. for instance, i had a colleague who is crazy about alpha gee. and she is actually adamant at telling me that 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 as psycho semantic? 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. ready are i'm to prevents the growth or certain organisms and tissues so it has certainly and seen fixes properties. it can reduce inflammation that might be relevant to fred's teeth. and it's protects against certain neuro degenerative diseases by stopping the formation of all the stopping the accumulation of proteins that tend to clamp in the brain that cause various dimensions. um it's, it can affects and the certain into mune diseases. and by reducing inflammation. so it, a kemp will 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 the many, many of these disease models worse to understand correctly. primarily it is because it's anti inflammatory. no, that's one of its properties. i think a bit possible that the anti inflammatory properties might have much widespread implications across a range of diseases than some of the other will. specific roles. i think there are quite good data in quite since in your a degenerative disease models. that if you switch on top of a u. m amplified, then you can protect skin diseases and i called timers perkins data with those types or types of those types of diseases. i think when yeah, what about i've heard somewhere else so that it could help things like bone fragility, as is a myth. knows some of your top would you,

machinery i'm can affect the bone fragility. am i think those were oldest studies and it's not clear today whether they are specific tool toffee, g, or just parts of the machinery there. we're going to take a short break right now when we come back. we'll continue talking to professor david rubinstein, hearing cam bridge and we're talking about what is a tough to stay with us. ah, now a

to see out because the advocate and engagement equals the trail. when so many find themselves world support, we choose to look for common ground. o d u is in the process of finalizing what is being called the strategic compass for security and defense. this is a 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 itself in this competitive world? ah surely don't seem an official mister fisher, someone at that the from the tech hockey i was

with some dinner washed them with a new beside that. so i me at the what the membership usually said, almost failed. so what i'm going to look up in today's to, to test on submission. i saw might yes, the key moments it, she's leeway as she shared it really is no thing. they can't ride on police report it in december 2020 a group of anti finishes. so out a film crew access for 3 months. so if people are organization, if an idea that is

a must be opposed to check out the game while they may come with their faces. but they can say what they believe in. we believe in helping our community. we believe that fascism is one of the major threats to the united states has gotten reuben, this is a chance to see who and t for really are in order for me to extract my 1st amendment right and say that my life matter, i have to be on to the teeth with the police regents was the government, we can't trust anyone except or so to protect ourselves in we 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 ta for g might be important in a whole lot in your own functions i'm it can remove various toxic proteins as we've discussed. it can also help remodeling. so it can have changed our capacity to remember potentially it can this also literature that it suggest that it might impact various psychiatric diseases, although the literature will that needs more work. so i would say that this the suggestions which need further work to validate. so i think it might affect a wide range of different cognitive as well as emotional functions when i'm thinking cancer,

because you're saying what are the functions as the anti inflammatory faction? so what can i do for cancer? so the cancer literature is complicated and the likely plays different roles at different stages of cancer. so if you have an organism which has a lack of a tougher g, then it is more prone to the initiation of a primary cancer. okay, what happens and what frequently kills patients, not the initial primary cancer. it's often spreads to other sites. it's called metastases. and when you got met the static cancer, then it's the believe 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 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 difference effect. so it plays role, but i think the complicated, when you said something about human organism that has less a toss of g or more or off a g. and that's very interesting to me because in our talk with professor resume the he also said something about that a top which is governed by genes gifts and that it's part of our design. if you have other 80 g genes, that means there are. so i have those can machine to turn over the their own proteins. so what like if i have wrong genes at cart trigger tougher g. very interesting. so there are some very rare cases, very unlucky. people who have you take sions in call 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, a neuro degenerative disease. so it is governed by genes. and with this severe dysfunction, you get those types of diseases and it is possible that they are em 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 j 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 the other immune functions that are also quite tightly regulated by all tufty. yeah. and at some point, some day we were learning, we would learn how to trigger a tougher gene, our bodies, and actually, you know, exercise it off a g to better ourselves, does a tougher 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 a memory for it in a sense, basically, i'm not sure 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 which you can exercise sugar. you guys can trigger in certain circumstances, certain types of exercise in the muscle for ins like i think the, well i think you do it again. if you make mice to certain types of exercise, it can trigger on top of g and i suspect to people. if you do certain types of exits, i will trigger all 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? so if you healthy away, she was sick. the type of exercise. and then many of the studies haven't been done in people they've been done in mice. and so, you know, translating what 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. few are too many diseases or prevention, at least by the what do you think it's more prevention or curing? i think it's often will. prevention. i think delaying the onset. you've got a better chance with diseases possible might be able to very difficult, secure diseases that might be some infectious diseases, for instance, which might be amenable to will talk to g as one among a number of agents maybe in combination. i'm helping to cure back to 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 practiced in humans. but it 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 the experiments are humans are, which is gonna sit there forever and talk about no, no, no, no, no, no, i'm look, it's look fairly new field. i think that's, you know, when i started working almost at the turn of the century, we knew very little about the genes and 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're able to assess,

even if it's in directly what is going on a little tougher g in different tissues inhuman. so really, people are looking in the blad, i'm, and i think we'll 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. if you're just saying it's question a type until we actually tie where this question of money but money. i mean, you know, so it's a question of time and money fits 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 a g? i do early way if you would know. i think we would need to biopsy some things in

the blood. you can just take blood. you might, if you wanted to see what was going on the 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 to 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 isn't it? i can't figure out is 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 need to stop for close to 24 hours. okay, but that's my sure you'd have to do much longer in a 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 effect to certain tissues. so if you look generally ourselves processes in our cells as what defines our health. yes. basically, do you think we can ever hope to harness those processes and actually maybe steer them where we would like them to?

i think that more and more i'm medicine is relying on what we call rational drug discovery. and that is based on the understanding what's going on in cells. and so if we understand better how cells work, then we can identify pinch points that we can attack in order to switch process is a pull down with much better control. and so you said 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 polco 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 for 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

says, remarkable. i mean, treaty remarkable. and you know, when i was a student, 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 none of those types of approaches are becoming almost routine. and so that gives us the prospect of really understanding the way. so humans self and the human body works much better than ever before. and we really have technology and i think it's ups 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 gee and hope to get that money soon. good for your research so we can start

practicing. thank you very much. ah look forward to talking to you all that technology should work for people. a robot must obey the orders given by human beings except where such order is a conflict with the 1st law show your identification. we should be very careful about on personal intelligence. and the point obviously is to trace truck rather than fear i would like to take on various jobs with artificial intelligence, real summoning with a robot less protective own existence with

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