aah holcomb to sophie co visionaries, me sophie shepard, knots and when human body is wise and knows how to regulate itself, but i get every mechanism even though the most perfect one. it needs a recent button. well, today i talked to david rubinstein, professor of molecular rural, newer 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 to name so tar for g is like they topic everyone's talking about it. lots of myths around it. so we

figured we'll just ask you straight away. what is all that fuss about 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, but it's a process that occurs inside cells and it occurs outside the nucleus. so the cytoplasm and it's a process where cells form these double membrane structures which are like sax, which capture, pushes us high to plasm and then deliver them to water, the incinerator of the cell, the license for degradation. so that total ta for g is 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 on. all right, so let's clarify what, how do we make cells go into the artifact stage?

so. busy their 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 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 go into 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 stress is caused by some nutrient deprivation. but it did include them in like a very common language. what would you say is a sure way to actually start kick start that process in acumen body you've, i'm sitting at home and i say, i will try this because a tougher g supposedly is very good for my organism. it's prevention cures,

all search of diseases. so i will try, what should i do? so i don't think that we know enough about that in humans to do the experts in that you gave me a mouse, an or to do to the mouse. if i stop the mouthful long enough, i can induce alt offered you many different tissues and many labs have assist how long you might need to do it to get it to the liver versus the brain. for instance, in a mouse, in a human and 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 or tufty. now they so they couldn't see it in the other cell types that they're analyzed in the blood. i suspect the same as occurring in many other cells in the body as well. so some cells might respond or to 24 hours, but many others might not. and so those unknowns in the field,

and i say if you want to really kickstart tufty that problem, 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 you couldn't get with how to get to the drugs part for sure. but the price is professor or she norris to me who actually got a noble prize for describing the phenomena. he told me recently from what i could understand, 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 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 study seldom tissue

culture. so you study, they may know very artificial environments. and if you stop them, you can see effects after 15 minutes or an hour. but he's just putting that when you stop a cell in tissue culture, you putting the cells virtually nothing. can you put them of water with a little bit of salt? okay. if i did that, your body, you for the, for the part, so that your body, of course, when you start it, it's a much longer adaptation to the start ation. if you store 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 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 can. so that's why the 30 minutes is can you make sense? i don't suppose is worth asking you if you factors that offer 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 topic. i don't think the answer to either is no, it 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, 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 that wants to be walked? i think that there's a fairly good literature and complete work. but there's a, there's a sizable literature that argues in model organisms that if you can switch hummel tough a, 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 carry restrict, that's beneficial. it's also a letter. just saying that if you tell you restrict a mouthful long enough, you will end useful 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 gina 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, understand that we don't have the research. i tried to ask this question to present a professor is in the and he was very, they safe 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 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 are, i'm to prevents the growth or certain organisms and tissue so it has certainly and seen 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 did stopping the accumulation of proteins that tend to clamp in the brain. and that cause various dimensions. um it's, it can affects and 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's 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 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 court since in euro degenerative disease models. that if you switch on top of a, you amplified, then you can protect against diseases. and then i call timers perkins data with those types. types of those types of diseases. i think when you what about i've heard somewhere else so that it could help things like bone fragility as this emit nodes. 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 hoford's or just parts of the machinery they were 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 tough stay with us. oh, the postal service delivers a $155000000000.00 pieces of mail every year, approximately 40 percent of the world's mail right now. the us postal service is in the fight of its life essays that is really bad financial shape. now facing default

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sure don't seem to vicious mr. fisher from one of the, from the tech up here with some dinner, was the discussion to fill that out and walk you through a group on yet the future brookwood in the so there's a lot on that when you're beside bixler. i me at that with him and i bet she can usually sit almost by you. so what i wanted to look up in did is it looked at us once and she lives by right. you have the key moments it, shes leeway and she should be

aware bad was dated. rubinstein here in cambridge talking about the phenomena of a ta for 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 a remove, there is toxic proceeds as we've discussed. it can also help remodeling. so it can have changed our capacity to remember, potentially. and it's can, ah, this also literature that it's suggest that it might impact various psychiatric diseases. although the literature will that these will work. so i, 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. what i'm thinking cancer, because you're saying what are the functions as to 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 um has a lack of will ta for g, then it is more prone to the initiation of a primary cancer. ok, but what happens and what frequently kills patients? not the initial primary cancer. it's after spreads to other sites. it's called a metastases and when you got met a static cancer, then it is believed that or tougher g protects the cancer cells from dying. so then you want to inhibit towards half a t s. so that's 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, a different effect. so it plays role, but i think they complicate welly, you said something about human organism that has less a tougher g or out of more a ta for gen. that's very interesting to me because in our talk with professor resuming, he also said something about that at average is going by genes. yes. and that at its part or design, if you have a, a t g genes that mean they're so have those kind of machine to the terminal, but they are proteins. what like if i have wrong genes, i can't trigger a tough a g. very interesting. so there are some very rare cases,

very unlucky people who have you taishan in coal tough g teams and they often have early on sets. so they have very little tougher g. i'm have a early on sit brain disease and you're a degenerative disease. so it is governed by genes and when this severe dysfunction, you get those types of diseases. 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 photography 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, we mean functions that are also quite tightly regulated biotechnology. yeah. and at some point, some dave, we were learn it, we would learn how to trigger a tough a gene, our bodies. and actually, you know,

exercise it offered you to better ourselves, 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 a memory for this. 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 any money is looked at that 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 can exercise sugar can trigger in certain circumstances. certain types of exercise in the muscle for ins, 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's 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 what you've got in 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 of our coverage now . it can be an answer to lot of things, pure too many diseases or prevention, at least by the way. 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. it might be some infectious diseases, for instance,

which might be amenable to will tough a g as one among a number of agents maybe in combination. i'm 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 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 do experiments or humans or we're just gonna 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 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 be able to assess, even if it's in directly what is going on a little tougher g in different tissues insurance. so really, 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 at time. until we actually call tie where the so christian of money, but so money there, i mean, you know, so it's a question of time and money threats. and i think people are going to be looking at more and more in future because because exactly what you said that it's a process that has potential for impacting many different diseases and, and, and potentially 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 a ta for j? i do early way of you would know. i think one would need to biopsy something. so in the blood you can just take blood and you might, if you wanted to see what was going a little muscle, you'd have to do a muscle biopsy probably. or you'd have to find a marker which i gave you an indication less than what's offered. you was happy me in the masses, 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 ta for g in human. but i don't know if you've heard about that. i know. so is it a go? 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 am, 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 here 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 starve for close to 24 hours. okay, but that's my sure you'd have to do much longer the 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 targets. and 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. basic, which 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 processes. i pulled down with much better control. and so you have 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, madison in 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 cart, 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 says, 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 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 upset was would have been considered a tree 25 years ago. but a thank you very much for this interview. thanks for clearing up. lots of next about a ta for g and hope to get that money soon. good, but your research so we can start practicing. thank you very much.

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