July 12, 2013
Podcast from: https://bengreenfieldfitness.com/podcast/anti-aging-podcasts/natural-anti-aging-strategies/
[00:00] Introduction
[02:10] About Dr. Aubrey De Grey
[04:08] How Dr. De Grey Started in this Field
[08:34] Why Aging May Not Actually be Inevitable
[13:02] 7 Strategies for Increasing Longevity
[20:32] Enzymes That Keep Your Body From Building Up Junk
[45:56] Cutting-Edge Strategies to Keep Us Feeling Good When We Live Long
[1:03:28] End of Podcast
Ben: Hey, it’s Ben Greenfield and I want to welcome you to this special episode on anti-aging. In just a moment, you’ll have the pleasure of being able to listen to one of the world’s experts on anti-aging, give his take on the whole issue. Now, I’m a brass tacks, practical application kind of guy, and frankly, I was a little bit surprised at some of the answers that I got from this guy Aubrey De Grey. So, after the interview finishes, I’m actually going to delve into some of the things that I want to contribute to the discussion because, frankly, Dr. De Grey is a busy guy. I had limited amount of time to be able to interview him and not only that, but towards the end of this interview, I was personally getting a little bit of an annoying echo back into my own headphones that was incredibly distracting every time I spoke.
So, don’t push stop on the podcast or erase it when you hear the interview with Dr. De Grey wrapping up because I have some really practical takeaways that I want to give to you at the end. And then, of course, if you visit the show notes for this episode at BenGreenfieldFitness.com or you click the little “e” if you’re listening right there one the app, you’ll get access to all of the links to everything that you hear Dr. De Grey and I talk about and also that I talk about after Dr. De Grey and I finish.
So, let’s jump right in.
Ben: Hey folks, it’s Ben Greenfield here and I gotta tell you, I’m pretty excited about today’s podcast guest because he is an expert in a field that sometimes tends to fly under the radar, but that every single one of us, despite what we think we may be pursuing when it comes to getting a better body, or thinking more clearly or enhancing fertility or losing fat. We’re all kind of chasing the one thing that this guy is an expert in and that is anti-aging: helping our bodies to actually last longer and do what they’re supposed to be doing while we’re alive. And, I’ve been able to hunt down the top antiaging expert on the face of the planet. His name is Aubrey De Grey and he’s… he’s relatively famous in this area. He’s technically a bio-medical gerontologist based out of a combination of the UK and then also California. And, he has founded the SENS Research Foundation and he’ll be explaining what SENS stands for today for us; it’s actually a pretty cool concept. He has a BA and a PhD from the University of Cambridge and his original field was in Computer Science, but he’s now involved in rejuvenation research. He’s a fellow of the Gerontological Society of America and the American Aging Association and he sits on the editorial and scientific advisory boards of a ton of different journals and organizations. He’s a huge wealth of knowledge when it comes to anti-aging. So, pretty honored to have you on the show, Aubrey, and welcome to the Ben Greenfield Fitness podcast!
Dr. De Grey: Well, thank you, Ben, for having me.
Ben: So, I gotta ask you that… this seems like kind of an interesting field to be an expert in. I’m curious about how you got involved in this. What kind of drew you to this whole field?
Dr. De Grey: Well, it’s really a combination of two things. First of all, something that, with a lifelong passion and secondly a discovery that I made when I was around 30. So, the lifelong passion was simply to make a difference in the world. I always had a lot of options available to me. I’ve always done well academically ever since I was a kid, and somehow I decided at an early stage in my life that what I wanted to do was to dedicate my time and my efforts throughout my life to things that would improve the quality of life of humanity. So, fundamentally, I was always a humanitarian sort of person and that’s actually why I got into computer science. I was attracted in helping the research to develop artificial intelligence because it seemed to me that it was a great shame and a great tragedy that so many others were really have to spend their time doing menial stuff: going down mines, serving hamburgers, whatever it may be just to keep society going when we’re actually much more equipped and better and could have a much better time if we could spend all of our effort and that time doing social stuff, enriching each other lives.
So, it seemed to me that it was high time that we developed ways to automate all of the tedious stuff. And of course, automation has come a long way in terms of manufacturing and agriculture over the past century or so, but there’s a long way to go in terms of automating other menial things. And, the more we do that, the better people’s quality of life will be. So, that was why I went into artificial intelligence research.
And then, when I was about 30, I made a big discovery and it was a big, shocking discovery. I had, by that time, for a few years had been married to a biologist who I met when I was 26 and she was a lot older than me. She was already a full professor in San Diego, actually. And, we met when she was on sabbatical in England. And through her, not only did I learn a lot of biology, just informally over the dinner table, but also, I eventually realized that she wasn’t interested in aging. And then eventually I realized that hardly any biologists were interested in aging but weren’t really studying it and I thought this was extraordinary because aging obviously kills far more people than anything else in the world put together and it causes an enormous amount of suffering as well. And therefore, it seemed to me that it was clearly biology’s most important problem and yet it wasn’t being treated that way.
So, eventually I decided well, this is an even more urgent and serious humanitarian challenge than the challenge of delivering artificial intelligence. So, I happened to be in a very fortunate situation where I could switch fields pretty much without any risks. So, that’s what I did.
Ben: Interesting, interesting. And so, from there, you’ve gone on to… I mean, I know that you wrote a book. What’s the name of your book? I don’t have it in front of me. Is it “Ending Aging?”
Dr. De Grey: That’s right. I’ve written two books actually. The first one with a much more technical thing that was essentially my PhD thesis about 15 years ago now. But, the one you’re talking about is the general audience one which was published about 5 years ago, “Ending Aging”. Yes.
Ben: Gotcha. And, for folks who may have seen you without realizing it, you also have an enormous beard.
Dr. De Grey: [Chuckles]
Ben: Is there a story behind that or is that just… your style?
Dr. De Grey: I guess. The story is my wife likes it. My wife is a beard fanatic and the time we met, back in 1990, I had never had a beard and I wasn’t really very keen on growing one. But, she campaigned for it and after about five years, I gave in and gave it a go and it came out like this. It grew from nothing to this length in only two years. So, I was just as surprised as anybody.
Ben: Well… well, it’s a good look. I’ll be sure to put a picture of you in the show notes to this podcast so folks can go over and see what Aubrey looks like- very impressive beard. So, Aubrey, let’s jump into the nitty-gritty of this. I’ve seen in writing before you saying something to the effect that you think that aging is somewhat inevitable. Do you really think that aging is inevitable?
Dr. De Grey: Well, that depends what you mean. What we can certainly say is that aging is an intrinsic side effect of being alive in the first place- an intrinsic side effect of the normal operation of the human body. Just like any other machine, a simple man-made machine like a car for example, the normal operation of the human body generates side effects, generates damage, molecular and cellular changes to the structure and composition of the body and those changes accumulate throughout life. Now, in that sense, therefore, yes, aging is absolutely inevitable and indeed there is a minimum, an absolute minimum rate, at which this damage will be generated as a side effect of simple things that we have to do that are non-negotiable, like breathing and eating. These things are going to happen.
What’s not inevitable is that this damage should remain unrepaired. Medicine is all about restoring health to the body and there’s absolutely no reason why we should not have medicine that restores youth to the body that repairs this ongoing accumulating molecular and cellular damage and thereby keeps it below the level that causes disease and disability. Because, of course, there is such a level, right. The reason why someone age 40 or 50 like me is still functioning just as well when I was 25 is because the threshold below which the body is set up to tolerate a certain amount of damage. It’s only when the damage accumulates beyond that threshold that things start to go wrong.
Ben: So, how long do you think that people could actually live if they were to unlock this process of defying a lot of the natural things that happen to us as we live and breathe and move?
Dr. De Grey: So, if you think about what I just said about comparing the human body to a simple manmade machine, you can say that there’s no answer to that question. In just the same way that we can keep vintage cars on the road working just as well as when they were built for as long as we like just by periodically doing this preventative maintenance removing damage before the doors fall off, right. Similarly, for the human body, we can just periodically do this preventative maintenance and there’s no reason why we shouldn’t be able to do it indefinitely.
You know we don’t have… yeah, we have hundred year old cars. They weren’t built to last 100 years, they were only built to last only 10 or 15 years. We don’t have any 200 year old cars for the reason is not because we don’t know how, it’s because cars weren’t invented 200 years ago.
Ben: You used to be involved in something called the Methuselah Project. Correct?
Dr. De Grey: That’s correct. The Methuselah Foundation.
Ben: And Methuselah is a character from the bible who lived… he lived more than 900 years, right.
Dr. De Grey: So the Bible says.
Ben: Yeah. So, do you think that’s something that’s potentially possible using some of the strategies that we’ll eventually talk about a little bit later on in this interview?
Dr. De Grey: Well, absolutely. I mean, we chose that name for that foundation back in 2002 certainly because it evokes understanding of the possibility of healthy longevity. You know, Methuselah in the Bible is not supposed to have spent 800 years of his life in a frail and diseased state. The idea of that is he was youthful at that time and that’s what this is all about, remember. This is not about longevity. This is all about health. This is all about keeping people in a truly youthful state, by physically and mentally, for as long as they live. And, any longevity benefits that we may see, however dramatic those benefits may be, they’re purely a side effect of maintaining health and therefore maintaining one’s risk of death in the coming years, as we say, at the same very low level that it was when one was a young adult.
Ben: Right and that’s what’s kind of mind blowing is that when we think of old people, for example, we think of wheelchairs and nursing homes and diapers and all sorts of really unpleasant scenarios and what you’re proposing is that the human body can actually operate well into a much higher agent than what we’ve expected- a much higher capacity than what we’ve grown accustomed to.
Dr. De Grey: That’s right.
Ben: So, let’s jump into some of the strategies here because I’m all about the nitty-gritty and the application and you, personally, had outlined seven different strategies for ending aging based on the seven causes of aging that you’ve identified. So, let’s first talk about the causes of aging; you’ve identified seven causes of aging. What are those causes?
Dr. De Grey: Okay, so, well first of all. Yes. First of all, “causes” is not really quite the right word to use.
Ben: Okay.
Dr. De Grey: I think the best word to use is mechanisms of aging. So, what we’re talking about here is the types of damage that accumulate in the body throughout life as side effects of the body’s normal operation and which eventually overwhelm the body and contribute to the emergence and progression of ill health and disease and disability. And, the next thing I need to clarify is that these are types of damage. So, if we actually enumerate all the different mechanisms of aging, then it’s a large number. And, the big insight that I had back in 2000 that led to the work that SENS Research Foundation does, was to realize that these very large numbers, the different examples of damage, can be classified into this manageable number of categories. Just seven categories. This classification is useful because, as we will talk about shortly I’m sure, we can actually describe for each of those seven categories a generic way of repairing them or obviating them- making them harmless. And thereby, we can talk about a manageable strategy for actually comprehensively rejuvenating people and keeping their damage level low.
Okay, so, to enumerate what those seven types of damage are, there are three cellular ones and four molecular ones. If we start at the cellular ones, the first one is simple loss of cells– gradual reduction in the number of cells in a given tissue and this happens simply when cells die and they are not automatically replaced by the division of other cells. So, that’s simple enough.
Then, the other two are both of the form of having too many cells. And the reason there are two is because there are two generic ways of having too many cells of a particular type. One, is if the cells are dividing when they’re not supposed to and that of course is exactly what cancer is. And the other is if they’re not [15:28]______, that’s something that a lot of people overlook but it’s actually very important especially in the aging of the immune system. Sometimes cells absolutely need to die in order for other cells to have the space to divide later one and the immune system especially needs that. That goes wrong late in life.
Alright, so those are the three cellular ones. Now the molecular ones. They fall into two sub categories. There are two types of molecular damage that happen inside cells and two that happen in the spaces outside the cells between cells. So, the ones inside cells, first of all there are mutations in the mitochondria. The mitochondria is this really special critical part of the cell that does what you might call “the chemistry of breathing.” It combines oxygen chemically with nutrients in order to extract energy from those nutrients- energy that’s used for all the other things that the cell has to do. And, mitochondria are unique in a cell in that they have their own DNA. Most parts of the cell don’t have their own DNA, their genes and proteins are all in the nucleoli in the nucleus and our normal chromosomes. And most of the proteins that make up the mitochondria are also encoded in the nucleus, but 13 of them are encoded in special DNA in the mitochondria and that DNA accumulates mutations and that means that things go wrong. We have plenty of circumstantial evidence that this has a very widespread general effect, ubiquitous effect, in driving the process of aging. So, we need to fix that.
The next one that’s inside cells is a much more straightforward one. It’s simply the accumulation of molecular garbage – just byproducts of normal metabolic processes, byproducts that for whatever reason the cell does not have the machinery either to break down or to excrete. So, that just means it accumulates and it’s easy to see how that’s a problem because if you don’t take the garbage out of your house for a month, then the house doesn’t work so well. It’s exactly the same inside the cell. This turns out to be the reason why we get cardiovascular disease because of oxidized cholesterol accumulation in cells in the artery wall. It’s why we get macular degeneration, the number one cause of blindness in the elderly. And it’s because of a different type of molecule that accumulates in the retina. It’s also seen in all the various types of neurodegeneration: Alzheimer’s, Parkinson’s, and so on. So, it’s a really, really important component of aging.
Okay, so now we’ve got two left and those are the types of molecular damage that happen outside the cell. The first of those, is again, molecular garbage. Same deal, except that this time it’s outside the cell and I’ll be talking later about why I’ve added a separate category. So, examples of that are amyloid which accumulates in the brain and Alzheimer’s disease also in the pancreas during type-II diabetes, also in the heart throughout life actually, and this seems to be a major cause of death and heart failure in the very elderly. Various other examples of what we call extracellular garbage, and again, it’s the same deal. We have to actually repair this damage in order to make sure that it doesn’t contribute to ill health.
The final one is, again, outside the cell, but in this case, it’s not garbage. In this case, it’s chemical changes to a lattice of proteins. Proteins that have the important function in giving our bodies and our organs their shape and the biophysical, the mechanical, behavior that they have. This lattice is called the extracellular matrix and it’s made of proteins that are laid down early in life and are essentially never recycled. So, those proteins need to be recycled and when they are things are repaired, but when they’re not recycled, they accumulate molecular damage over a particular type that’s really dangerous namely crosslinking chemical bonds between adjacent proteins. That reduces the elasticity of the extracellular matrix and that makes it stiffer and that turns out to be really important for various types of aging in particular the artery wall which is hardly recycled at all. This accumulation of additional randomly located molecular bonds causes high blood pressure. It causes hypertension and I’m sure you know that hypertension has effects that have relevance to different aspects of aging including kidney failure, for example.
So, those are the seven types of damage.
Ben: Okay, got it. Now, for people who are out there perhaps listening to this while they’re running or they’re bicycling, we all know you’re IQ drops by 10 to 15 points whenever you’re moving around or listening to a podcast and Aubrey just totally dropped a knowledge bomb on us, so to speak, with all of these different mechanisms of aging. So, Aubrey, if you don’t mind, do you mind if I poke into this a little bit with you on each of the things you just mentioned just to clarify a few things for folks and maybe talk about some of the solutions that people can utilize to stop some of these aging mechanisms that you just explained to us.
Dr. De Grey: You’re most welcome; go ahead.
Ben: Okay. So, one of the things you talked about was basically how aging leads to this accumulation of junk outside the cell, this extracellular junk.
Dr. De Grey: Yes.
Ben: Now, when that junk accumulates, what is it? How does that actually do damage? I mean, how can people visualize what extracellular junk is actually doing inside their bodies?
Dr. De Grey: Well, okay, let’s talk about intracellular junk first because it’s a little bit easier to describe.
Ben: Okay.
Dr. De Grey: So, it’s actually the single easiest thing for a non-biologist to visualize because it’s so similar to what happens in everyday life. So, I mentioned a moment ago the analogy with not taking the garbage out of your house, a certain amount of garbage in the house is fine because you have garbage bins that you put it into and it doesn’t even smell much if you don’t actually interact with it, if it doesn’t do any harm so long as there is a manageable amount of it. And if you take it out every week, then everything carries on working however long you like. That’s exactly the way to think about molecular garbage inside the cell. If the garbage bin in the cell, it’s called the lysosome, and molecular stuff that the body can’t break down, that the cell can’t break down, generally ends up in the lysosome. In fact, it pretty much always ends up in the lysosome. The lysosome is a really powerful garbage disposal machinery – it’s like an incinerator, really. It’s much more acidic than the rest of the cell, it’s got dozens and dozens of enzymes that break down molecular structures that can’t be broken down anywhere else in the cell, but even the lysosome isn’t completely omnipotent. There are things that the lysosome can’t break down and so that’s why things accumulate in there. Now, the lysosome can accommodate a lot of garbage, but not an infinite amount. As the garbage accumulates, the lysosome gets bigger, but of course the lysosome can’t get bigger indefinitely because the cell has other stuff that needs to happen outside the lysosome. So, eventually the cell gets impaired in terms of all of its functions just because of the mass action of the excess, because there’s too much of this garbage around. If we can get rid of that garbage, then the cell recovers, just as if you take the regular garbage out of your house.
Ben: Now, the lysosome is using enzymes to break down this garbage right?
Dr. De Grey: It’s using enzymes to break down as much garbage as it can, but there’s some residual garbage that none of those enzymes work on. That’s why it accumulates.
Ben: So, one strategy then, would you say, to somehow give your body additional enzymes or support your body with a type of enzymes that the lysosomes would be using to break down this junk?
Dr. De Grey: That’s exactly right. So, in fact, this is exactly the proposal I put forward back in 1999 originally – well, that’s when I had the idea. We’ve been working on it since then, but in the laboratories since about 2005/2006. The idea is that other species have different enzymes than what we have. In particular, bacteria are extraordinarily versatile, there are enzymes there that have a whole manner of different capabilities that we don’t have. So, the idea then is to find bacteria which have the capability of breaking down things that accumulate in our body because we don’t have the right enzymes. Once we can find the bacteria that do that, we then look for the genes and enzymes that they use to do that. And that turns out to not be very difficult for both of the major targets that we have gone after so far, which are the major molecules causing atherosclerosis, cardiovascular disease, and the major one causing macular degeneration, it has turned out to be pretty easy to identify bacteria which can break down the offending molecule and also find how they’re doing it, the enzymes and the genes that are involved.
So, the next step after that is exactly as you just said, to introduce these enzymes into our own cells. Of course we start out, not by injecting anything into the body, but rather by doing experiments in cell cultures in the laboratory and that’s what we’re doing at the moment. Last year we had a great success on the cardiovascular disease side of this project where we were able to introduce an enzyme to human cells, an enzyme that was found in bacteria. We had to modify it in various ways so that it would work in the new environment of the human cell, in particular so that the enzyme would go to the lysosome and still work, but we got that to happen. So, not it’s possible to give human cells high amounts of this very toxic molecule called 7-ketocholesterol that’s the main driver of cardiovascular disease. And, the cell survived while they don’t survive if they don’t have this enzyme.
Ben: So, is this an enzyme that you can get from just eating certain types of foods or is this some kind of a patented enzyme that you’re developing in a lab or something like that?
Dr. De Grey: The patent situation is irrelevant to this. What matters is that you can’t get any enzyme of this sort into the right place by eating it. You have to actually have the cells that need it to make the enzyme internally using genes that we introduce by gene therapy for example. Alternatively, there’s one other way of going about it which is to inject the enzyme into the bloodstream and then, if you modify the enzyme in an appropriate way, it can, in principal, be taken up by the cells that need it. But, if you just eat it, then the enzyme gets destroyed in the intestines, in the stomach, before it can be transported into the bloodstream and then into the cells that need it.
Ben: Got it. So, for people listening in, is there anything that they can do right now to enhance their ability to clean up intracellular junk or keep it from spilling out and becoming extracellular junk?
Dr. De Grey: Honestly, no, to be honest. The problem at the moment is that the therapies of this sort require modification, either genetic modification or stem cells so that the cells which need it, which are white blood cells, have the ability to create the right enzyme. Or, alternatively, as I said, we can inject the enzyme into the circulation, but that is also not perfected yet. However, it’s close. For the past few decades, there has been a type of therapy called enzyme replacement therapy which is designed to help people who are genetically deficient in one or the other of the enzymes that most people normally have in their lysosomes. I remember a few minutes ago I said that lysosomes are chockfull of enzymes that break stuff down, of course those enzymes are encoded by genes. So, just as for other congenital diseases, there are some people out there who don’t have one or another of these enzymes because they’ve got mutations in the gene. And, that means that they accumulate molecular garbage in their lysosomes much more quickly than you and I do. And these diseases are, therefore, fatal really early and usually in childhood. But they can be treated by this method- by making a large amount of enzymes in the laboratory and then injecting it into the circulation every week, maybe. And it really works if you modify the enzyme appropriately so that a sufficient proportion of it is taken up by the cells that need it, then you’ve got people who would have normally died at the age of five and they’ve been living perfectly healthy adult lives ever since. And the only that’s wrong with their lives is that they have to get injections every week.
So, this really works. It was easier though than the job that we have for something like cardiovascular disease because in that case, all that was necessary was to synthesize large amounts of the same enzyme that normal humans already have. In this case, it’s a bit more challenging because we’re taking an enzyme that no human normally has, we’re taking it from a different species like a bacterium, and we have to make modifications that are foreign to the human body. So, we have other challenged like immune rejection and so on that we have to find ways around. Now, we know broadly speaking how to do that, but it does mean that it’s not ready for primetime quite yet.
Ben: Okay. So, if people want to keep their finger on the pulse of this development of this enzyme or this injectable therapy, what would be the best way for them to do it?
Dr. De Grey: Well, certainly going to our website SENS.org. It‘s always the best way to keep in touch with everything. We have regular updates on all of our projects, as well as, of course, comprehensive reports that we publish every year giving thorough information about all the work that we do. We’re actually very close, probably a couple of weeks away from publishing our latest annual research report which will talk in detail about all of the projects we’re doing. About a month of two ago, we published our annual report of the more generic type which has a lot of information about financials and so on, but which also had a big section on the research. There’s not a lot of detail on the research report itself, but it’s a very good place to start. But yeah, you can go through our new news updates on our blog, you can look at all of this stuff very easily, and of course, anyone who has specific questions that they can’t find answers to on the website, they’re always very welcome to send us a question through the website through the query interface.
Ben: Now, there are some other things that you talked about, one was crosslinking and the idea that proteins can form these crosslinks which sugars and that can contribute to tissues aging. Now, is this the same thing as these advanced glycation end products or AGEs that we hear about?
Dr. De Grey: Yes, it is. To be more precise, it’s a subset of AGE. So, the reaction that we’re talking about here is actually not just one reaction. It’s a complicated and very [30:32] ______ sequence of reactions and it starts with the circulating sugar molecules, they’re on our bloodstream, attaching to amino acids in proteins. This can happen inside the cell as well, but I don’t think that there are any real consequences inside the cell because the proteins which are modified in this way inside the cell have a rather short half-life. They are recycled rapidly. It’s proteins that have a very long half-life because of very little recycling that are the problem, and they’re mainly ones outside of the cell.
Okay, so a sugar molecule attaches to an amino acid that’s part of a protein that’s part of the extracellular matrix. After that, there’s only a matter of things that can happen and many of the advanced glycation end products that you hear about, I think, are probably harmless because they don’t cause cufflinks. They only just sit there and rearrange and they become stable modifications of individual amino acids, but they won’t have any effect on the elasticity of the extracellular matrix. It’s just that occasional sequences of reactions that then having attached to one amino acid then also attach to another amino acid on a neighboring protein – those are the problematic ones. So, those are also advanced glycation end products, but it’s just a subset of them.
Ben: Okay. Got it. Now is this simply a matter of being careful with combining sugars with proteins or avoiding eating heated baked products and those types of things we hear about or are there other things that you’ve found in your research work better or most efficacious?
Dr. De Grey: Well, key thing to remember here is that we can’t actually stop this from happening. We need sugar. Sugar is an absolutely essential nutrient. Of course you can have too much sugar, but there’s a minimum amount of sugar you absolutely require because you’ve got to have it to burn to make energy to do all the things that the body has to do to keep going. So, these reactions are going to happen at some rate below which you cannot go. Now, the question of whether you can exacerbate this problem by eating food that already has advanced glycation end product in it, that’s actually still a very open question. It’s quite controversial. My personal view is that actually the problems caused by food which has a lot of advanced glycation end product in it, it’s not caused by those products because those products either do not get absorbed into the bloodstream at all, they just stay in the gut and get excreted, or in the cases where they do get into the bloodstream and into cells, they don’t do any harm because they don’t get incorporated into new proteins and therefore they can’t cause damage.
Now, you can think of ways whether it might cause damage even if they’re not incorporated into proteins, but they’re pretty artificial theories. And, there’s certainly no evidence for that at this point. However, food that have a lot of advance glycation end product in it probably also has a lot of other molecules in it that you don’t really want to be eating. So, there may be other reasons not to consume such things.
Ben: So, what do you think at this point would be the number one way to try and limit the amount of crosslinking that happens in your cells?
Dr. De Grey: I’m afraid really that there’s not a lot we can do. You know, this is really a generic and all of the things we work on at SENS Research Foundation, the reason we work on them is because nobody else is really working on them.
Ben: Right.
Dr. De Grey: The reason nobody else is really working on them is because we’re still quite a long way from actually delivering therapy. It’s really quite early-stage research. But, if nobody tries, it’s going to stay early-stage research and we’re never going to be able to fix these things. You know, it’s quite a disappointing and demoralizing fact, but it is a fact, that at the moment aging is inevitable. There’s nothing that you can do today that will let you live until 150 or even until 100 in good health, or even until 80 in youthful health.
Ben: Gotcha.
Dr. De Grey: Okay. The only way to really increase your chances of living youthfully for a lot longer than you would with today’s medicine and today’s technology is to improve on that medicine. In other words, to hasten the development of medicines that do not yet exist, to hasten the pace of medical research that organizations like SENS Research Foundation are doing.
Ben: Got it. Well, I’ve got a few other questions for you, but I definitely do not want to let you off the hook in today’s interview, I want to make sure that we give people some hope, something they can do, some practical takeaway they can use at least at some point. Something.
Dr. De Grey: Let me do that for a moment.
Ben: Okay.
Dr. De Grey: I do sympathize and obviously people are asking me these things. If I had any better answers than the answers that the MDs that you’ve probably have on the show all the time will give, then I would be telling you. But, the fact is, if there were easy answers, then we would have been using them already. There’s not even a dietary answer.
If you think about it, the seven billion people on the planet, every single conceivable diet that you can imagine is being tried/has been tried and yet we do not see people living until 150 because they’ve got the right diet or the right lifestyle or anything like that. It simply isn’t possible yet. We need the best of medicine. But, that doesn’t mean there’s no hope, what it means is that we need to go about this in a different way. You need to go about it not just by dedicating your time to living healthily, or whatever, and just hoping for the best. But rather, doing things like what you’re doing right now: promoting and exposing the research that’s being done to actually hasten the development for therapies that really do work against aging, real anti-aging medicine. Not everybody heard our podcast, not everybody has influence over a large number of the public, but everyone has influence over somebody. If you’re wealthy, obviously, you can support the research directly financially. If you’re a scientist, you can get into the right areas of science so that you can actually participate in the research yourself. If you’re not wealthy, you must certainly know somebody who’s wealthier than you are and they probably know somebody who’s wealthier than they are. So, you can pass this up the food chain and get things done. If your parents or your kids are not interested in this, you can get them interested. If your elected representatives are not interested, you can get them interested. After all, the only reason why we don’t get public support for this sort of work is because elected representatives want to get reelected and they don’t see it in the electoral interest, they don’t see this as an electoral class and that can change if more people start to talk about this and start to write to their senators or to their congressman or whatever. Everyone can do something, but the key thing is to have a good sense of proportion about what’s going to be most effective. And at this point, for sure and certain, if there were concerted public efforts to actually promote and advocate for this work, it could go far faster. We could take 10 years off the time it’s going to take to develop this therapy and that’s one hell of a lot of people whose lives would be saved.
Ben: Interesting. So, in other words, rather than popping a bunch of pills and supplements, send this podcast interview to someone you know who could make a difference.
Dr. De Grey: You got it.
Ben: So, you talked about junk, you talked about crosslinking, there was one other thing that you talked about that I wanted to hear. You talked about mitochondrial mutations and cancer causing mutation. When it comes to these mutations, what exactly is going on and is there anything we can do about that?
Dr. De Grey: So, these two are the two hardest components out of the seven for sure. These are really cases where the description of the SENS approach as damage repair is perhaps not 100% accurate. It’s more like the obviation of damage, making the damage harmless so that it does not contribute to ill health and old age.
So, let’s take mitochondrial mutations first. Here, the difficulty that I mentioned is that we have DNA inside mitochondria. That DNA accumulates damage, accumulates mutations and the result is that the mitochondria don’t work so well, in fact, they don’t work at all. And, cells end up eventually suffocating. Exactly how that contributes to age related health is actually still somewhat controversial but there’s masses of over good circumstantial evidence that says that it contributes very broadly to aging in general. Okay, so, what do we do about it? Well of course the damage repair approach would say let’s fix those mutations, let’s replace the mutated mitochondrial DNA with non-mutated mitochondrial DNA. But, people have been looking for a long time, including myself, for practical ways to do that. And, at this point, it’s still very likely that this will be beyond us- that we’ll simply not be able to replace that DNA.
So, the approach that SENS Foundation is taking, which is an idea that’s been around way before me back in the 1980s it was first explored, is to make the mitochondrial mutations harmless by making the mitochondrial DNA itself essentially superfluous. The idea here is that we exploit the fact that only 13 of the proteins in mitochondria are encoded in the mitochondrial DNA, all the others which makes more than 1,000, are encoded in nucleo DNA already in a normal chromosome. So we could in principal do gene therapy to incorporate copies of the 13 mitochondria genes into a nuclear genome into the normal chromosomes modified in such a way that the proteins that they encode are imported back into the mitochondria and just like all those thousand other proteins already are, and then assemble them approximately into the membranes so that they do what they’re supposed to do. Looking something in which there has already been initial success in laboratories, in other species especially, but also in human cells and we are exploiting some new discoveries that have been made over the past few years to take that further. So, we think this is very realistic now. But, then you can see it’s not really damage repairing quite the same strict sense most of the things we talk about are because we’re leaving the damage alone, we’re just eliminating the mechanism in which the damage causes problems by essentially putting those same proteins back in even though the genes that normally encode the proteins may not be working.
Ben: Interesting.
Dr. De Grey: So, now let’s go into nuclear mutations. So, people may have noticed if they were listening carefully, but I didn’t actually mention nuclear mutations as a category of damage. In other words, mutations in our normal chromosomes. I did however mention cancer via the accumulation of cells which just divide when they’re not supposed to. And, the reason why I do it that way is because I strongly believe, and there’s good arguments for this, that mutations which cause cancer are the only mutations in the nuclear genome that we need to worry about. Essentially the logic is, if just one cell in the whole body gets into a really bad state so that it would divide, and divide, and divide, they can kill it whereas any mutations in our nuclear genome which could cause changes in the function or loss of function of cells but which cannot cause them to divide uncontrollably, that mutation in just one cell does no harm at all because any organ that you may choose, it’s made of a lot of cells, trillions of cells, and therefore a lot of cells need to have the same mutation and the same problem in order for the actual body to notice. This is why I think evolution has been driven by the risk of cancer to make the maintenance and repair of DNA unnecessarily thorough, unnecessarily good, from the point of view of any other damage that may occur. So, that’s why we only talk about cancer. Okay, so then, what do we do about cancer? Well, obviously it’s an age related problem. You get more cancer if you’re older. It’s a really hard problem. In fact, I’m convinced that cancer is by far the most difficult aspect of aging to actually address. And, for that reason, we are giving cancer the respect it deserves. Our strategy, the SENS Research Foundation’s strategy for combatting cancer, is very elaborate, but we believe that it is far more powerful, far more inescapable, shall we say, far more comprehensive than anything anybody else is working on.
The fact that it’s a lab rat, however, is a big problem and I really hope that it’s not necessary. I really hope that all the work we’re doing on cancer becomes irrelevant because other people come up with therapy that works just as well, that really work properly against cancer and which are easier to implement than our strategy is. But, I don’t want to bet on it. I think we would feel pretty stupid if we just tried to fix everything else and let other people get on with trying to fix cancer in their own way and we succeed in fixing everything else and nobody succeeds in fixing cancer and then we all die of cancer before the age of 100 anyway. It would be a bit of a shame really. So, I don’t want to be in that position. So, we’re working on this very elaborate method. The elaborate method involves, first of all, eliminating the ability of cells to extend the ends of their chromosomes – the telomerase that I’m sure many biologists have heard of. There’s an enzyme called telomerase that does this normally and cancer cells usually turn on telomerase. They make a lot of it so as to extend their telomeres despite the fact that the cells are dividing a lot.
There’s another method called alt which we’re working on. It’s a method by which some cancers, about 10 or 15% of cancers, increase the length of their telomeres even though they don’t have any telomerase. The problem, however, is in order to do this thoroughly, in order to make this really work, you have to do it indiscriminately. We have to actually inhibit the telomere elongation function of all cells, not just cells that are already cancerous. This is a way of making sure that cells can’t just mutate to resist the therapy. And, that means that this therapy is going to have side effects. It’s going to mean that our skin and our blood and the lining of our gut get into serious trouble after 10 or 20 years because their stem cells can’t keep dividing because they haven’t got long enough telomeres. And the approach that we are looking at to address that side effect is simply stem cell therapy to replenish the stem cell poles of those few tissues stem cells divide rapidly so as to make sure that those tissues are still maintained indefinitely even though the underlying stem cells are no long immortal.
Ben: Like injectable stem cell therapy?
Dr. De Grey: That’s exactly right.
Ben: Got it. Well, you know we’re running a little bit short on time, but what I want to ask you just to end for folks to give them an example of how they might be able to live in a good way to help them out a bit with the anti-aging processes. How does Aubrey De Grey do things? Do you have certain foods, certain supplements, or types of exercises that you do? What’s the day in the life for you where you’re utilizing some of the things that you know might be helpful?
Dr. De Grey: Well, there’s a couple of things that I want to say before I answer that question directly.
Ben: Okay.
Dr. De Grey: First thing is, I am interested in hastening the development of this therapy whether or not I myself benefit from my own work. I’m in this for humanitarian purposes. Even if I were to succeed by my own work in hastening the development of the defeat of aging by 10 years, that would still only make a few percent of difference to my probability of making the cut, maybe I’m just too old already in respect to what I do or alternatively I’m young enough already if I were working on something completely different. Certainly if I’m in that little gray area in the middle that I actually benefit myself, but so what? The fact is every day that I bring forward the defeat of aging is 100,000 lives saved and that’s what gets me out of bed in the morning. It’s not the personal benefits, it’s the humanitarian benefit.
Second thing I want to say is that every single person is different. So, I am probably not living the sort of life in terms of lifestyle and diet or the amount of sleep that one gets that would be optimal, in a sense I’m probably shortening my own life a little bit by the way I live. But, it’s worth it because I’m hastening the defeat of aging by a larger amount. Also, everyone is different in the sense of their own metabolic composition. It’s well known that I drink quite a lot of beer and it doesn’t do me any harm, I still have a BMI under 20 and I weigh exactly the same as I did when I was 17 even though I am now 50. I cannot really word in terms of all the numbers you might want in terms of one’s blood work. A lot of people who drink the amount of beer that I drink would not be that way, that’s just because I’m genetically lucky. Some people take a lot of supplements, I don’t take any supplements and that doesn’t mean taking supplements is wrong, it means that you need to pay attention to your body and make sure that what your body needs, depending on your genetic and epigenetic individually, is provided. There’s no generalization that you can make about that. Any of the books that you may read that tell you to take this supplement or have this lifestyle, those are just lowest common denominators. They may be appropriate for a large proportion of people, but ultimately, your own best doctor is yourself- listening to your body and determining what works, what makes you feel good. That will be what’s actually good.
Ben: Interesting. So, I have a bunch of links that I want to put in the show notes for folks, but do you think that the best resource from people to go to, aside from maybe checking out your “Ending Aging” book, would be the SENS.org website?
Dr. De Grey: That’s absolutely the place to go, yes. SENS.org is obviously designed for general audience. A lot of the stuff there is quite technical for those people who do want to dive into the biological data, but most of it is non-technical precisely because it’s designed to be a way to introduce people to the science. And also, of course, not just to the science, but also to the social context, the reason why this is the world’s most important problem and why the various reservations that people have and concerns that people have about the problems that might be created are byproducts of solving aging, in fact, misplaced and why we don’t need to worry about that at all.
You know, there’s all manner of different things that are [49:52] ______. My book absolutely is the place to go, but it’s quite technical. I mean, it’s not technical in the sense of requiring actual formal biological training, there’s no jargon in there that you need to already know before you start the book, but at the same time, it doesn’t cut any corners. It’s really detailed. So, if you’re not a biologist, expect to want to take your time reading the book and rereading paragraphs and so on. It’s a pretty thorough account. Furthermore, even though it was published more than five years ago now, it’s still pretty up-to-date, not because there’s been no progress, there’s been massive progress, but rather because the progress that has happened has been very much of the nature that we predicted. Things have actually been moving along exactly as we had hoped.
Ben: Got it. Okay, well I will put all this stuff over at BenGreenfieldFitness.com along of course with the wonderful picture of Dr. Aubrey De Grey’s fantastic beard which I know you all want to see. Dr. Aubrey De Grey, thank you so much for coming on the show today and sharing this information with us.
Dr. De Grey: Well, it’s my pleasure. Thank you again for having me.
Ben: Alright folks, this is Ben Greenfield and Aubrey De Grey signing out from BenGreenfieldFitness.com.
Okay, wait, don’t go. It’s me, Ben, again like I promised. You could probably hear that annoying little echo that I was getting as feedback. I apologize. I was not able to cut that out post production.
So, there’s two things that I want to talk to you about after that interview with Dr. De Grey. He talked a lot about these advanced therapies and research that he’s personally doing and I definitely put a great deal of credence into what he says and I think that we’re just now getting into the number of cutting edge therapies that are available to us when it comes to anti-aging and living as long as the human body really is capable of living. Let’s face it, there’s a big difference between the centenarians you see featured in the newspapers who are living to be 110 versus what Dr. De Grey is going after which is hundreds and hundreds of years old. But, I do want to give you some takeaways that you might be able to implement in your life right away that Dr. De Grey and I were unable to explore fully.
So, the first takeaway comes from an articles that appeared in the New York Times last year. It’s called The Island Where People Forget to Die and the article is actually about this island called Ikaria which is close to Greece, I don’t even know if I’m pronouncing that properly, it might be Ikaria. Either way, it’s an island of about 99 square miles and has about 10,000 people that live on it. And per capita, it has the highest level of centenarians and long-living health individuals on it than any other place on the face of the planet. And in this article someone goes over there to look at the demographics and what these people are doing. So, I want to just read to you a few anecdotes that I think are really, really helpful in terms of giving you insight into what’s working for the people who are living long and healthy lives.
So, let’s start here and now I’m going to be reading the article word for word. “Seeking to learn more about the island’s reputation for long-lived residents, I called on Dr. Leriadis, one of Ikaria’s few physicians. On an outdoor patio at his weekend house, he set a table with Kalamata olives, hummus, heavy Ikarian bread and wine. ‘People stay up late here,’ Leriadis said. ‘We wake up late and we always take naps. I don’t even open my office until 11 a.m. because no one comes before then.’ He took a sip of his wine. ‘Have you noticed that no one wears a watch here? No clock is working correctly. When you invite someone to lunch, they might come at 10 a.m. or 6 p.m. We simply don’t care about the clock here.’ Pointing across the Aegean toward the neighboring island of Samos, he said: ‘Just 15 kilometers over there is a completely different world. There they are much more developed. There are high-rises and resorts and homes worth a million euros. In Samos, they care about money. Here, we don’t. For the many religious and cultural holidays, people pool their money and buy food and wine. If there is money left over, they give it to the poor. It’s not a ‘me’ place. It’s an ‘us’ place.”
Moving on to later on in the article: “Leriadis also talked about local “mountain tea,” made from dried herbs endemic to the island, which is enjoyed as an end-of-the-day cocktail. He mentioned wild marjoram, sage, a type of mint tea, rosemary and a drink made from boiling dandelion leaves and adding a little lemon. “People here think they’re drinking a comforting beverage, but they all double as medicine,” Leriadis said. Honey, too, is treated as a panacea. “They have types of honey here you won’t see any place else in the world,” he said. “They use it for everything from treating wounds to curing hangovers, or for treating influence. Old people here will start their day with a spoonful of honey. They take it like medicine.”
And, going through the rest of this article, there are some interesting anecdotes on their diet which is typically a “breakfast of goat’s milk, wine, sage tea or coffee, honey and bread”. By the way, when I say bread, this is a much, much different bread than the type of commercialized unsoaked, unsprouted cheap fare that we tend to see at most grocery stores. Anyways through, breakfast: goat’s milk, wine, sage tea or coffee, and bread. “Lunch was almost always beans like lentils or garbanzos, potatoes, greens like fennel, dandelion or a spinach-like green called horta, and whatever seasonal vegetables their garden produced; dinner was more bread and goat’s milk. At Christmas and Easter, they would slaughter the family pig and enjoy small portions of larded pork for the next several months.
They talk a lot in this article about homemade wine, about laughter, about community and then later on, they get into the diet a little bit more and note that the Ikarian’s diet, like that of the other’s in the Mediterranean, is rich in olive oil and vegetables, low in dairy except goat’s milk and meat products, also low on meat products, and also include moderate amounts of alcohol. It emphasized homegrown potatoes, beans like garbanzo, black eyed peas, and lentils, wild greens, and locally produced goat milk and local honey. They eat very little refined sugar and all of their breads are traditionally made with stone ground wheat.
Now, a little later on in the article there’s a story about the researcher visiting this 90-year-old bee keeper and for dinner she walks out into the fields and returns from the fields with handfuls of weed-like greens and combines them with pumpkin and bakes them into savory pies and also makes a dish with black eyed peas, tomatoes, fennel tops, and garlic finished with olive oils. So, a kind of stew. There’s also quite a bit of talk about antioxidant rich compounds like dark coffee and dark teas and dark wines.
So, I’ll link to this article in the show notes, but what we can take away from it is that a sense of community, a low stress lifestyle, and then a real focus on eating very nutrient-rich, locally grown foods tends to be one of the defining characteristics of an island like this. So, I think that’s one thing we can take away from this study. And, just to give you some statistics, about 83.7% of the men are active and 70% of the women are active and those are people over 80. They have two to three-and-a-half glasses of red wine daily, 10 ounces of coffee daily, almost all of them nap daily. So, I hope you’re beginning to see some patterns emerge here when it comes to longevity and enjoying life and staying healthy and vital into life.
Now, I know that many folks who listen to this podcast, and perhaps yourself are also interested in supplementation and some of the more cutting-edge therapies that go above and beyond what, perhaps, the people on these Greek islands are doing. Well, there are some interventions that I also wanted to mention to you. One known intervention that may be able to delay human aging, for example, is caloric restriction. That doesn’t mean you go out and go out of your way to intermittent fast and beat up your body with a CrossFit session after not eating for 16-hours, but it does mean that you don’t stuff your face 24/7, that you teach your body how to back off so you get some of that natural cell turnover.
Another area to focus on would be growth hormone and hormone support, I would say some of the more important things that you could be doing from that standpoint would be a good intake of vitamin D along with sunlight exposure. I’m also a big fan of some of these natural growth hormone precursors, particularly Colostrum. That’s one that I use in my diet.
Antioxidants are a key. One theory of aging is the free radical theory of aging meaning that when oxygen is using to make energy in your cells, it releases these reactive compounds called free radicals or reactive oxygen species. And, there are a lot of antioxidants out there like vitamin A, vitamin C, vitamin E, coenzyme 10, and sure you get a lot of these from dark fruits and dark vegetables, but if you’re a typical podcast listener to this podcast, you might be exceeding your body’s ability to quench free radicals with the amount of exercise that you’re doing over and above what you’re getting from simple dietary intake. So, getting a good full spectrum antioxidant in is also something that could be quite important when it comes to antiaging.
Now, we’ve also talked a little bit about stem cell therapy and how there are oral stem cell precursors out there that might be a more convenient alternative for you than going in for injectable stem cell therapy and most of those have a base of a marine compounds: algae, spirulina, marine phytoplankton, things of that nature.
So, takeaway message for you here is to definitely keep an eye on Dr. De Grey’s research and what he’s doing. And I’ll put a link to his website in the show notes. If you’re really thinking big picture here, like, going after the 500 or 1,000 year type of scenario. If you want to kind of start small, destress. Take naps. Get a good sense of community and then eat as many local, real food sources as you can: wine, tea, coffee, honey, even milk and bread if they’re in the right form, and yes, even legumes. Al those are fine. I would say the Weston A. Price Foundation and the cookbook “Nourishing Traditions” would be good sources for you when it comes to those types of things. And then, if you want to go after therapies, supplements, things of that nature, I would definitely use a good spectrum antioxidant. I personally do a shot a day of one called Life Shot, it’s a wild plant extract that my personal naturopath physician designed. I would also look into using something like Colostrum compound if you’re not a vegan or vegetarian, that one is derived from animals, but it can be quite potent as a growth hormone precursor. I would look into moderate amounts of calorie restriction. Perhaps you might just even have a fasted day once a month where all you take in is a little bit of greens and some tea and some caffeine and perhaps a glass of wine at the end of the day and you just have a day where you don’t eat anything.
And then finally, look into these supplements that contain marine phytoplankton, algae, spirulina, things of that nature. There’s some good evidence that these may really step up your body’s own ability to upregulate its own stem cell production, cellular repair, and recovery processes.
So, I am definitely not as smart and not as immersed in research as Dr. Aubrey De Grey is, but I also simply couldn’t leave you hanging at the end of the podcast with absolutely nothing to go out of rather than keeping your eye on research. So, I hope that’s helpful for you. I’ll put a link in the show notes to The Island Where People Forget to Die article. I’ll put a link to Aubrey’s website. I’ll throw a link to some supplements in there: that Life Shots one that I take and I’ll hunt down a link to the marine phytoplankton and some good sources for that. And, hopefully you find all of that helpful. Well, of course if you have questions, comments, feedback leave them in the show notes. I’d be happy to start a discussion about this right there in the show notes or even over at Facebook.com/BGFitness.
Alright, this is Ben Greenfield wishing you a long and healthy life. Enjoy the rest of your day. Keep on smiling and I’ll talk to you later.
Dr. Aubrey De Grey (pictured above) is a British researcher on anti-aging.
He claims he has drawn a roadmap to defeat biological aging, and provocatively proposes that the first human beings who will live to 1,000 years old have already been born.
In today's podcast, I interview Dr. De Grey, and we discuss his seven “reasons” for aging and what you can do about it. You'll learn:
-Why aging may not actually be inevitable…
-7 strategies for increasing longevity…
-Which enzymes keep your body from building up junk…
-Cutting-edge strategies to keep you actually feeling good when you live long…
-And much more!
If you want to read more, De Grey expounds upon the following 7 principles and Delivery Systems he is developing:
1. Extracellular Junk
2. Death-Resistant Cells
3. Extracellular Crosslinks
4. Intracellular Aggregates
5. Mitochondrial Mutations
6. Nuclear Mutations
7. Cell Loss and Atrophy
Resources mentioned in this episode include:
–The Island Where People Forget To Die article
–Pacific Elite Fitness Anti-Aging Pack