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[Damien Blenkinsopp]: Aubrey, thank you very much for coming on the show.

[Aubrey de Grey]: My pleasure, thank you for having me.

[Damien Blenkinsopp]: So, aging is a disease. Obviously this isn’t what everyone thinks today, so why would you describe aging as a disease?

[Aubrey de Grey]: Well, it is actually because that is a controversial use of terminology I don’t tend to do that. I tend to try to sidestep the ambiguity of the terminology, first of all, and cut to the chase. So let’s say whether or not we choose to call aging a disease, what we can certainly say is that it is a medical problem. It is bad for you. It makes your body and your head work less well, and eventually it kills you. And that is what I call a medical problem.

[Damien Blenkinsopp]: Okay, fine. When you are looking at it from this perspective, are there things in previous interviews where I have seen. When we are young we can die and we can get injured from certain things. And when we age, when we are older in our 40s and 50s, we tend to get other health conditions which you could say are linked to aging. Are there certain conditions where you could say that if we didn’t age, we wouldn’t have to put up with these health or functionality restrictions?

[Aubrey de Grey]: Actually, yeah. And actually let me elaborate on that by referencing your first question about the age. I think the big problem with telemetry, with the use of the word ‘disease’ is not so much that we don’t call aging a disease. The problem is that we do call things like Alzheimer’s disease and cancer and atherosclerosis – we call them diseases. That is the mistake and the reason it is the mistake is because actually the difference between those things and the things that we rightly call diseases like infections is a much bigger difference, both in terms of the symptoms and the progression of the symptoms and the ways that we might be able to treat them. That is a much bigger difference than the difference between both of these, on the one hand. And the aspect with aging that we don’t call a disease – like declining function of the immune system or a loss of muscle or gaining of fat or whatever.

I think that if we are looking truly accurate and instructive, useful classification, if you like, of the various ways in which we can get sick then a much better one is to say that aging conflicts with everything that goes wrong with the body or the mind, predominantly for those people who were born a long time ago. And diseases are things that can affect young people just as much as older people.

[Damien Blenkinsopp]: Right, so the distinction – just to give some examples to the audience, would it be things like Alzheimer’s, Parkinson’s, even multiple sclerosis? I don’t think people tend to get that before the age of 30, for instance. Cardiovascular disease – would all of these kind of things be linked into that area?

[Aubrey de Grey]: Kind of, yeah. Certainly multiple sclerosis a bit of a gray area, whether you would really call it an aspect of aging – not just because it happens rather earlier than the other diseases you listed, but also because it certainly doesn’t happen to everybody. Whereas the diseases of old age, the commonest ones – whether it is cardiovascular disease, cancers, Alzheimer’s, these things tend to affect everybody at more or less the same age. Of course, some people die of one thing and some people die of another thing, but the only real reason for that is because of small differences in the rates at which different people accumulate the damage that results in these diseases. But most people who die of cancer die with Alzheimer’s in some level or other. Most people who die of atherosclerosis die with cancer. It is just that it hasn’t got so far along.

[Damien Blenkinsopp]: Right, so in your book The End of Aging, you describe the seven causes of aging. Would all of these be classified – would it be correct to call them some type of damage to the body?

[Aubrey de Grey]: I would call them damage, yes. In fact this is another kind of terminology question. I would say really that the best way to define the use of the word damage, in relation to aging, is that we would say that damage consists of exactly those changes to the structure and composition of the body at the molecular and cellular level that on the one hand arise as side effects of being alive in the first place, side effects of the stuff that the body does to keep us alive from one day to the next. On the other hand, they accumulate throughout life. They get progressively more and more abundant and eventually they get more abundant than the amount that the body is set up to tolerate, so that means they start to impair and eventually completely eliminate their physiological function.

[Damien Blenkinsopp]: Right, so there are clearly changes which take place because of aging, because of the processes that are going on as we are living.

[Aubrey de Grey]: I would say that they are aging, it is not so much by aging or they think they are aging, but the nature of aging is the changes in molecular and cellular structure.

[Damien Blenkinsopp]: Right. That is a nice way to put it because most of us think of aging as what we are looking at outside the body – the wrinkles and when you are looking at people you can see that aging. but in a respect we could say that the actual things you have defined and are changing within the body would be aging. so could you please outline what those are and which ones are the most important for you or if they are all the same? What is this kind of framework that you have and which ones are you most focused on currently?

[Aubrey de Grey]: The classification – there are seven major categories. It was really the big breakthrough that allowed me to see that the repair of damage was not only the most promising approach to combating aging with medicine, it was actually a feasible approach that could realistically be implemented within a matter of decades. If you have got 1,000 different things to deal with, then 1,000 different therapies are going to take a long time to develop. Well, if you can classify them into a much more manageable number of categories, such that within each category you are basically doing the same treatment for every example within the category and then the whole thing becomes much more feasible-looking, and that is exactly what I was able to do. So the categories are very simple things like having progressively-fewer cells in a particular organ or tissue because cells are dying and not being automatically replaced by the division of other cell. Or we accumulate molecular waste products in the cell because the cell is creating this waste product as a byproduct of something it needs to do. And the cell does not have any machinery either to break it down or to excrete it, so it accumulates.

Now, in each of these things we can look at and we can point to particular diseases and disabilities of old age that are predominantly caused by one or another of these things, so that is what we work on. And yes, we feel that all seven of these categories of damage are equally important. Certainly – well, there is one exception I guess, which is mitochondrial mutations where we can’t 100% certainly say it matters as much as the others. Actually, it might matter more than many of the others, we don’t know. But all the others we can say they matter pretty much equally as much because we can go into a particular nature, age, relation, or [pathology 00:11:42] and kill people at more or less the same age driven by that damage.

[Damien Blenkinsopp]: I see, so you are saying that pathology can be linked to each of these aging processes?

[Aubrey de Grey]: Yes, for example, molecular garbage inside the cell I just mentioned, that is definitely the reason we get heart disease, atherosclerosis – molecular garbage outside the cell is a major cause of heart disease in certain areas. Cell loss is the major cause of Parkinson’s disease, and so on.

[Damien Blenkinsopp]: Great. Thanks for that clarification. So you have outlined a roadmap to basically end aging and you have brought to light two concepts that I understand there are like bridges and there is something called longevity escape philosophy. Did you explain how these are eventually going to end aging or stop us from having to go through this process of aging?

[Aubrey de Grey]: Sure. So first of all, let me talk about bridges. That is actually not my terminology – that comes mainly from [Ray Kurzweil 00:12:40] who has often pointed out that there is a certain amount that we can do today to postpone the ill health of old age, and that is good. That is all very well. But there is actually more. Maybe we will be able, some of us anyway, to postpone the ill health of old age today with methods already available well enough to still be around in time for therapies that are not yet developed, because they haven’t yet been developed. If that can be done then of course we get an additional amount of life and we may be around for the next generation therapy, and so on.

And that concept – well, he normally talked about three major failures – what we can do today, what we might be able to do in the next couple of decades with our technology, and then what we might be able to do in decades after that using more of the non-biological solutions such as nanotechnology. And that is a fine way of putting it. Certainly the biotechnological approaches that he favored are pretty much identical to the ones I favor. And nanotechnology is certainly not an area in which I can claim much expertise, but I think he is more or less on the mark there, as well.

There are some where we part, actually, Ray and myself, as to how beneficial for most people what things are today, things that you can do already. And I think that [Bridge 1 00:12:40] as he calls it may not be much of a bridge, but by large the concept – we stand together on this concept. So the longevity escape philosophy, which you mentioned, is indeed from a phrase that I invented. And here I am not splitting the process of getting from here to indefinite longevity into that particular number of phases, like three – I am just saying that once we get a certain way along this process we are safe because we will be improving the quality and comprehensiveness of these therapies fast enough to stay one step ahead of the problem, essentially be repairing the damage that we couldn’t yet repair well enough that the overall abundance of damage will at no point reach a level that exceeds what the bod is set up to tolerate.

[Damien Blenkinsopp]: Right, and this relies on the concept that medical technology and biotechnology will be advancing exponentially?

[Aubrey de Grey]: Oh not at all and this is something which – and again I talk a lot with respect to I owe to information technology that we can see there is an accelerating track where progress is made at a faster rate as time goes on. In the case of longevity escape philosophy that may well happen, but the key point is it does not need to happen. In fact, if we are able to say 20 years from now or 30 years from now to reach this point where people are eventually not getting older, they are getting repaired as fast as they are aging, then it turns out that thereafter we can actually proceed at only that same pace and perhaps even slow down a little bit and will still be doing well enough simply because the rate at which the damage we cannot yet repair is accumulating will diminish as the types of damage that we can’t yet repair become fewer and fewer.

[Damien Blenkinsopp]: Great. Thank you for those clarifications. So what, for you, is the first and most important step? Right now are you really focusing – because you do funding of research and you kind of prioritize things – are you kind of prioritizing any of these steps in particular? Are you are trying to spread your investments so that you kind of manage the risk?

[Aubrey de Grey]: Very much the last, we are spreading. We have our fingers in all of these fires because we feel it is pretty stupid if we focused on some of them and then the other ones didn’t get done by us or by anybody else and people carry on dying on schedule even though most of the problems have been fixed. So we need to make sure, especially for the areas which are least fashionable, are being most severely neglected by other people, that it is vital for us to move forward. In fact, that is the only criteria that we use that really does determine what we choose to work on and not to work on. So the real manifestation of it is that we do very little work in stem cells. Stem cell work is very limited simply because so many other people are already working in that area. It is very burgeoning, very fashionable. So our work effort would be a bit of a drop in the ocean where we are the leading group working in many of the other areas.

[Damien Blenkinsopp]: Great, so basically you are choosing the least fashionable topics so that other things get pushed on it? And we actually do need to fix all of these problems. I mean, that is your assumption – in order to extend life and create longevity?

[Aubrey de Grey]: That’s right. I don’t think it is even an assumption, I think we know it.

[Damien Blenkinsopp]: Okay, great, great. So one of your other books looks specifically at mitochondrial mutations and the free radical theory of disease. Why did you specifically write a book about that topic?

[Aubrey de Grey]: Great question. So that was a long time ago. That book was published in 1999 and it is actually the only other book I have written. I have only written two books total. It was simply the first area that I got interested in when I decided I wanted to work on aging, whether it being to do something about it. Of course, I started out knowing nothing about that subject. In fact, I didn’t know all that much biology. I had been a computer scientist for my research career until that point. So I had a lot to learn. And obviously you learn some things before other things just by random chance. I ended up gravitating into the area of mitochondrial mutations as my main focus before I got interested in the other things.

So for the first few years of my career in gerontology in the late 90s, that was what I was working on and that was where I published my first half dozen papers or so. And my very first paper came to the attention of a publisher who did low print run academic books and said – anyway, what I wrote, so he said that he liked what I did and asked if I could go on writing a book, so I said all right, and that was the result. So the material in there covers pretty much my first three or four years or gerontology research. And it actually was also the [inaudible 00:19:08] idea was cemented to the University of Cambridge and I got the PHD for it.

[Damien Blenkinsopp]: Great. So would everything you wrote in there still be valid today or are there things you have discovered which you would change, some of that?

[Aubrey de Grey]: So the fantastic thing is that more or less everything is actually still true. There have been, of course, some minor discoveries that have changed things, but the broad sway of what I was writing there is certainly still true with one big exception. That big exception is exactly the exception that you like to have – namely, as time has gone on, new techniques, new ideas, and new discoveries have been made that essentially provide shortcuts – they have made the job of fixing this problem easier. And that is true also for the book that I wrote for ending aging, which is not nearly half as long ago as I wrote the mitochondrial and free radical theory book. So, they are pretty good, the lead idea of standing the test of time so well – the seven point plan that we work on is pretty much identical to what I was describing more than ten years ago or 12 years ago. So that is really circumstantial, but nevertheless quite strong evidence that we are on the right line, that there is more to this robustly standing the test of time.

[Damien Blenkinsopp]: Well congratulations because that is not an easy feat given how everything is changing so fast in biology and so on. So you have talked a bit about – one thing you mentioned earlier was except for when you are talking about the seven different areas and causes of aging, you said that mitochondrial damage may or may not be one of the most important ones. Why is there that area of uncertainty around mitochondria specifically?

[Aubrey de Grey]: Simply because there is no one major pathology we can point to where we can say clearly that there is a chain of events from this particular type of damage to that particular pathology. In the case of every other – the other six types of damage, we can point to a particular pathology and say that it is established. It is not even a hypothesis, it is actually known and absolutely agreed that the main driver of that pathology is a lifelong accumulation of that particular type of damage.

[Damien Blenkinsopp]: Great. So is that because we need to do more research to understand properly this mechanism in mitochondrial damage so we can say that we understand it less than the others?

[Aubrey de Grey]: I don’t think so, actually. I think the reason is the actual fact of the biology, rather than our understanding of the biology. I think it is possible that mitochondrial mutations simply don’t matter very much in aging, but it is more likely that they do matter but only by a very indirect route. And if it is indirect then it may be very placebic and it is something that affects pretty much all aspects of aging but in a subtle manner. So if you look at my book in 1999, you will see that there is some discussion of a rather elaborate mechanism – in fact, it is so elaborate that a lot of people just didn’t like it because it was too elaborate, which basically says that if mitochondrial mutations are accumulating even to relatively low levels, they may be able to be disproportionately toxic by essentially damaging molecules in the blood stream. And if they do that then those molecules can get into other cells and spread the damage around and kind of amplify it. This model is still very much a hypothesis and it has by no means been shown to be true, but it hasn’t been shown to be false either. And in fact bits of it, occasionally here and there, end up acquiring little bits of supporting data. There was a paper actually put out in [inaudible 00:22:54] just a few weeks ago, which was the first one to support one little technical detail of that hypothesis which previously had been completely controversial.

[Damien Blenkinsopp]: Great, great. It seems to me that mitochondria have become quite fashionable lately, just from my perspective. I don’t know if you would agree with that, when you are talking about the least fashionable versus the quite fashionable. There are a lot of supplements that tend to target more mitochondria and the word just tends to come up a lot more.

[Aubrey de Grey]: So yes, in a general sense mitochondria are very fashionable. Lots of people work on them. They have the major pre-eminent conferences on mitochondria that are bigger than ever, and so on. But the particular question of how we might be able to restore health to cells that have been taken over by mitochondrial mutation, that is obviously a very, very narrow area within mitochondriology and that is not fashionable at all. We don’t know, but we think it’s because people think it can’t be done. It’s a nature of science that people work on, things that they think they can succeed on and get published and promote and those things. And that means the hardest things often don’t get worked on at all.

[Damien Blenkinsopp]: Right, absolutely. So like Dr. Thomas Seyfried is well-known for his ideas around mitochondrial and metabolism and cancer. Do your ideas connect with his or are they different?

[Aubrey de Grey]: I don’t actually know that name. Tell me about this guy and his ideas.

[Damien Blenkinsopp]: With the metabolic theory of cancer?

[Aubrey de Grey]: Okay, there are various metabolic theories of cancer, but go on – tell me the ideas a little bit and I will tell you what I think of them.

[Damien Blenkinsopp]: Well, the idea is basically about free radical damage of the MT DNA and once that is damaged the mitochondria are not functioning so they are not giving sufficient energy to the cells. The idea is that from there the cells start behaving in a different manner, which includes cancer.

[Aubrey de Grey]: All right, so certainly stated that simplistically that theory is not correct. Variations of it –

[Damien Blenkinsopp]: I am sure I am not doing it justice at all.

[Aubrey de Grey]: Variations on that idea may have some validity. Certainly we see in aging that normal cells that are not cancerous at all accumulate mitochondrial mutations. Only a small minority of cells do that, but the ones that do get completely taken over by that mutation. In cancer we don’t see those same mutations. We do see some mutations sometimes and certainly one thing that we see much more ubiquitously is a depression of mitochondrial function even in the absence of any actual mutations. So the [inaudible 00:25:36] and we certainly have a number of theories out there that describe how cancer cells may obtain some kind of advantage then and protect themselves from the immune system, for example, by doing things like that or reducing their oxidative metabolism. So if that is the general theory that is being put forward, then yes, there is a certain amount of validity to it. But the thing that counts is that there are an awful lot of ways this can occur. There are an awful lot of ways that cancer health can discover to escape the normal controls that stop cells from dividing when they shouldn’t. So they have to do a bunch of things like breaking down the intracellular matrix, they have to ignore the signals that tell them not to divide, they have to ignore signals that tell them to die. They have to, as I say, resist the attack from the immune system. All of these things are really hard and any cancer that has reached a size where it has come to the notice of the clinician it has already jumped through a million hoops. So there are a lot of different ways to be that way.

[Damien Blenkinsopp]: Great, thank you. So today we have a lot of things in the press – there are a lot of products and there is a fair amount of research around topics which supposedly could help to give us longevity. Some of these are caloric restriction and linked to that fasting, autophagy, mitophagy and then we have the telomeres, telomerase and some others. For any of these things that are available today, and we can stop and look at them separately, I understand that you feel that none of them are actually targeting any of the seven areas, or any of the seven causes of disease sufficiently to actually extend our life. So could you talk a little bit about why you feel that is? Perhaps you want to tackle the biggest one, which is caloric restriction, for example?

[Aubrey de Grey]: Yes, by and large the simple approaches that we have today are not even hypothesized to actually repair damage the way that science is trying to do. So the best that could be said about these things, the proponents will say, is that they may slow down the subsequent accumulation of more damage. So that is still good. That means you are postponing the age at which the damage reaches an abundance that is insupportable, but of course the later you start the older you are when you start doing it. And then even if it works, the less benefit you are going to get because you have already accumulated all the damage at the original rates. So that is bad enough, but yeah. So you can say I am also very pessimistic about the ability of the approaches even to slow down the accumulation of damage by a meaningful amount. In very short-lived species calorie restriction is very effective. We can certainly increase the lifespan of a mouse from let’s say two-and-a-half years to three-and-a-half years using calorie restrictions, and that is pretty impressive. But if we go further down the evolutionary chain and we ask about small invertebrates like worms, for example, that normally live only a few weeks, it turns out that calorie restriction can do a great deal more. You can multiply the longevity of a worm by a factor of maybe three or four by calorie restriction.

The unfortunate thing is that this correlation, this inverse correlation between the natural span of the species and the extent to which that lifespan can be multiplied by calorie restriction works the other way as well. So 20 years ago people did a calorie restriction experiment on dogs and they only got a 10% increase in lifespan instead of the 40% that you might get in mice. And more recently we had a couple of experiments that on for more than 20 year looking at monkeys under calorie restriction. They finally reported and they got less than 10% – in fact, one of them was basically faster. So it is not looking too good. The worst of it is that this is what we should have expected because it actually was predicted by evolutionary theory – especially simply because long famines are not so frequent as short famines. We are unlikely to have the ability – to have evolved the ability – to respond to long famines in a manner that would increase our evolutionary fitness whereas short famines we experience frequently enough irrespective of how long the actual lifespan is that it makes sense to have that ability.

[Damien Blenkinsopp]: That’s great. And of course, currently the more fashionable topic around caloric restriction and fasting is intermittent fasting, which is typically anything between 18 and 24 hours for most people. Do you have a different view of that and the idea of this, which is activation of autophagy which can help to clear up some of the cellular garbage?

[Aubrey de Grey]: No, it is absolutely the same. The kinds of metabolic changes and expression changes that are induced are basically identical, and a good approximation – whether you have continuous calorie restriction or intermittent fasting or whether you use drugs that essentially trick the body into thinking it is on calorie restriction when it isn’t like [rapamycin 00:30:59] or whether you use genetic modifications in model organisms that trick the body in that way, by turning on the same pathway. It is no surprise. All of these things are turning on the same response, they are just turning it on in different ways. So of course you are going to get the same response.

[Damien Blenkinsopp]: Great, thank you very much. So the other big area – I guess you could tell me if you see this as the other big area because you do a lot of these interviews and you probably get the same kind of rejections. I think the other big area is telomeres and telomerase, which has become very fashionable now. And I understand that of course you think that isn’t an area that is going to help us?

[Aubrey de Grey]: Sure, so the telomere is a critical part of the cell and the organism and we definitely need to understand how it changes with aging and the extent to which those changes are good or bad. But we definitely cannot say at this point that the changes we see during aging are uniformly bad and therefore the thing to do would be to stop those changes from happening. The reason we can’t say that is because it seems that large animals, or large mammals and certainly humans, have made use of the telomere as a kind of way to get a tradeoff – get the best of both worlds between two important aspects of aging. One of them being the inability of the cell to – well, let me back up and say it a little differently.

One of them being the increasing inability of cells to divide and the other being the increasing tendency of cells to get into a state where they divide when we wish they didn’t. Most of our cells, let’s remember, do not divide – or if they do, they only divide fairly rarely, on demand. Like, for example, skin cells – the bottom layer of the skin that divide like crazy when you have a cut, to close the wound. It is only a small proportion of our cells, a few cell types, the stem cells of rapidly renewing tissues like blood which divide regularly. Those are the only cells that have a potential problem of telomere shortening.

Telomere shortening is something that happens when cells divide because of the nature of DNA replication and eventually when cells have divided enough they end up getting telomeres that are so short that bad things happen in the cell. I won’t take the time to go into what bad things, but the cell basically gets unhappy.

So cells that divide rapidly need to compensate for this and they have an enzyme called telomerase which does so. They certainly don’t need that capacity because they don’t divide often enough. They just don’t make the same amount of telomerase. Now, most people believe that the reason why they don’t make it is so that if they mutate, or become cancerous, then the cancer will not be able to grow large enough to kill us because that will require enough cell division that the telomeres will get short and bad things will happen to the cancer cells and the cancer will just wither away. So the question is if we want to do better than what evolution has done, how do we address this tradeoff?

One way might be to make most of our cells create more telomerase, more of this enzyme. That would allow cells in the blood, for example, to divide more than they currently do. And that would be interesting because it might make the blood continue to work better and the gut continue to work better, and so on, but it would run the risk of exacerbating cancer. The alternative is to go the exact opposite direction to bear down on to telomerase and make it less of it. That might be a really good way to suppress cancer but it might exacerbate the more degenerative aspects in that it makes our blood age faster, for example. We simply don’t know which of these factors is going to better because really it is not just which of those things you do, it is also how you cope with the side effects that you are creating. You are going to make one or other sides of the equation worse, you have got to find some secondary therapy to alleviate that and we of course don’t know yet.

So a number of people are working on the telomerase stimulation side of the equation, going to rescue the aging of dividing cells by giving more telomerase and then trying to find some other way to deal with any cancer problems that might arise. And we are going the other way and saying we are still with cancer by suppressing telomerase and left the other cells to deal with the cell division problems that might arise.

[Damien Blenkinsopp]: Right. And that seems to be because cancer is one of the most sure things which is actually going to kill us versus the other side of the equation, which you are saying is more of a functional impact rather than a kind of end of life kind of impact?

[Aubrey de Grey]: Well, I wouldn’t quite put it like that. I mean, there is still the big question of the extent to which telomere shortening really contributes to the pathologies of old age, so definitely telomeres get shorter in the blood in older people, but nobody has really been able to show they get so short they cause loss of function. So we actually may not need to worry about that in a currently normal lifetime But for sure, if we were to suppress telomerate in the manner that I have been talking as an anti cancer therapy, then we would create a problem even if the problem doesn’t already exist.

[Damien Blenkinsopp]: Right – when we are dealing with really complex problems it has been shown that can often be the case for therapies. So a key thing we talk about in this podcast is any aspects of quantification and with respect to longevity I am wondering if there is anything that you feel that is worth monitoring to track how we are aging? Now, currently it is fashionable with telomeres to measure the telomeres and they have indexes which say your telomeres versus someone else your age are above average or below average in terms of how many you have left, basically. Are there any biomarkers that you feel can validly track the progress of aging and perhaps how it varies between different people based on their lifestyles, their genetics, or any other factors that might be affecting the rate at which they age?

[Aubrey de Grey]: That is a really tough question. They don’t actually age, the Natural Institute of Health paid a huge amount of money several years ago, many years ago now, into a long-term study trying to identify biomarkers of aging that were really reliable and it was basically completely unsuccessful. They basically found nothing. Now, people haven’t given up on this but the reason they haven’t given up is the complexity. Essentially there are a couple other things you can die of, so how do you put aside whether one means by a biomarker of aging. Well, you have to define that some how, its another way of saying the predictor of how long you are going to live, what your remaining longevity is, or that you will remain in healthy longevity, but then you have to define health and it gets a little bit fuzzy as well. So it is actually quite hard to even define what you mean by biomarker of aging, but even once you have gotten past that difficulty, because there are so many different things that go wrong you don’t expect to have one simple or even fairly simple number that says something like this.

You expect, one would think, that as you get older you are as old as your weakest link. So you are going to expect that you would want to measure a lot of things and each of them points to a probability of getting a severe case of this or that type of age-related pathology in this or that amount of time. And certainly some things are more influential than others. These things affect each other and we may be able to point to things that are a bit more indicative overall of the probability of death or disease of all types in old age. But it is a very – it is not an exact science, put it like that. I have been lucky enough to have my biological age tested, which I have been able to do maybe four times now over the past decade or more. The test I have been able to get done on me involved measuring probably 150 different things in my blood as well as all manner of physiological and cognitive tests. There is no one number that comes out of that, really. There is no one useful number. The only thing that really usually comes out of it is what to pay most attention to, what seems to be changing more rapidly or seems to be problematic levels or that of other people of your own chronological age, those sorts of things.

[Damien Blenkinsopp]: Right, so there are 130 markers. Would many of those fit within your seven areas of damage and kind of be related to that?

[Aubrey de Grey]: Oh certainly. Certainly not now because the things that one measures in the blood aren’t metabolized. These are small molecules that are constantly being ingested into the body or synthesized by the body or destroyed by the body or excreted from the body. The blood stream is just this pipeline, right? It is just this network of roads that take things from one place to another and particularly it shortens molecules whereas the seven types of damage that I talk about, types of molecules or cells, the molecular or cellular changes that accumulate over time. So in other words, yes, the concentration of a particular small molecule in the blood may change but that is because of subtle changes in the set point, in the equilibrium between synthesis and destruction or ingestion and excretion of those molecules, which are kind of readouts of the level of damage elsewhere – maybe of the activity of enzymes or the activities or numbers of certain cells, for example. But they are not the damage itself, they are readouts of the damage.

[Damien Blenkinsopp]: Okay, great. So if we wanted to live longer today – I mean, I know one answer which we are going to definitely come up with at the end which we need to talk about, like helping you fund the different areas because you see that as the most important to targeting these areas that we are not really looking at – but for the people at home who are concerned about their longevity, what would be the best strategy for them in terms of thinking about their own health?

[Aubrey de Grey]: I wish I had a better answer to this, I really do. Certainly I know that there are some people – if you are an unlucky person, so Ray Kurzweil – come back to Ray Kurzweil again because of course he is well-known as someone who thinks that one can make a big difference to one’s longevity using supplements and so on. He probably is making a substantial difference to his own longevity that way, but that is because his own longevity by default was probably going to be rather shorter than average. He has a lot of cardiovascular disease in his family, he came down with type 2 diabetes in his 30s, which is pretty unusual even though it is not unheard of. And he has been able to really completely fix that using his regime that he developed himself and I totally applaud that. What I can’t do is say that this would apply to people who are already doing okay, especially those doing better than average, like me. Only if you are somehow unlucky, we have simple ways that may be able to somewhat normalize your rate of aging. Now, of course, on top of that, there is the fact that there are plenty of ways to substantially shorten your longevity by smoking or getting seriously overweight or eating a very poor diet, for example, but you didn’t need me to tell you that. I bet your mother told you.

So unfortunately over and above that, as things stand, we cannot point to anything that can appreciably help most people. And that of course is why I always say the only thing you can really do is buy more time – not by extending the time that you stay healthy but by reducing the time before therapy had come along that would actually do much more than anything that exists today.

[Damien Blenkinsopp]: Right. So I will kind of run by you the way I think about this and see if you have ideas on this, to see if this is a decent idea or not. The way I talk to my friends and stuff when they ask me these kinds of questions is I say that basically you want to manage your biggest risks, right? So if you were talking about Ray Kurzweil has cardiovascular risk in his family. For instance, you had a 23&Me or other set of genetic tests which point out that with some probability you have – for instance, I have a higher risk of lung cancer than most people and a couple of other things in my profile and people have different risks. So I suggest they look at that and then potentially they look for the biomarkers related to that on an ongoing basis rather than the genetic longer-term risk. And they monitor that and they also look into the things that can reduce that specific health risk and to reduce the risk and to limit the risk of them actually getting that biggest risk. So it is kind of plugging the biggest gaps they have of shortening their lifespan. I am just wondering if you think that is a reasonable approach?

[Aubrey de Grey]: For sure. I think in general for most people if you have got a risk factor that puts you at risk of being considerably shorter length than average, then you are going to know about it as a consequence of the kinds of metabolic tests I was talking about. But there can certainly be exceptions to that, things that truly don’t really affect your health as measured in normal ways, so that is all they do. Like suddenly some of them bite you in the backside. So that is the kind of thing that 23&me analysis might lower. But one also has got to be extremely careful in evaluating that kind of data because ultimately it arises from basic science. It arises from people studying particular genetic variations in the population and identifying correlations between those variants and the instance of this or that to these. And those studies are notoriously difficult to do and they have a notoriously low level of reproducibility because different populations are different and because sample sizes are limited, and so on and so forth.

[Damien Blenkinsopp]: Thank you. I always appreciate your answers because they provide a different context and perspective to everyone else so it is always very interesting to get that feedback. Let’s talk a little bit about SENS organization and what you’re up to there because this is your vision basically for making it happen. So you have different activities – and I also want to know a little bit about the [Methuselah Foundation 00:45:56] which you were formerly part of. And I understand that has some similar activities although it is going about it in a different way.

[Aubrey de Grey]: Sure, and let me actually start with the Methuselah Foundation because that makes more sense chronologically. The Methuselah Foundation is a charity, a 501-C3, that was created by myself and a businessman from Virginia named David Gobel in 2002, late 2002. Our goal was, of course, was to hasten the defeat of ageing but we didn’t have any money. So we started out creating a prize pot creating competitions in which we encouraged people to give up money that would go into a prize box and that the competition would be to beat the prevailing world record for mouse longevity. So with all you had to do the mouse that lived longer than any mouse had ever lived before. And of course we weren’t saying how things would be done and we set things up so that even a small improvement would be enough to win some proportion of the prize box. And it worked.

Basically our goal was to raise the profile of longevity research to get the word out and to get people more interested in the possibility of developing medicine to postpone ill health of old age. Well, we were bringing all this money in and right about 2005 or so we had enough money that we felt we could spend some of the prize pot in advance on actually pursuing specific research projects. So that is what we started to do and then things started going pretty well in that regard. But then we had a problem which we started to recognize in about 2008, which was that if you are a research organization you have got to obviously impress people with your competence and you have got your feet on the ground and everything like that and you are doing the right stuff. Well, if you are a PR organization, to get people motivated and so on, then you want to be the opposite – you want to be very popular, sensational, and glitzy. So we felt that it would actually serve the mission better if these two themes of our activities were between two different organizations, which would thereby be able to have very different styles, discourse, and styles of communication. So that is why we created the SENS Research Foundation, which was started in 2009.

SENS Research, of course, is also a charity – a 501-C3 so anyone can get tax back. And because this is going out internationally I should probably mention that we have a subsidiary in the UK which is able to take tax-deductible donations not only for UK citizens but also from most of mainland Europe. And if anyone wants to know about that they can contact us on the website and we will tell them more.

[Damien Blenkinsopp]: Thanks. We will put all the links in the show notes.

[Aubrey de Grey]: Excellent, thank you so much. So we created the SENS Research Foundation and it has been a truly, and the Methuselah Foundation and all the assets that have been given us research into the new foundation, so both foundations have been made in parallel since that time and I think we have both done pretty well and it is pretty good. So SENS Research Foundation, to go into a bit more detail – we are headquartered in Mountain View, California, just a little south of San Francisco. We have about 5,000 square feet of space in a facility, most of which is lab space. We have a variety of projects going on here. We actually have more than two-thirds of our research budget is not in our facility but rather in five university labs, again most in the USA, but some elsewhere. We have on outside Cambridge, Biotechnology Institute, and these projects are focused on all of the various areas of research there that SENS describes.

[Damien Blenkinsopp]: Yes, and I don’t think we have actually said what SENS stands for – Strategies for Engineered Negligible Senescence.

[Aubrey de Grey]: That’s right. We don’t often try to spell that out because it is a bit of a tongue twister. The name originally arose because of – well, basically historical reasons within gerontology. The phrase ‘negligible senescence’ already had a particular technical meaning and it seemed like a good place to start. But it is a bit of a tongue twister so we don’t bother to get people to remember that anymore.

[Damien Blenkinsopp]: Great, thanks. I will put links to all of those, of course, in the show notes. One last thing I just want to ask you, Aubrey, is from a personal stance you have said every few years you are going to test 130 markers or so of your own. Are there any specific things that you feel are important for you to personally track about your body for longevity, health, or performance?

[Aubrey de Grey]: Well, yeah. I mean, I think that first of all, coming back to something that we were talking about earlier, if any one marker is out of whack, you know, it seems like it is really telling a much more pessimistic story than the rest, then you have certainly got to try to ask yourself why, ask yourself whether it really is an outlier, whether it actually has that much impact given everything else as people say, things like that – but it is definitely not something that would be a good idea to ignore. So my one outlier the past couple of times I have done this kind of thing has been homocysteine, and I have no – I am not really sure why my homocysteine level is unusually high because everything else that it is supposed to interact with has not – but it is still something that I pay attention to.

From that, I can certainly say that there are certain things that are really at the nexus of metabolism, things that really if they are extremely good then you will be pretty safe, pretty much with whatever else is happening. Insulin is the best one. And of course, insulin is the hormone that mediates the absorption of sugar after you eat a sugar-rich meal so that the overall concentration of sugar in the bloodstream is maintained at as constant a level as possible. And the precursor of diabetes, type 2 diabetes, is something called insulin resistance, where the cells that take up sugar in response to insulin, which are mainly muscle cells, start to be a little sluggish about it and to only respond when they are given a large amount of insulin. So if your insulin is high, then even if your glucose tolerance, as it’s called, your ability to normalize your glucose in the blood is still good, then the indication is that it won’t be good for very long. Whereas glucose tolerance is good and also your insulin is really low then that says that you are in the best possible state. I would say if you have one thing, that would be it.

Perhaps another one would be triglycerides, whether it is a type of fat which seems to be good to have very little of in your blood stream and again, I am pleased to say that I do.

[Damien Blenkinsopp]: Thank you very much because those are basically the biggest diseases that we have today, like metabolic syndrome, so those are good markers for that. I guess one of the confusions with biomarkers we are always facing is that we are not sure if it is the end point. So one last question I did have for you was on a Palo Alto longevity prize. I am not sure if you know about that?

[Aubrey de Grey]: I certainly do and I am invited to it.

[Damien Blenkinsopp]: Oh, great. Because I understand they are running a competition or they have been running a competition for heart rate variability in connection with longevity.

[Aubrey de Grey]: That’s right, yes. So, businessman in the Bay Area in Joon Yun has put up a million dollars as a prize fund for progress against aging. It is divided, actually, into two separate prizes. One of them is looking specifically at heart rate variability, as you say, but the other one is a bit more general. It is looking at what they call homeostatic control or something like that. I forget the exact terminology. But the point here is that the competition is for the attempt to actually extend longevity [inaudible 00:54:06] in this manner. And I think this is great. I mean, the heart rate variability aspect is a bit unusual for people who have not really bought into the idea that this could be a real fulcrum of aging but it might be. And we think it is great to encourage research in any area that hasn’t been terribly well looked at. The main thing is simply putting a million dollars on the table as a great way to get people pretty excited, and a lot of people are paying attention now, especially since in the Bay Area there is a lot of identity of people interested in longevity in general. It’s a great way for a research foundation to be located. So yes, I absolutely applaud them for doing this.

[Damien Blenkinsopp]: Great to hear you are part of that also because we had heard of that from one of our previous guests. Aubrey, thank you so much for your time today. I love to hear all your different ideas of course because you are working at a very high level compared to most people, so you have this perspective that stands back a bit, which can be very helpful to people. Thank you so much for your time and have a great day.

[Aubrey de Grey]: Thank you, and to you. Bye.