Alright, thanks for that. Pretty well actually. Thanks for coming. I have no idea why I'm first up, right now, because my talk doesn't really fit that way, well I don't think it does, but we'll see, we'll see. Thanks to Alex, by the way, for organising this - I'm really impressed at the ability that everyone has shown in putting all of this together, and I'm enormously looking forward to the next couple of days. So the talk I'm going to give, since I know a lot of you are familiar with quite a lot of my work already, is one that I gave just a few months ago for the first time at the Singularity Summit, which was a sufficient number of thousands of miles away that I'm hoping that most of you didn't see it. It's not all that long, so I hope I'm able to get done in time. Essentially what I'm going to do is offer a few perhaps slightly novel thoughts about the relationship between a concept that I'm sure all of you are familiar with - the technological singularity - and something that was actually given its name a couple of years ago not by me, but by a friend of mine, Paul Hynek - who lives nearby actually - Paul, you're not in the audience are you? - called the Methuselarity, which I will come to in a few seconds.

I'm the chief science officer of SENS Foundation, a U.S. based charity, and we're interested in doing something about aging, and the way we're going about anti-aging is essentially to promote and fund and pursue the various approaches that I have been promoting over the past 10 years or so, which essentially come down, in a nutshell, to the application of regenerative medicine to the problem of aging. So in other words, I'm focused very much on reversing biological aging, on repairing the accumulating molecular and cellular damage in aging, rather than on merely slowing down its progression. I'm going to spend a few minutes, for those of you who are not familiar with what I do and haven't seen me speak before, a few minutes summarising the logic here, summarising of why that seems like an interesting way to approach the question, and why it's foreseeable that we might be able to make some big progress in that respect in the lifetimes of people in this room.

We'll start off with this. I've been saying for some time that we need to think properly about what aging is. Not just correctly, but in an appropriate way that is conducive to understanding how to think about postponing it. And I like this definition, which says first of all something fairly obvious, namely that being dead is a consequence of being alive, in other words that the types of damage that accumulate in the body and eventually cause the pathologies of old age are simply side-effects of normal metabolic processes that are necessary to keep us alive from one day to the next for as long as we do succeed in staying alive. The important thing on this slide is that we can identify a set of intermediates between metabolic processes and the ill-health of old age. I use the word "damage" to denote these intermediates. The things that I am calling damage for the purpose of this definition are the immediate side effects of metabolism, the things that metabolism lays down all the time, even starting before we're born, and that accumulate throughout life, so that the composition of the body at the molecular and cellular level gradually changes, and eventually those changes start to get in the way of metabolism and cause the problems of old age that we want to address. The reason that's a useful definition can essentially be communicated by showing you how the two paradigms for doing anything about aging that have historically been followed relate to that definition. So I've got the definition down here, metabolism causes damage causes pathology, and there are these two approaches to addressing that. The geriatrics approach essentially says concentrate on old people - it says let's look at these pathologies and try and catch them as they are emerging, and slow down their rate of progression, so as thereby to postpone the age at which the pathologies reach a life-threatening stage. The gerontology approach says well, hang on, prevention is usually better than cure, why don't we try and get stuck in earlier in the chain of events - why don't we try and in some way clean up metabolism, so that the various types of damage that metabolism creates are created more slowly than normal, and therefore, again, we will postpone the age at which pathology starts to emerge. And that's all very cool, except that they've got a couple of problems. This is the problem with the geriatrics approach. The chaos of aging is really very considerable. And of course the big deal here is that it really is intervening too late in the game. The concept of the geriatrics approach is that we address the pathologies of aging directly. But since the causes of those pathologies, the precursors of those pathologies, are continuing to accumulate throughout life, because those precursors are the things I'm calling "damage", then obviously the problem is getting harder and harder for the geriatrician to address. So the geriatrics approach is better than nothing, yes, but it's not much better than nothing. And for that reason, it really in principle never will be, never can be much better than nothing. So that's all very well, we still have geriatric approach. Unfortunately, as every biologist will attest, the fact is that metabolism is rather complicated. And of course this here is a simplified diagram of a small subset of what we know about how metabolism works, but that's not the problem. The problem is that this is a small subset of what we KNOW about how metabolism works, and it is completely dwarfed by the astronomical amount that don't know about how metabolism works, even completely ignoring the even more astronomical amount that we don't even know that we don't know. So really it's basically hopeless: there's no way in hell that we're going in the foreseeable future to be able to manipulate this network, this system, in a manner that does not do more harm than good. Most of the time, when we try to affect metabolism by supplementing with anti-oxidants or whatever, metabolism just laughs in our face and gets on and does what it was doing anyway, it just compensates, and the rest of the time, when we do actually make a difference, the chances are, as I say, that we do more harm than good. So this is not a promising approach either, at least not yet - in the long term, maybe, but not yet.

Alright, so, what's the catch? Why can I be optimistic about aging? Essentially I'm optimistic because I think there's a third approach. We should always remember, of course, that the human body is a machine - it's a really really complicated machine, but it's still a machine - and therefore that methods that we use to maintain the health of simple, man-made machines beyond their warranty period so to speak, may in principle give us some information about how we could extend the lifespan of the human body beyond its warranty period. And I think in this case we can indeed learn such a thing. Here's a car that was built to last, with lovely corrosion-resistant metal, and tough tires and all those good things, and sure enough it's more than 50 years old, whereas your average car doesn't get much beyond 15 years before we junk it and get a new one. This is the automotive analog of the human body, as compared to the body of a dog, or a mouse, or any other species that doesn't live so long as we do. We are built well in the first place - we have really really good in-built, automatic anti-aging machinery, and the only reason we age at all is becaues that anti-aging machinery is not comprehensive. Alright then, so why do I say "VW Bugs" up there? Very simple - it's because, of course, there are just as many 50-year-old VW bugs driving around the streets of the U.S.A. as there are 50-year-old landrovers. And the reason there are is NOT because they were built to last. They were built no more robustly than your average car. The reason they're lasting so long is because they've got style, which has caused their owners to fall in love with them and do an exceptional amount of maintenance on them. These guys get maintained a lot better than they legally have to, and that's why they keep going a lot longer. These, and of course corresponding examples like first-world-war aeroplanes, are examples that show that maintenance really works. Maintenance can, actually, if it's comprehensive enough, extend the functioning, healthy lifespan of a machine way, way beyond what it was designed for. So if we come back now to the human body, and we say, well, what does that actually mean? - well, what it means is this: there is a third approach. Let's call it the maintenance or engineering approach. And I claim that this approach has a lot better chance than the others of actually making a difference here. Because the fact is, it avoids the problems I was mentioning earlier. It avoids the problem of the geriatrics approach, because it's intervening early enough in the chain of events that it doesn't have - the target of the maintenance approach is not a consequence of something that is accumulating. By definition, damage doesn't have any accumulating precursors. And the idea, of course, with the maintenance approach is that if you're removing that damage after it's been created but before it's got to the point where pathology starts to result from it. The maintenance approach also avoids the shortcoming of the gerontology approach, because the key point here is that we do not require to slow down the rate at which damage is created. We only get rid of the damage AFTER it's been created. The concept here is that we are effectively side-stepping our ignorance. We can get away with not knowing very much about how metabolism works because we aren't proposing to actually interfere with it. The target of the maintenace is the set of initially harmless, initially inert consequences of metabolism that only become problematic after they've accumulated to a certain level of abundance. Because they are initially inert, they are if you like not participating in metabolism. So if we target them, then we have a vastly better chance than we do with the gerontology approach of getting what we want without causing unintended side-effects.

So of course the really good news is that I think we know how to fix all these things. I'm certainly not going to try and go through all of this today, because it takes forever and I wrote a book about it anyway, so if you haven't got the book it's your own fault. But the short story is that we're pretty close to actually implementing not just ways to slow down these various types ofthat I normally divide into these seven categories, but also actually reversing those things. Stem cell therapy, for example, is basically the way that we're going to address the problem of cells dying and not being naturally replaced by the division of other cells; some of the things down here are a good deal harder and that's why we can't do them yet, but we're getting there, and he hardest things are the things that my foundation tends to emphasize, because we don't want them left behind.

So the key point that I often make to audiences like this is that, even though the therapies that I just put up on the previous slide are foreseeable, that won't be the whole story. They will probably only succeed in postponing the pathologies of old age by maybe 30 years. They will be comprehensive, but not totally 100% comprehensive. Now, 30 years is nice, but it's not defeating aging. But the really good news is that because we will be rejuvenating the body, actually repairing the damage of old age, we are going to be buying time. And of course what I mean by that is that we have time to improve the quality of the technologies. So on this really rather ugly and schematic graph, what I'm showing is the concept of normal aging on the red line, which is simply the accumulation of damage during life - we've got age on the x-axis. On the y-axis I've put "reserve" - all that means is the inverse of damage, the amount of damage that you can afford to accumulate on top of what you've already got before problems start to happen. So this is aging, you start off at age zero with lots of reserve, not much damage, damage accumulates, eventually you hit this dotted line, the fraility threshold, where pathology begins, and then there's not much hope for you. The pink line is what I've told you so far, where you take someone in let's say middle age, you fix them up reasonably well, not perfectly, because we don't know how to fix everything, but if we can fix them up reasonably well then we've bought some time. They carry on aging at the normal rate, because as I mentioned, we're not trying to slow down the rate at which damage is created. And then we can apply the therapy again and again and again, and that's why we get this nice increase of maybe 30 years. And the problem, of course, is that we only get that long, because we hit diminishing returns. We hit diminishing returns because the types of damage that the therapies are not successfully getting rid of are continuing to accumulate, and eventually on their own, they are enough to push the individual over the frailty threshold. But if we now take into account the fact that repairing damage buys time, we see that the situation is a lot rosier. Because the interval between the first two applications of these therapies applied to our hero over here is maybe 15 or 20 years, and that's one hell of a long time in technology, including biomedical technology. So what that means is that when this guy comes in for his or her second rejuvenation, they won't get the same therapies as the first time or second time, but a new set of therapies that repair the other types of damage. The results are qualitatively different. Not only are they more rejuvenated, they won't get the same therapies they got the previous time - they'll get improved therapies that can fix not only all the easy types of damage but also some proportion, let's say half, of the difficult types of damage. And as you can see, the result is qualitatively different, in that this person is not only more rejuvenated than they would have been with the old therapies, they are actually more rejuvenated than they were the previous time, even though they are chronologically older tan last time. And if ew iterate on that concept we can see that over the long term the individual is getting biologically younger as they're getting chronologically older, which means that they can avoid the ill-health of old age indefinitely, however long they live. So of course there is some sort of cusp here, some sort of minimum rate at which we need to improve the comprehensiveness of the therapies in order to actually deliver this indefinite life extension that we would get from this, and that's the thing that I have been calling longevity escape velocity. It's of course rather wordy if you write it out like this, but ultimately it's a very simple concept, as you can see - the rate at which the repair and maintenance therapies need to be improved in their comprehensiveness, following the achievement of that first thing that I call "robust human rejuvenation" that will give us maybe 30 years, in order to stay one step ahead of the problem. Simple idea, and that's what it is. Alright, so, a couple of years ago, as I mentioned, Paul Hynek decided that it was appropriate to give a name to the point where we reach longevity escape velocity. And he noted that there's a lot of conceptual similarity with the technological singularity, so he said let's call it the Methuselarity. Some of you know that I started a charity about seven years ago called the Methuselah Foundation; that's where I used to work until April of this year; in April we started a new foundation called SENS Foundation, to which the Methuselah Foundation divested all of its research activities, and the Methuselah Foundation is now back doing more or less what it was doing at the beginning, namely focusing on the mouse longevity prizes that we rather successfully used as a public relations exercise to raise the profile of all this work. But we have found that it is actually more effective to do research in a separate organization, and that's what we're doing now - ask me more about that if you really want to know.

OK, so, the methuselarity, that's what it is. Are we going to reach longevity escape velocity any time soon? I reckon we peobably are, because if we look at the rate of progress in developing technologies then we see that, even though it's very hard to predict the achievement of fundamental breakthroughs like powered flight, it's rather nice when we look at what happens after that, with the incremental refinements of those breakthroughs - they tend to happen rather smoothly and rather rapidly, just until public and commercial pressure and so on starts to diminish as it did around 1970 when it came to improving powered flight and not delivering flying cars. We also did a nice simulation a couple of years ago to look at what would happen with aging. And we found this, which is the rather good news that we can reach longevity escape velocity very easily - I won't go through the details of this graph, it'll take me too long - but we can do it even if we are really really slow in improving the comprehensiveness of these therapies -I mean that's a ridiculous amount of time, that's the time between Lindbergh flying across the Atlantic and Concorde being launched for the first time. Alright, so, what are the differences? Well, of course the singularity is all about accelerating change - it's all about things spiralling upwards and upwards. The Methuselarity is rather the opposite if you think about it, because we're actually looking at a situation in which we are diminishing the rate at which people are getting older. We're trying to preserve things as they already are. Which is a little bit of a contrast. But maybe we can think, well, OK, we're going to hit diminishing returns in the sense that it will become harder and harder and harder to knock off more and more of the really really difficult types of damage that happen in aging. Well, it turn out that even that's probably not true. If we look at what's necessary for longevity escape velocity, it diminishes with time. Here I've got the same graph as before, except that what I'm saying is the second time you get these therapies, you only actually knock off a third of the damage that you couldn't repair 20 years previously, and the next time only a quarter, and so on, and you can still see that it's still good enough. So it really looks very different. And of course, here's a car which proves it. This car is 100 years old, and it's not getting any more maintenance than what it was 20 or 30 years ago, when it was only three or foir times as old as it was designed to live to. So hat's why I think we'll be achieving 1000-year lifespans really rather soon. So what we've got here is a really very interesting thing. In terms of the functionality, the actuality of what the machines can do, the singularity is the dramatic thing - machines get exponentially more intelligent and more capable per unit time, whereas for the Methuselarity we can actually slow down the rate of progress. But in terms of the human impact it's actually the other way around. In the Singularity we'll be taking machines which will already, before we reach human-level intelligence, be really hardly computers at all in terms of how we use them - I mean, most of you who have been using computers for the past 30 years probably already think that computers of today are not really computers - wheareas for the Methuselarity we will go from this very gradual increase of longevity up to indefinite longevity just like that. So it's very interesting, and i think there's a potential for synergy here. One big thing is that we die of other stuff. At the moment, 1/3 of all deaths in the world, and 10% of all deaths in the industrialised world, are due to things other than aging. We probably won't be terribly keen on that when we don't have to worry about aging any more. ASnd the thing is that when we've got all these machines that the singularity is going to give us, we're going to have rather a good capacity to avoid death from any cause, including aging, but also including all the other things that we die of at the moment. I mean, it might take a few more decades, or even 100 years, to really prevent asteroid impacts, but I bet it won't take more than about 10,000 years befpre we get to the point where we can defuse nearby supernovae before they go off, or things like that. So really, we're looking at a situation where we can put any number we like for N here that is consistent with cosmological constraints. So I'm just going to stop there and say, well, if you haven't read this book you bloody ought to have done - it came out two years ago. I will just mention one thing, which is that there's a paperback edition that came out one year ago; get that one, because it's got an extra chapter in it. The amount of progress that happened in those 12 months between the two editions was so great that we actually had to write an entire new chapter. So obviously we need your money, we need your time, you know how it is, and I'll stop there.