Life Extension Therapies
Life Extension Therapies
Aubrey de Grey (Chairman, Methuselah Foundation) gives expert video advice on: What are 'life extension therapies'?; When did life extension studies first begin?; What is 'rejuvenation therapy'? and more...
What are 'life extension therapies'?
Life extension therapies will be therapies that obviously extend life. It's important to understand that they will do so by extending healthy life. There's a famous myth from the Greek times called the myth of Tithonus which talks about someone who was granted immortality because he won the heart of a goddess
When did life extension studies first begin?
The study of life extension is actually in some ways older than the study of how aging happens in the first place. There are myths from many thousands of years ago like the Epic of Gilgamesh, and the myth of Thymus, that talk about life extension. So it's always been a goal for society. So as soon as people started to think scientifically about nature at all, and certainly about the human body, people were thinking about it in terms of the big enchilada, the ultimate goal, being to fix this damn problem of aging. If we come a little bit more recently, down to let's say a hundred years ago, then young people who were getting into studying biology carefully and looking at the way our biochemistry works for example, they prioritized the concept of life extension as a really important aspect of this. It's only really in the past fifty years as biologists have had to worry more and more about funding, and have decided to try to be as politically correct as possible, if you like, to and try not to scare the politicians, that its become a little bit less popular to do this. And most biologists in fact try not to talk about life extension as part of their work they're trying to do. I think that's been a massive mistake. I think that trying to pull the wool over politician's eyes, effectively, has not been the way to go. Politicians are far less dumb than they look.
What is 'rejuvenation therapy'?
Rejuvenation therapy is therapies that actually reverse the process of aging. In other words, not actually reverse the mechanistic process, the actual chemical reactions that occur, but structurally reverse the process of aging so that the body is restored to something like the state that it was in, in terms of its composition that it had at a younger age. Of course this only applies to adulthood. We wouldn't call a rejuvenation therapy something that restored us to childhood, but within adulthood, yes, the idea of Rejuvenation therapy is to actually repair and reverse the accumulating damage of aging.
What is your master plan for extending the human lifespan?
SENS is an acronym. S-E-N-S. It stands for Strategies for Engineered Negligible Senescence. It is my overall grand plan for seriously fixing aging. It consists of a seven point plan that is based on the categorization of aging and aging damage into seven major molecular and cellular phenomena: The loss of cells, the gain of too many cells, the accumulation of mutations in our chromosomes, the accumulation of mutations in the mitochondria, the accumulation of indigestible molecules inside the cell, the accumulation of indigestible molecules outside and especially in between the cells, and the stiffening of long lived structures made of proteins that need to be elastic in order to work. Those seven things can all, in principle, be repaired or reversed, or in a couple of cases made harmless, obviated, by technology that either already almost exists or it's at least very foreseeable that we can describe in a lot of detail. That's why I'm optimistic about the forseeablility of real anti-aging medicines, so to speak, and therefore the eventual and robust extension of healthy life spans.
What is 'tissue rejuvenation'?
We are made of tissues. And therefore, the process of rejuvenation of the human body is tissue rejuvenation. It's the repair of the structure of tissues and therefore in sum the repair of the overall body. The restoration of the structure of tissues and therefore the body to the state that it was in at a younger age. Now, tissue rejuvenation can be done in a number of ways. One way is simply by tissue replacement. So for example, the whole field of tissue engineering revolves around the idea of constructing outside the body an organ, like the liver for example that needs to be replaced, and then putting the whole liver back in replacement of the one that may have become diseased or old. And one could imagine that with most of our tissues. The one tissue for which that approach would rather defeat the object is the brain. And so, it's not a complete solution. So, tissue rejuvenation also includes the repair of organs by the replacement not of the whole organ in one go but rather of just the cells or even sub cellular components that have become damaged. So for example, stem cells therapy is an aspect of tissue rejuvenation where you put in cells that divide, differentiate and develop to replace cells that have become diseased and dying.
What are 'stem cells'?
A "stem cell' is defined as a cell which can divide in such a way that at least one of the daughter cells retains just as much ability to continue dividing as the original mother cell had. And generally, exactly one of the two cells retains that property. And the other one becomes a little bit more, what we call, differentiated and starts down a pathway of commitment to becoming a particular type of normal cell like - you know, a blood cell, or a liver cell, or whatever. And most of our tissues are made up predominately of the differentiated cells, but we have a small minority of the stem cells that are able to divide to give rise to the replacement of any cells that die. Different tissues have different numbers of stems cells. And different types of stem cells divide at different frequencies or in different circumstances. So there are many different types of stem cell. In particular, very early on in life, early in pregnancy, we have particular types of stem cell that are very versatile; very able to become lots of different other types of cell. Those are called embryonic stem cells. And we really don't have any of them in the body at the moment. We would like to be able to take cells that we do have in adult bodies and revert them to this embryonic stem cell state - and we're getting much better at that. There are now reports of being able to do that rather well. Which would be great if we could do it, because then we wouldn't need to destroy embryos in order to extract embryonic stem cells from them, and that would solve a whole bunch of ethical issues. And they are of course, very well-known in the United States. The main problem with harvesting embryonic stem cells from an adult body is that we would have to reverse a whole bunch of changes that spontaneously happen in the process of development from an embryo through to being a fetus and then a baby, and then an adult. And those processes just cause all of the embryonic stem cells to become more committed cells - stem cells that are less powerful. That's the main problem. Embryonic stem cells however, are really useful because we sometimes need cells that can be developed into all manner of different types of cell. And we just - the easiest way to get them, the most effective way to get them is by taking them from early embryo. There is a method called, "stem cell nuclear transfer," which is part of this process. And it's a trick that allows the embryonic stem cells we derived to avoid being rejected by our immune system after they have been differentiated into a different type of cell and put into the body to do some particular job.
How might stem cells increase my life span?
Stem cells as an aspect of rejuvenation therapy, are certainly going to be very important because they're required as a way to replace cells that die, and that are not naturally replaced by the division of other cells in the body. They will not be terribly important for tissues in which normal cell replacement happens perfectly naturally. For example, the liver. But in tissues like the heart, or some parts of the brain that are particularly susceptible to losing cells, or also some slightly more esoteric tissues, like the thymus. These tissues shrink with age, or in some cases they don't actually shrink physically, but they'll die, and the other cells around them just become larger, and the structure gets weaker as a result. Sometimes the tissue just fills up with fibrous material that isn't cells at all. The effect in all cases, is that the tissue the cells make up, doesn't work so well, and we have to do something about that. Stem cells are essentially precursors of the cells that these tissues are made of. And if those stem cells are introduced into these tissues, and directed in such a way as to differentiate, and develop to become the cells that are missing, then the tissue is restored to full function--that's the theory anyway.
How might organ transplants extend my life?
It may turn out that some tissues can be most effectively rejuvenated by whole cell replacement. For example the heart undergoes a number of different changes in aging. Things like; loss of cells that are compensated inadequately by normal processes, by for example the growth of the remaining cells, not divisional, but just getting larger, or the introduction of fiber use material. Also, the accumulation of mutations happens in the heart and that may make it weaker, thing like this. And we, of course, have for some decades been doing heart transplants, putting someone else's heart into the body of someone who has a diseased heart, and we're now fairly good at that. But, the problems is that we can only get the new heart to put in from somebody who's been unlucky and been killed in a car crash, or something like that. It would be much better if we had a much better supply of hearts, and the only way to do that is to be able to make them without using humans. We're getting better at this, but it's still a very long way to go before we can actually engineer a heart. A human heart in the laboratory to put into the body. But we will get there and when we do that may be a much more effective, and thorough comprehensive way to rejuvenate the heart than simply tying to replace the individual cells that were missing or trying to obviate the mutations.
What is 'gene therapy'?
Gene therapy is going to play an enormous role in rejuvenation therapy because a number of the changes that we need to make in order to stop our bodies from accumulating various types of damage involve the introduction of genes that we don't have or, in some cases the removal of genes that we do have, or in other cases actually the relocation of genes that we do have from one place to another. So, for example, the removal of indigestible molecules in the salad is going to be achieved by giving us new genes that encode enzymes that can break down things that none of our existing genes can break down. And the problem of accumulating mutations in the mitochondria is likely to be solved by making copies of the mitochondrial genes and putting them into nucleus. That is something that again will require gene therapy. Cancer is probably going to be treated by eliminating some of the genes that we already have naturally in our cells that allows cells to divide indefinitely.
What is 'calorie restriction' CR?
Calorie Restriction is limiting dietary energy in take to improve health and slow the aging process.
How safe and effective is calorie restriction?
It's very easy if you hear that kind of restriction is a good idea and might save your life to get it wrong. To essentially starve yourself of calories, but at the same time, starve yourself of micronutrient's that you need. And the most effective calorie restriction in experiments that have been done in the laboratory on rats and mice and such have be done my carefully enriching the food in various micronutrients. So, that even though the animal's are not getting so many calories, they're getting plenty of everything else. Now, of course, we can do this as humans as well, just by being very careful about the composition of our diet. And, certainly people who do calorie restriction, themselves, have a very rigid regimen of determining exactly what they're getting and what they're not getting, and making sure that they don't get short of any micronutrient's. If you do that, then I think the overwhelming evidence, is that, doing calorie restriction is indeed safe. The new doubt I have is whether it's truly effective.
What is 'cryonics'?
Cryonics is the preservation of a patient, a body that has only just died, has only just become legally dead in liquid nitrogen at very, very cold temperatures. The idea here is that at really cold temperatures the decay of the body that happens after death is arrested; it just stops happening. And therefore the body can be preserved indefinitely, certainly for thousands of years. The idea of doing so is that there is a good chance, or at least many people think there is, that in decades to come or centuries to come, we will have such good medicine that we will be able to revive these people. That because they have only gone downhill, they have only decayed a tiny bit since they died, that we will be able to warm them up again and repair the damage that happened and of course repair also the problem that killed them in the first place. I think cryonics is a realistic, reasonable concept because really it's just a natural extension of the work that I'm already doing to rejuvenate the bodies of the people whose hearts are still beating. And it's very important to remember here that death, from a legal perspective, is not a biological phenomenon. The concept of legal death is really just a convenience. It's something that we have so that we can decide whether someone's next of kin can inherit their wealth. But ultimately, what it comes down to is an arbitrary discussion of when someone is in too bad a state for it to be realistic that we can restore them to any sort of health by medical means, such as because their heart has stopped or because their brain has stopped. In actual fact, the difference between the biological state of someone who has just become legally dead as opposed to someone who is just about to become legally dead; there's no difference at all. So, if as soon as someone has become legally dead, we can arrest their decline by cooling them down very fast and freezing them, then we have a pretty good chance of preserving their natural state, including of course, the state of their brain, their personality and memories and so on in such a way that future medicine could indeed revive them and cure them.
What is a 'growth hormone'?
Cell division is a process that needs to be carefully controlled. Both during adulthood and also especially during early years, during development in the womb or during childhood. The body has developed a lot of very sophisticated ways to exercise that control. This one type of control circulates in the body, in other words, its a hormone, that is constructed by a particular part of the body and circulates around the body and affects other parts of the body. Human growth hormone is one of those. If we dont have enough human growth hormone in early life, then we end up not growing very much, and being short stature and so on. And some people are genetically deficient in human growth hormone and that can be cured or at least alleviated by injection of human growth hormone. So a number of people you have with problems, just get human growth hormone in childhood and that will allow them to grow to a normal height. However it is much less clear whether it is good for anything in terms of aging. It turns out that in the laboratory where we make mice genetically deficient in growth hormone itself or with some of the other proteins that the hormone interacts with, then they actually live longer, they're smaller but they live longer. This maybe because growing to a normal size is essentially an error-prone process. If we have hormonal deficiency that causes us to grow more slowly, then cell division and all the processes involved in cell division may happen a little bit more accurately so that less damage have accumulated as a side effect of of doing so and that may underlie the fact that such animals tend to live a bit longer. If we have normal levels of growth hormone early in life but later in life we add some more, then that may have some benefits that certainly does help, in some people, to alleviate and even reverse the loss of muscle mass that happens during elderly life. On the other hand, it may be that having too much growth hormone late in life may increase one's risk of cancer, because of course cancer is cell growth and division, and if we do that too much then the cancer grows more quickly, in principle. It may be that some people will be worth to take growth hormone because they are not in danger from dying anytime soon from cancer but they are suffering alot of loss of muscle mass and for some other people it may be the other way around. However I want to emphasize that there's an awful lot we don't know about this at the moment so we need more data.
How much will life extension therapies cost?
When really effective rejuvenation therapies come along-- able to actually take a middle aged person and rejuvenate them back to, let's say thirty or forty years old, and when they've aged again to sixty and to do it again, and so on-- when these therapy's come along, they are probably going to be very expensive. Just like any technology is when it first comes along. Another thing however to remember is they are going to be very risky and experimental. There probably not going to be very safe at all, because if people are going to be so desperate to get their hands on them, that sort of regulatory structure that we have now will probably not actually be applied to them. So in some terms it doesn't matter if they'll be expensive. The big reason why it doesn't matter so much, is that the pressure to improve these therapies will be enormous through society. There will be enormous amount of money being spent on refining them. And that will apply not only to the safety, but also to the cost. People will figure out ways to make them more convenient, and more comprehensive, and safer and therefore cheaper. And so I expect that it will be something that will not be appreciatively more expensive than standard care for the elderly at the moment. And of course it will ultimately be more effective, because it won't be keeping people alive in a frail state for an extra couple of years. It will be keeping people alive in a youthful state for an arbitrary amount of time.
What types of experiments are necessary to test life extension therapies?
The only way you are going to be able to figure out whether a particular therapy or combination of therapies make sense and actually works against aging is by taking an organism and trying it. Luckily we have organism that we can use in the laboratory that have much shorter lifespans than we ourselves do. Mice, for example, even pretty robust long-lived mice naturally live only for about 3 years. So it doesn't take very long to do an experiment and find out whether the therapies you have invented will actually extend the lifespan of mice. That is especially true for rejuvenation therapy, because in that case the mice are already middle-aged before you begin. So let's say you are looking at mice that normally are going to live to be 3 years old. You will take them when they are already 2 years old and you'll know within a year whether the therapies are working because most of your normal mice will be dead, and essentially if it works hardly any of your rejuvenating mice will be dead. That is not the whole story of course because mice, even though they are fairly similar to us, they are mammals and they have most the same organs and so on, they are not quite similar to us. There are big differences actually in the way they age and the way that we age. So after we got them working in mice we then have to work out what will work in other organisms and adapt those therapies somewhat so that they do work in other organisms. And there will be a great diversity of other organisms through the years at this point after the concept has been proved in mice. I imagine there will be a lot of work going on in dogs and cats and such, also of course in primates and monkeys. But I also expect that there will be highly risky but nonetheless important experimental work being done in humans even at that stage -- humans that are in the later stage of some aspect of aging at that point and don't have much to lose.