Reversing The Aging Process

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Reversing The Aging Process

Aubrey de Grey (Chairman, Methuselah Foundation) gives expert video advice on: Can the aging process be slowed down or reversed?; Why are mice being used to study rejuvenation technologies?; What is 'Robust Mouse Rejuvenation' RMR? and more...

Can the aging process be slowed down or reversed?

It's going to be very hard to slow down the aging process and it's going to be rather easier to reverse it, it turns out. This is because, just like a simple machine like a car or a house or even a nuclear power station, which is complicated by manmade standards, but still simpler than the human body, it's easier to repair ongoing damage than to prevent the damage from happening. Classic cars, for example, are a hundred years old by definition and yet they weren't built that way. They were built only to last ten or fifteen years and the reason they have lasted longer is because the people who own them do a large amount of repair and maintenance on them. They don't stop the damage from happening; rust still happens to classic cars, but the owners of the cars get rid of the rust. That's the way that we are going to figure out how to maintain the human body in a healthy and vigorous state.

Why are mice being used to study rejuvenation technologies?

Mice are a really useful experimental organism for many areas of biology and especially for their work that I'm doing on combating aging. There are really three main reasons why they're so useful. First of all they've been used in biology for many, many decades and so we've developed a great many techniques for manipulating mice. Putting new genes into their bodies for example so that we can identify what happens to them and these techniques have been developed for reasons that have nothing to do with life extension but they work just as well for the sort of things that we need to do the experiments that we need to do. The second thing that's really good about mice is that they're not very expensive they're more expensive than fruit flies but they're not very expensive so we can do an experiment on a lot of mice at the same time and see what happens. The third reason of course is that they don't live very long so we're able to find out pretty quickly whether these mice are actually going to be living longer as a result of the therapy than if they didn't have the therapies. Now all these things are true to an even greater extent for fruit flies for example, fruit flies live a really short lifespan and they're even cheaper than mice and they've also been worked on in the laboratory for just as long as mice. But unfortunately they're bodies are built very differently from our bodies and so if something works in fruit flies that's only very weak evidence that it will really work in humans whereas if it works in mice that's much stronger evidence.

What is 'Robust Mouse Rejuvenation' RMR?

In order to determine whether we have made enough progress in developing these therapies for mice, we need some sort of milestone that says, OK, this is good enough to be, what we call, a real proof of concept. That if we could do this in humans, it would really work. And the milestone that I've defined that I think is an appropriate one, I call Robust Mouse Rejuvenation. What it involves is, first of all, it involves treating mice that have nothing inherently wrong with them. A lot of mouse strains don't live very long anyway. They live maybe only a year and a half or two years because there are congenital problems that they have. And if you make those sorts of mice live a bit longer, then you haven't really shown anything for sure. You may have only fixed the particular problem that they had. Whereas if you take the strain of mice that are already unusually long-lived, let's say they live already three years. Then you've really got no chance of increasing their lifespan except by something that really properly combats their aging. So Robust Mouse Rejuvenation is defined as taking both mice and increasing their life span. But there's more: first of all, we have to say how much you need to increase their lifespan. And I say that for this mouse, what we need to do is to increase their lifespan by two more years, so that they live for an average of five years. Finally, there's third criterion incorporated in the definition of Robust Mouse Rejuvenation, which is that the mice should not have any treatment at all until they're already two years old, with one year to live unless they get any treatment.

Will people eventually stop dying from old age?

We will always have the possibility of dying from old age, even when the therapies exist. Just as today, we always have the possibility of dying of polio or tuberculosis. But we will not have the necessity to die of old age because these therapies will be able to postpone the accumulating molecular and cellular damage of aging indefinitely, just in the same way that classic cars do not actually die at all. They don't have a mortality rate. The only time a classic car dies is when its owners stop looking after it.

Will eternal youth be a reality 50 years from now?

It's unclear whether we will completely have brought aging under control in 50 years. But I think that if we get good funding, especially from the early work that needs to be done on mice in the next 10 years, then there's a very good chance that we will be there. And if we can describe that as eternal youth, I suppose the only problem is with the word "eternal", because it sort of implies that we won't even be hit by trucks and so on. But certainly we will be able, once we reach that point, to be able to fend off the decline in health and vigour and vitality that currently accompanies aging.

Will life extension therapies be able to reverse the effects of Alzheimers and Parkinsons?

The brain is, in many ways, the most important tissue to rejuvenate because having a youthful body with an aged and decrepit and demented brain is not really a particularly attractive prospect. But luckily the therapies that we need to apply to the brain are more or less the same as therapies that we need to apply to the rest of the body. Because, after all the brain is made out of the same sort of stuff, it's made out of cells mainly. And the cells are more or less structured in the same way, that is, of course with some differences. So, for example Alzheimer's disease is characterized by the accumulation of junk inside the cells and the accumulation of junk outside the cells and the loss of cells that are not naturally replaced. And all of those three things happen also in other tissues and we have particular proteins and we have particular approaches within the program to actually repair all those types of damage.

Will life extension therapies be able to reverse the effects of HIV and AIDS?

Infectious diseases are a whole different challenge from the challenges of aging. Though there is actually some overlap, certainly some infectious diseases accelerate some aspects of aging. But, the treatment of infectious diseases is something that will continue to be an active research area long after aging has been completely brought under control. Simply because new infectious diseases are constantly evolving out in the world, and becoming important. I think that one of the greatest tragedies of contemporary medicine is that not enough work is done to develop good vaccines for diseases that especially afflict the developing world. And the reason that not enough work is done is straightforward with economics, vaccines aren't very profitable. But when aging has become a thing of the past, it's going to be a very different situation. Infectious diseases will be one of the major risks for death, and therefore, will be much more prioritized in terms of more of a biomedical research effort. So if we take HIV as a straightforward example, the big problem with HIV is that, when you get it, the body doesn't know how to get rid of it. We haven't got good vaccines, good things to actually cure HIV. But, there are new ideas, and new approaches being developed all the time, that will actually remove HIV from the body. And eventually, that will be developed, and the affect that HIV and other similar infectious diseases have on the aging process will of course, thereby, also be removed.

How will life extension therapies affect diseases like cancer?

Cancer is very much a part of aging. Anyone who tells you cancer is a disease and it's not part of aging, they don't know what they're talking about. Some cancers, of course, are not part of aging. Some cancers are early onset childhood diseases, for example. But most cancers are age related. They're age related because they are the late stage consequences of various aspects of the ongoing accumulation of damage, especially the ongoing accumulation of damage to our chromosomes. But mutations, and another type of damage called ethamutations, which is, essentially, not changes to the DNA sequence, but changes to the way that sequence is translated into protein. And, we definitely need to fix that. If we only fix all the other aspects of aging, and we didn't do much about cancer, then our lifespans would only be increased by maybe fifteen, twenty years on average. And we'd all die horribly instead of only twenty percent of us or whatever dying of cancer. So, one of the strands of the Sands program is specifically targeted at cancer, and it's extremely complex and elaborate, but I think necessarily ambitious approach to really defeating cancer. They really take cancer as seriously as it needs to be taken. Because in a way, cancer is the most difficult aspect of aging to fix. Because cancer is a disease of mutation, it has natural selection at its disposal. There are a trillion cells in a big cancer, and they're all dividing away, trying figure out new ways to divide even more effectively and evade our therapy.