Fight Aging!

Here is the transcript of an interview, published last week, with Aubrey de Grey, advocate and coordinator of rejuvenation research, originator of the Strategies for Negligible Senescence (SENS) scientific programs, and cofounder of the Methuselah Foundation and SENS Research Foundation. Over the past fifteen years, de Grey and his growing network of allies within and outside the scientific community have had an outsized influence on the culture of aging research, on public perception of the treatment of aging as a medical condition, and on meaningful progress towards therapies capable of rejuvenation. All of this has been achieved the old-fashioned way, ignored by mainstream funding institutions, and proceeding on the basis of a great deal of hard work and the pledges and philanthropic donations provided by a small, enthusiastic, and visionary community of supporters.

At the turn of the century, the field of gerontology was run by senior researchers who actively suppressed public discussion and funding aimed at lengthening life or addressing the causes of aging. That was the product of decades of setting themselves up in opposition to the fraudulent "anti-aging" marketplace of pills and potions, but it was still the wrong thing to do - and it held back progress. At that time, despite the wealth of evidence to point the way to the molecular damage that causes aging, anyone talking seriously about treating aging was mocked. That was the environment facing the first members of the modern rejuvenation research community of patient advocates and a few brave researchers willing to risk their careers.

In the years since then, we have collectively brought about a sea change, a great transformation in both research community and culture. Now, members of the scientific community enthusiastically discuss the treatment of aging, how to intervene in its progression, without fear of repercussion. A hundred times or more the investment in viable rejuvenation research programs is taking place, and venture investment in companies working on ways to address the medical condition of aging is well underway. The first rejuvenation therapies, those based on clearance of senescent cells, are under development in startup biotech companies, on their way to the clinic. None of this would have happened anywhere near as rapidly without the actions of those first individuals brave enough to champion an unpopular cause, to provide the first philanthropic funding for advocacy and research, to step up and make a difference, to swim against the current of the times.

Ending Aging, with Aubrey de Grey

Mark Sackler: You wrote the book Ending Aging in 2008. You identified seven areas of cellular and intracellular damage that you think need to be reversed as the best process for reversing aging. In the nine years since you wrote that book, what has changed? Are we where you thought we'd be by now? Have there been any breakthroughs?

Aubrey de Grey: People often ask me, "When are you going to write a new book - when are you going to update Ending Aging?" It's not a priority right now. It could easily be presumed to be saying that it's not my priority simply because I haven't made much progress and there's not much to say. But it's just the opposite of that - there's been massive progress, but it's been pretty much exactly the progress that we were predicting in the book. So essentially the plan is the same 7 points. There's no problem number 8 or 9 that came along and had to be added. And furthermore, the solutions that we discussed in the book are still the same solutions. There's nothing that has come along that has made us have to revisit it and say, well, OK, the approach that we thought was going to be the right way to go is actually much harder than we had expected and therefore we need something else­­ - none of that has happened. There have been some surprises, but they have all been good surprises in the form of innovative technologies­ - new discoveries that have allowed us to pursue the same approaches but more effectively and more rapidly than we otherwise thought.

Now there is one downside, though, which is, back then I started making predictions about the time frames of how long this will all take. And of course, I was always making a lot of caveats emphasizing that a prediction of time frames was very speculative for any pioneer in technology. However, the fact is we haven't hit the time frames I was saying that we would. But what's gone wrong is not the science, but something else. The answer is the money. The fact is that my predictions were always very strongly conditional on the ability to bring in funding that was sufficient so that the rate of progress would only be limited by the sheer difficulty of the technology, the actual science and practice. I believe we've been going along three times more slowly than that initial prediction simply because it's been so much more difficult than I had expected to attract sufficient funding.

Mark Sackler: What about using pharmaceuticals or supplements to slow the aging process - to buy more time before we reach SENS 1.0? There are several agents out there now. Metformin is about to go into human clinical trials, Rapamycin is in trials with dogs, and NAD+ supplements are all the rage right now. What's your take on all of this?

Aubrey de Grey: So I'm all for this work. I think that it's very valuable in helping people to stay healthy longer. However, there is a very important feature of all of these supplements which is very often swept under the carpet by the researchers and companies that are working on them. They're all hypothesized to work by calorie restriction memetics. In other words, drugs that trick the body into thinking it's not getting as many calories as it would like, even though it is getting them. So that's wonderful. Except that there's a huge catch, and it has been a totally incontrovertible message in the animal data for decades. It is a fairly scandalous thing that has been swept under the carpet. The problem is that different species respond by different degrees to this kind of restriction. Specifically, long-lived species respond less than a short-lived species. The world record for how much you can extend the life of a nematode worm that normally lives about three weeks is by a factor of five. But then if you go up and look at organisms that live a couple of years, like mice, you can only get a factor of one and a half. That's still very impressive but it's definitely not five. But unfortunately, this trend persists as you go higher up the chain.

For example, about 20 years ago you're in a very thorough and rigorous trial made with Labrador dogs, which normally live about 11 years, and on the whole, it resulted in only about a 10% increase in lifespan. And over the past 20 odd years, two groups in the US have performed extraordinarily expensive and time-consuming experiments of calorie restriction on monkeys, and depending on how you interpret that, it yielded maybe a couple of percent increase. So, the prognosis for humans is not terribly good. Now again I want to emphasize I'm fine with the fact that people are excited by these drugs, because they do seem to keep people healthy; they are protective, but it is critical not to make the extrapolation that they are the foundation to extending life - because in no way has that happened.

Mark Sackler: One of the hottest biotech topics lately has been genetic editing, and there have been at least two individuals who recently had genetic editing therapy performed on themselves. I wonder what you make of those efforts.

Aubrey de Grey: Well, first let me talk about gene targeting in general. CRISPR is a fantastic breakthrough. When I was talking at the beginning about the surprises that we'd had, that's probably the single biggest one - because the fact is that before it came along, there was very little that we could do to change genes. We had methods for gene targeting, for modifying the genome, but they were very laborious and expensive. Now as for self-experimentation one can look at it in a whole bunch of ways. First, one can be curmudgeonly about it and say, well okay, this is very unsafe. God knows what's going to happen if bad things happen if these people die as a result of that therapy; it is going to set back the whole field to a large degree. That's all true up to a point. But at the same time, we have to remember that self-experimentation is not new. It has a long and very distinguished history in biology. JBS Haldane, the distinguished and respected British biologist from the 1930s, was rather famous for doing things to himself that I certainly wouldn't dare to. Certainly, the scientific information that will come from this sort of experimentation effort is probably very limited, simply by the fact that it is a sample size of 1. But on the other hand, the high-profile news that arises and the fact that people are talking about what is happening and a discussion is actually occurring, has its own value. If people are not interested in something, it's very hard to get them to think about it, whereas if they are interested, even for an unusual and rather tangential reason, you can educate them.

Mark Sackler: Earlier this year I interviewed David Wood on his book The Abolition of Aging. In it he forecast that by 2040 there is a 50-50 chance of there being widely available affordable rejuvenation therapy. How do you feel about that forecast right now? Is it overly optimistic? Is it well within reach if there's enough money, or is it totally uncertain?

Aubrey de Grey: It's pretty much exactly the same as my prediction. That may not be a coincidence.