Fight Aging!

Here I'll point out a twenty minute podcast interview with Aubrey de Grey of the SENS Research Foundation and Brian Kennedy of the Buck Institute for Research on Aging. This was recorded at the recent Rejuvenation Biotechnology 2015 conference, hosted by the SENS Research Foundation in the Bay Area, where both institutions are based. The SENS Research Foundation remains perhaps the world's only organization focused wholly on developing the fundamental biotechnologies needed for near future rejuvenation therapies capable of actually reversing the course of aging. A little of the work taking place at the Buck Institute is funded in part by the SENS Research Foundation, such as the research programs in the Campisi Lab aiming at the end goal of senescent cell clearance therapies, but for the most part the Buck Institute funds much more modest and mainstream goals in aging research, meaning attempts to slightly slow the aging process through traditional approaches of investigating cellular metabolism and drug discovery.

Brian Kennedy and Aubrey de Grey on their Converging Approaches to Aging Research

Last week we attended the 2015 Rejuvenation Biotechnology Conference where we heard about the latest developments in aging research. We were fortunate enough to sit down with two of the major figures in the field of aging research, Aubrey de Grey, CSO of the SENS Research Foundation and Brian Kennedy, CEO of the Buck Institute for Research on Aging. Brian and Aubrey gone about their work in different ways but say that their approaches are now converging as the momentum behind aging research increases. How do the two see the field since Calico and Human Longevity emerged? What developments in the past year stand out to them? Join us for an exclusive interview with two of the aging field's visionary leaders.

I put in a fair attempt to extract coherent text from the audio via software, but it wasn't on the cards today, or at least not via the standard recourse of feeding it to CMU Sphinx. If anyone else has better luck, let me know. In the meanwhile, here is a transcription of the middle of the interview, which might be of more interest to those of you who have followed the evolution of SENS since the early days.

Moderator: Let's try to hone in on the difference between you two and your view of aging, and what should be done. I mean, you know each other, so maybe you could just speak up.

AdG: Ok, well, so the big thing, the big innovation that I introduced fifteen years ago was the idea that we might actually find it easier in the long run to postpone substantially the ill-health of old age in human beings by not slowing down the rate at which the body creates damage to itself as a side-effect of normal metabolic processes, but rather by periodically repairing that damage after it has been created - but of course before it gets to a level that is so bad for us that we start going downhill.

Moderator: Ok, so one focused on repair...

Aubrey: That's right, that was the idea I brought forward. And the basis for that idea came, in large part, from areas of biology that had never previously been associated with the biology of aging. So that meant of course that the people who were working in the biology of aging were completely unfamiliar with those areas. It took a long time for me to actually make that case, and only because I had to bring together a lot of scientists who had never talked to one another before, and generally get people to pay attention to areas of biology that they had previously thought were not relevant to their work.

Brian: I think there has been some convergence on our end from the point of view that we've been following the genetics of aging, and have identified a lot of genes that impact the aging process. It seems clear that while some of them may prevent the onset of damage, a lot of them can actually induce repair mechanisms to clean up the damage that exists. So I think that at least superficially there was a significant difference in what we were saying ten years ago - and in reality there was some difference too - but there has been a lot of convergence on both sides so that I doubt that our messages are all that much different now.

Aubrey: Right, I think that a lot of the differences were more perceived and not so real, and I think the mutual education that has gone on in the meantime has clarified that, and besides there isn't all that much difference in terms of the emphasis that goes on. But I think it is also very important to note that one thing where convergence has been extremely strong is not so much on the science, but on the communication of the science. I think that now that everybody in the field is comfortable with saying that aging is really actually quite bad for you and we ought to try and do something about it...

Moderator: And that it's modifiable.

Brian: Yes.

Aubrey: Yes, and that we can do something about it, that's right. Now we all really speaking from the same hymn sheet, even that actual sort of words we're using here are converging. Brian gave an example today, in that he's talking of longevity as a side-effect of good health, and that's exactly the same thing that I've been saying.

Moderator: There is a big difference in the accents. Now how did you two meet?

Brian: It was certainly at the aging meetings, and we met at one of them.

Aubrey: The biogerontology community is actually pretty small, even now, and it was smaller ten years, twenty years ago.

Moderator: So you met ten years ago?

Aubrey de Grey: At least fifteen, I would say.

Brian: Yes, probably right.

Moderator: So was that like, wow somebody else gets it, or?

Brian: I think that there was a period where we had to get comfortable with each other. Speaking my side from the field as a whole, I think that Aubrey's message was... there was a lot of insight, and also it was also more aggressive than we were used to, so at the time we had to figure out how to deal with each other.

Moderator: Did that make you kind of bolster up, get some more courage?

Brian: It created different responses in different people in the field, but what I think is that we need multiple voices - there's no reason that the field should be speaking with only one voice. When you have different ideas and you have some people that are more grounded in saying "this is what the data has already shown" and other people that are more visionary I think it is good.

Aubrey: All that is certainly true, I agree with all of that. I think one thing that made it difficult for me to find common ground, common rhetorical ground especially, with the community back then, was something that I have been calling longevity sticker shock. Specifically that if I'm right about the science, that actually the most promising approach to postponing the ill health of old age consists of periodic preventative repair, repairing damage rather than slowing down the creation of damage, then what that implies for longevity is rather dramatically different. Slowing down the accumulation of damage, you'll get a modest increase in longevity, and that increase will be less if you start later. But if you are repairing damage every so often then you are buying time much more effectively. I pointed out way back in 2003 or 2004 that this led to a concept I call longevity escape velocity, that via really very imperfect but improving treatments one might be able to stay indefinitely ahead of the process of aging by keeping damage below pathogenic levels. This of course implies that the longevity consequences would be very dramatic. I, perhaps slightly naively, pointed this out and said, look, it's perfectly reasonable to think that there are people alive today who will live to a thousand, because that's how long you would live if you just didn't have an increased risk of death per year as we do today. And a lot people ran away very rapidly, shall we say.

Brian: Yes, it was the number. I think that at the time, that message appealed to a very small segment of the population, of which there were prominent people who were good to appeal to, but the public didn't understand enough to get to the point of your message, I think.

Aubrey: That's right, yes.

Moderator: And that's changed?

Brian: I think, well, I still don't go around talking about escape velocity. I think it is an interesting concept, but I represent a very large institute conducting NIH-funded research, and what I saying is that I don't know what is possible in the future, but I know what is possible in the short term. If we can start extending healthspan using strategies that we are developing today, the benefits of that are huge. The long-term consequences we just don't know; it could be that you're right, but I want to get those first incremental steps so that we can really get everyone excited about the approach.

Aubrey: You touched on a really important point at the beginning of that answer, which was the funding sources. When I started talking in those terms, I started getting the attention of people who wouldn't dream of funding someone like Brian because Brian's too...he's not aiming high enough, in their view. People like Peter Thiel, for example, they just want to live forever and that's that. So when I come along and I explain longevity escape velocity, they'll say "that sounds like what I want to deal with," whereas conversely, as Brian points out, if he starts talking like that in grant applications to the NIH, it isn't going to be good for his chances.

Moderator: What response have both of you had to the entrance of Calico, the Google company, and Human Longevity, Craig Venter's new company?

Aubrey: It's a complicated question. I'll talk about Human Longevity first. In my opinion they are not really working on what we're working on. They are working on personalized medicine, trying to optimize therapies that essentially already exist using analysis of large amounts of genetic data.

Moderator: So a similar company to other companies that are out there, with a fancier name?

Aubrey: I would say that definitely their hearts are in the right place, but they are a regular, perfectly normal company. They want to make profits fairly soon. Calico have set themselves up as a completely unusual company with the goal of doing something very long-term, however long it takes, they want to actually fix aging. They said so - Larry Page was perfectly clear about that. The question is how are they going about it, and that's getting really interesting. The first thing that they've done, which I feel is an absolutely spectacularly good move, is to bifurcate their work into a relatively short-term track and a long-term track. The short term track involves drug discovery for age-related diseases, doing deals with big companies like Abbvie, and so on. That's all very wonderful and all very lucrative in the relatively short term, and has more or less nothing to do with the mission for which Calico was set up - but it is a fabulous way to insulate the stuff that they do that is to do with why Calico was set up from shareholder pressure. It gets a little more complicated though. So then on the long term side, the stuff being led by David Botstein and Cynthia Kenyon, the question is how are they going about their mission. Of course an awful lot of this unknown because they are a secretive company, but from the perspective of whom they are hiring, and what kinds of work those people have done in the past, one can certainly say that they are not just focusing on one approach. They are interested in diversity. My only real concern is that they may be emphasizing a curiosity-driven long term exploratory approach to an unnecessary degree. I'm all for finding out more and more about aging, but I'm also all for using what we've already found out to the best of our ability to try stuff and see what we can do. I should emphasize that this is only my impression from a very limited amount of information available, but my impression is that it is perhaps turning into an excessively curiosity-driven, excessively basic science, inadequately translational outfit. And that's kind of what I feared when Botstein came along in the first place, because he's on record as saying he doesn't have a translational bone in his body. Now Brian could obviously say a lot more if he wants to, as he's done a deal with Calico.

Brian: Let me start by saying that I think its great that these big companies are getting into the game. Almost no matter what happens that is going to help the field get more people, more private sector people involved, maybe get Big Pharma involved, and so I think it is a good thing. I can't say too much about Calico because we have a relationship with them, but I will say that I think it is an interesting challenge when all of a sudden a lot of money is on the table, and very good people are hired to say "go solve this problem," and they haven't been thinking about that problem until a month ago. So I think what we're going to see with Calico is that they're going to continue to evolve as they go forward, and I think it will be very interesting to see the kinds of stuff they choose to do, and it may be very different two years or three years from now.

Moderator: You were saying in the panel we were just at that you thought it was a game-changer.

Brian: I think it adds great momentum, and I think it will be equally important to really get Big Pharma to get into this game too. It is easy to say you've got a ton of money, but what is a ton of money? If you're going to start doing real clinical trials, phase III clinical trials, it takes more than a ton of money; Big Pharma has to come in. Getting Abbvie involved is a good step, but it would also be good if everyone else starts saying this is the place to be.