Aubrey de Grey of the SENS Research Foundation maintains an active schedule of presentations, and the interview here is one of a series of recent discussions in which he talks about timelines, funding, and progress in recent years. We're in the midst of a tipping point of sorts, as the SENS view of rejuvenation research gathers more attention and legitimacy in the eyes of the public and various sources of funding. Senolytic therapies to clear senescent cells are well into the first stages of clinical development, with new compelling data for cellular senescence to contribute to specific age-related diseases arriving every month now. Targeting senescent cells for destruction was one of the strategies that de Grey started to advocate all the way back in 2002, when the research community was much less welcoming of any discussion of the treatment of aging as a medical condition, and there was little to no funding for such approaches despite the extensive supporting evidence. It doesn't hurt to be proven right when it comes to reinforcing an agenda.
What is the future timeline for the advent of rejuvenation therapies sufficiently effective to grant a few decades of additional healthy life, and substantially rescue aged people from the immediate consequences of high levels of cell and tissue damage? In one sense we can put together a decently robust timeline for SENS research and development and estimate ten years to get to robust mouse rejuvenation in the laboratory, followed by a further ten years to push the first implementations into the clinic. We can feel fairly good about that, and indeed that planning has been carried out at the Methuselah Foundation and later the SENS Research Foundation several times over the past fifteen years. But that best possible pace of progress is entirely dependent on sufficient funding, $100 million or more each year, as well as the rapid cooperation of regulatory bodies. Both of these are sticky, complicated persuasion and human interaction problems. Thus no-one can predict how long it will take to (a) bootstrap SENS rejuvenation research to the necessary funding levels and (b) solve or work around the roadblock to the treatment of aging set up by the FDA and other regulatory bodies sufficiently well to allow rapid clinical implementation of therapies.
We should be optimistic, however, given that this does boil down to persuasion and funding as the limiting factors. That the science is a relatively clear road, and that the delay is all a matter of gathering sufficient support, means that everyone and anyone can help to accelerate progress towards the medical control of aging, and an end to age-related disease. It doesn't require years of schooling to support a field of medical research as a patient advocate or a fundraiser or an entrepreneur. When interested scientists with promising plans are limited entirely by a lack of funding, we can all step up to make a difference. That has happened already: it is possible to look back at the fifteen year history of SENS advocacy and research, and track its progress from an idea with zero funding to the existence of several non-profit foundations devoting millions of dollars in philathropic funding every year to the challenge. Our community achieved a great deal over the course of the early, challenging years, and that success can and will continue, with it becoming ever easier to raise ever more funding for research and development.
Your foundation is working on an initiative requiring $50 million in funding-
Well, if we had $50 million per year in funding, we could go about three times faster than we are on $5 million per year.
And you're looking at a 2021 timeframe to start human trials?
That's approximate. Remember, because we accumulate in the body so many different types of damage, that means we have many different types of therapy to repair that damage. And of course, each of those types has to be developed independently. It's very much a divide and conquer therapy. The therapies interact with each other to some extent; the repair of one type of damage may slow down the creation of another type of damage, but still that's how it's going to be. And some of these therapies are much easier to implement than others. The easier components of what we need to do are already in clinical trials - stem cell therapies especially, and immunotherapy against amyloid in the brain, for example. Even in phase III clinical trials in some cases. So when I talk about a timeframe like 2021, or early 20s shall we say, I'm really talking about the most difficult components.
What recent strides are you most excited about?
Looking back over the past couple of years, I'm particularly proud of the successes we've had in the very most difficult areas. If you go through the seven components of SENS, there are two that have absolutely been stuck in a rut and have gotten nowhere for 15 to 20 years, and we basically fixed that in both cases. We published two years ago in Science magazine that essentially showed a way forward against the stiffening of the extracellular matrix, which is responsible for things like wrinkles and hypertension. And then a year ago, we published a real breakthrough paper with regard to placing copies of the mitochondria DNA in the nuclear DNA modified in such a way that they still work, which is an idea that had been around for 30 years; everyone had given up on it, some a long time ago, and we basically revived it.
What do you think are the biggest barriers to defeating aging today: the technological challenges, the regulatory framework, the cost, or the cultural attitude of the "pro-aging" trance?
One can't really address those independently of each other. The technological side is one thing; it's hard, but we know where we're going, we've got a plan. The other ones are very intertwined with each other. A lot of people are inclined to say, the regulatory hurdle will be completely insurmountable, plus people don't recognize aging as a disease, so it's going to be a complete nonstarter. I think that's nonsense. And the reason is because the cultural attitudes toward all of this are going to be completely turned upside down before we have to worry about the regulatory hurdles. In other words, they're going to be turned upside down by sufficiently promising results in the lab, in mice. Once we get to be able to rejuvenate actually old mice really well so they live substantially longer than they otherwise would have done, in a healthy state, everyone's going to know about it and everyone's going to demand - it's not going to be possible to get re-elected unless you have a manifesto commitment to turn the FDA completely upside down and make sure this happens without any kind of regulatory obstacle.
I've been struggling away all these years trying to bring little bits of money in the door, and the reason I have is because of the skepticism as to regards whether this could actually work, combined with the pro-aging trance, which is a product of the skepticism - people not wanting to get their hopes up, so finding excuses about aging being a blessing in disguise, so they don't have to think about it. All of that will literally disintegrate pretty much overnight when we have the right kind of sufficiently impressive progress in the lab. Therefore, the availability of money will also open up. It's already cracking: we're already seeing the beginnings of the actual rejuvenation biotechnology industry that I've been talking about with a twinkle in my eye for some years.
I'm sure you hate getting the timeline question, but if we're five years away from this breakthrough in mice, it's hard to resist asking - how far is that in terms of a human cure?
When I give any kind of timeframes, the only real care I have to take is to emphasize the variance. In this case I think we have got a 50-50 chance of getting to that tipping point in mice within five years from now, certainly it could be 10 or 15 years if we get unlucky. Similarly, for humans, a 50-50 chance would be twenty years at this point, and there's a 10 percent chance that we won't get there for a hundred years.
You famously said ten years ago that you think the first person to live to 1000 is already alive. Do you think that's still the case?
Definitely, yeah. I can't see how it could not be. Again, it's a probabilistic thing. I said there's at least a 10 percent chance that we won't get to what I call Longevity Escape Velocity for 100 years and if that's true, then the statement about 1000 years being alive already is not going to be the case. But for sure, I believe that the beneficiaries of what we may as well call SENS 1.0, the point where we get to Longevity Escape Velocity, those people are exceptionally unlikely ever to suffer from any kind of ill health correlated with their age. Because we will never fall below Longevity Escape Velocity once we attain it.
Could someone who was just born today expect-
I would say people in middle age now have a fair chance. Remember - a 50/50 chance of getting to Longevity Escape Velocity within 20 years, and when you get there, you don't just stay at biologically 70 or 80, you are rejuvenated back to biologically 30 or 40 and you stay there, so your risk of death each year is not related to how long ago you were born, it's the same as a young adult. Today, that's less than 1 in 1000 per year, and that number is going to go down as we get self-driving cars and all that, so actually 1000 is a very conservative number.