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Follow the Example of Aubrey de Grey: In the Matter of Aging, Aim High

When it comes to evading the consequences of aging - frailty, pain, and death - our ancestors could aim as high as they liked, and it would have made no difference. The knowledge and technology of their eras could do little but somewhat slow aging, or somewhat reduce the suffering inherent in the last years of life. So, aside from the few in each generation who overestimated the bounds of the possible or deluded themselves in worse ways, they stopped aiming high. The state of the art in the human approach to aging came to be a collection of ways to avoid despair, to accept what is rather than attempt to change it, some of which are very useful indeed within that narrow scope. Stoicism, for example, is an outstanding example of thought applied to thought, an illustration of one of the ways in which philosophy can have practical outcomes, if approached in the right way.

The past is the past, however. The age in which nothing could be done about aging is over. The visionary few are now right, and the stoic many are now wrong. Rejuvenation therapies based on repair of the root causes of aging are on the horizon, and the first of them are presently in clinical development. Stocism in the face of the inevitable, for so long the rational approach to aging, is now irrational. All of the mental apparatus assembled to deal with the certainty of decline is obsolete and harmful. Coming to terms with aging is self-sabotage, a slow form of suicide on the eve of working rejuvenation treatments. Aiming high, aiming to bring aging under medical control, is the right course of action for our era. It is the way to save the most lives, to prevent the most suffering, to bring the greatest benefit to the most people.

Scientists are waging a war against human aging. But what happens next?

We all grow old. We all die. For Aubrey de Grey, a biogerontologist and chief science officer of the SENS Research Foundation, accepting these truths is, well, not good enough. He decided in his late twenties (he's currently 54) that he "wanted to make a difference to humanity" and that battling age was the best way to do it. His life's work is now a struggle against physics and biology, the twin collaborators in bodily decay. He calls it a "war on age." de Grey considers aging an engineering problem. The human body is a machine, he told me in the following interview, and like any machine, it can be maintained for as long as we want. This is not an isolated view. There is a broader anti-aging movement afoot, which seems to be growing every day.

de Grey's work is particularly interesting. For too long, he argues, scientists have been looking for solutions in all the wrong places. There is no monocausal explanation for aging. We age because the many physical systems that make up our body begin to fail at the same time and in mutually detrimental ways. So he's developed what he calls a "divide-and-conquer strategy," isolating the seven known causes of aging and tackling them individually. Whether it's cell loss or corrosive mitochondrial mutations, de Grey believes each problem is essentially mechanical, and can therefore be solved.

Sean Illing: Is there a simple way to describe theoretically what the anti-aging therapies you're working on will look like - what they'll do to or for the body?

Aubrey de Grey: Oh, much more than theoretically. The only reason why this whole approach has legs is because 15 or 17 or so years ago, I was actually able to go out and enumerate and classify the types of damage. We've been studying it for a long time, so when I started out in this field in the mid-'90s so I could learn about things, I was gratified to see that actually aging was pretty well understood. Scientists love to say that aging is not well understood because the purpose of scientists is to find things, out so they have to constantly tell people that nothing is understood, but it's actually bullshit. The fact is, aging is pretty well understood, and the best of it is that not only can we enumerate the various types of damage the body does to itself throughout our lives, we can also categorize them, classify them into a variable number of categories. We know how people age; we understand the mechanics of it. More importantly, for each category there is a generic approach to fixing it, to actually performing the maintenance approach that I'm describing, repairing the damage.

Sean Illing: Can you give me an example of one of these categories and what the approach to fixing it looks like?

Aubrey de Grey: One example is cell loss. Cell loss simply means cells dying and not being automatically replaced by the division of other cells, so that happens progressively in a few tissues in the body and it definitely drives certain aspects of aging. Let's take Parkinson's disease. That's driven by the progressive loss of a particular type of neuron, the dopaminergic neuron, in a particular part of the brain. And what's the generic fix for cell loss? Obviously it's stem cell therapy. That's what we do. We preprogram cells in the laboratory into a state where you can inject them into the body and they will divide and differentiate to replace themselves that the body is not replacing on its own. And stem cell therapy for Parkinson's disease is looking very promising right now.

Sean Illing: Is it best to think of aging as a kind of engineering problem that can be reversed or stalled? You're not trying to solve the problem of death or even aging, really. It's more about undoing the damage associated with aging.

Aubrey de Grey: Absolutely. It's a part of technology. The whole of medicine is a branch of technology. It's a way of manipulating what would otherwise happen, so this is just one part of medicine. Certainly the goal is to undo the damage that accumulates during life, and whether you call that "solving aging" is up to you.

Sean Illing: What do you say to those who see this as a quixotic quest for immortality, just the latest example of humanity trying to transcend its condition?

Aubrey de Grey: Sympathy, mainly. I understand it takes a certain amount of guts to aim high, to actually try to do things that nobody can do, that nobody's done before. Especially things that people have been trying to do for a long time. I understand most people don't have that kind of courage, and I don't hate them for that. I pity them. Of course, the problem is that they do get in my way, because I need to bring money in the door and actually get all this done. Luckily, there are some people out there who do have courage and money, and so we're making progress.

Sean Illing: Are there any ethical questions or reservations that give you pause at all?

Aubrey de Grey: Not at all. Once one comes to the realization that this is just medicine, then one can address the entire universe of potential so-called ethical objections in one go. Are you in favor of medicine or not? In order to have any so-called ethical objection to the work we do, the position that one has to take is the position that medicine for the elderly is only a good thing so long as it doesn't work very well, and that's a position no one wants to take.

Sean Illing: When will the therapies you're developing be ready for human experimentation?

Aubrey de Grey: That will happen incrementally over the next 20 years. Each component of the SENS panel will have standalone value in addressing one or another disease of old age, and some of them are already in clinical trials. Some of them are a lot harder, and the full benefit will only be seen when we can combine them all, which is a long way out.

The future of rejuvenation is only as certain as the work directed to bring it about. Once any particular technology reaches a critical mass of support within the research and development communities, then it becomes an avalanche, as is happening today for senescent cell clearance in the form of varied senolytic therapies as a method of rejuvenation. But pushing the most promising technologies to that point requires a great deal of advocacy, funding, and effort - all too many lines of research that are just as promising as senolytics still languish in comparative obscurity. Aubrey de Grey, the Methuselah Foundation, and SENS Research Foundation advocated senescent cell clearance for more than 15 years, but only in the past few years has this finally gone somewhere. It is a tough business to be in, changing the minds of the world, but the advocates were right: right to aim high, and right about the fundamental reasons for picking senescent cell clearance as an approach, based on a guiding philosophy of repair of cell and tissue damage. The mainstream research community that rejected senolytic approaches until recently was wrong: wrong to aim at the lesser target of modestly slowing aging, and wrong for choosing the guiding philosophy of altering metabolism in order to slow down the rate at which cell and tissue damage accumulates.

Research at the cutting edge depends absolutely upon philanthropy. Within the present very conservative establishment of research funding, truly novel projects simply don't get funded: there is only funding for later stages of development, once risks have been reduced and consensus exists across large portions of the research community. Prior to that, in the small and vital space where new ideas and new science happen, there is next to no support. This is why it is hard for individual career researchers to break through and aim high. But where the research community and its supporters do not aim high, they fail to achieve results such as the current brace of senolytic therapies under development, an approach with a demonstrated ability to reverse measures of aging in laboratory animals. If you look at the SENS Research Foundation portfolio of rejuvenation research, a portfolio that has long included clearance of senescent cells, the majority of it has only progressed to the degree that individual visionary patrons - including many in the audience here - have been willing to fund it over the years. It has been slow and frustrating, but the wheel is turning. The success accomplished for the field of cellular senescence must now be repeated for a half dozen other vital lines of rejuvenation biotechnology. Aim high.

Comments

Reason, do you feel like the tides have been changing in favor of SENS? You've been following this stuff for at least 10 years. I notice that Aubrey and a few others mentioned a year ago or so that "the SENS approach is becoming less contrarian every day, actually - many groups of mainstream gerontologists have taken it and made it their own" (something along those lines). Certainly in the scientific advisory board it's been good - Brian Kennedy being on it now when he was part of the anti-SENS crowd back in the MIT Challenge days is a good sign - but I sometimes wonder if that's just looking for some optimism, or if the increased popularity of SENS is actually true.

I also note that I don't believe there's been an overarching critique of SENS since the MIT Challenge, and even that paper said that MitoSENS was impossible.

Posted by: Miranda at May 4th, 2017 6:05 PM

@Miranda: Definitely, though as ever, it is slower than we'd like. The community has only just started in on building atop the benefits of being right about senescent cell clearance - there will be a lot of leverage there as things progress.

Posted by: Reason at May 4th, 2017 7:50 PM

@Reason

This is unrelated, but might fightaging have a RSS feed? I can't seem to find any.

Posted by: Lee Wang at May 5th, 2017 5:38 AM

Thanks!

Posted by: Lee Wang at May 6th, 2017 3:29 AM

"Each component of the SENS panel will have standalone value in addressing one or another disease of old age, and some of them are already in clinical trials."

Is there a list of these clinical trials. Which trials and where it is done and by whom.
Maybe even some websites.

Posted by: Pieter at May 7th, 2017 1:39 PM

@Pieter: All of the amyloid and tau clearance efforts for Alzheimer's are SENS approaches, though of course most are failures until very recently. A successful clinical trial by Penxtraxin for clearance of transthyretin amyloid took place a couple of years ago now. Senescent cell clearance trials officially begin this year for UNITY Biotechnology, though there is a fair amount of self-experimentation going on unofficially by the sound of it. Some stem cell work counts as SENS, though not very much of it, and we can argue over details on that. The allotopic expression of mitochondrial genes is in trials for the first gene via Gensight, though not with aging as an endpoint. That covers the high points that immediately spring to mind.

Posted by: Reason at May 7th, 2017 1:50 PM

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