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Aubrey de Grey on Progress and Timescales in Rejuvenation Research

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.

Anti-Aging Pioneer Aubrey de Grey: "People in Middle Age Now Have a Fair Chance"

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.

Comments

To me the last paragraph says it all. People of middle age should have a 50/50 chance of achieving Longevity Escape Velocity in the next 20 years. I'm planning apply as much of the anti-aging therapies as they come out.

Posted by: Biotechy at February 1st, 2018 3:26 PM

Biotechy: ... provided adequate funding is available.

Posted by: Antonio at February 1st, 2018 4:50 PM

@antonio funding is improving rapidly at the moment

Posted by: Scott emptage at February 1st, 2018 7:01 PM

@Scott it's improving but let's not get carried away here, things have improved recently and things continue to get better for the field funding wise but we have a long way to go before we are out of the woods. We should not get complacent or relax for a moment on the funding and advocacy front.

Posted by: Steve Hill at February 1st, 2018 7:12 PM

He's always stated that its a 50/50 chance for medicine to have aging under comprehensive medical control with the SENS platform. We will likely see other more modest forms of life-extension before we see SENS 1.0. They probably won't be anywhere near as effective, but we'll probably improve healthspan. That will hopefully ease some suffering.

But he's been surprised by a few things as well. Like how much of an impact senescent cells have on so many diseases of aging. Its one of the major pillars of aging,

And Reason is raising some excellent points about what technologies 'stack'. We really haven't touched that at all. You can bet they are looking at it though. No way people like Alex Zhavoronkov aren't using every scrum of data available to try to glean the best combinations to try. We also know that George Church is taking a multi-pronged approach with his work. He's resetting telomeres, upregulating NAD, and throwing whatever he can at the wall to see what sticks.

Aubrey's approach is probably the best approach, but its not the ONLY approach. There is no way he would be at AGEX if ITR won't be beneficial.

Best of all, love him or hate him, Trump is pushing "Right to Try" policy. If I'm on deaths door and I get a shot at ITR or something, I'm in. Most of us would be up for it as a Hail Mary pass.

But once again, it doesn't matter. The Wall is coming by 2030. Either we have effective ways to reduce disease by then or it won't matter anyway. Economic collapse has a way of killing research funding.

Posted by: Mark Borbely at February 1st, 2018 8:35 PM

Hi all ! Great interview. Just a 2 cent.

I'm also very curious about these 2021-2030 trials in humans, this will tells a lot and finally the cat will be out of the bag about their effect, in humans (not cats (or mice) or cats that like mice or rats or other rodents scientific studies study away including the cleavagy naked ones (Naked Mole Rat (why have a fur coat when you can have skin (cleavage) NMRs know how to live 'light' and show their skin moles (ironically they never have cancer/skin moles))))).

Seriously, I hope this turns out great and AdG is ever more confident, it is felt through and through these subsequent interviews. There has been many great donations (million dollars of bitcoins), thus the future is looking good - big spenders and coffers are noticing this, donations seem appropriate when you die anyway; so why not give (your) money (some) to accelerate rejuvenation and make you Still Alive with all your money/and you can make more because you won't be dead. That's the whole point . Dying rich is mostly pointless (although scrooge, ethicists and fatalists would object, also the heirs/people who inherit that family money' (but that's really awful, to prefer testament will-money - over your parent living longer by rejuvenation; like your parent being Still Alive...). There is a renewed energy about our future, it is now more than possible to have longer lifespan, in health. It is not some fiction (in the collective heads of many) like it was 20 years ago, it is much more talked about seriously and as a true possibility; that we must fight for. Because our life depends on it (if we do value our life because it has an end).

I wrote a response (though don't have the account anymore because of privacy thing asking real name and my user is CAN-anonymity after all) on Quora to a question that was like : ''Why do we die/Why should we die/What is the meaning of this (life) if there is one ?'' you know those type of questions (very ethical philosophical). I explained that the future was SENS and explained to them the whole thing, why it is not bogus and bs, and why it is Possible to believe that one day we will live extreme lifespans because we will keep our health and mortality brought down to (near) 0 and thus, aging pushed back through rejuvenation.

There was upwards to 200 'likes' to my answer, demonstratingt that people are not so 'fatalist' when they realize that life acn be lived Longer, Healthier and Death can Wait....
for many more decades (I would prefer centuries, heck milleniums, we're not there yet).
Because on that website it is loaded with two kinds of people : fatalists and non-fatalists.
You realize quick the 'embrace death, don't be scared or selfish, go forth and take the plunge'..and the other side 'we are for extreme lifespan in health and even some of us wish the I-Word (Imm.) Eternal life; no we are not crazy we read scientific litterature and base ourselves from provable lab research; if you want to call us selfish or unethical go ahead; we'll counter by saying you also don't make More Sense, than us as if Your Morals are the High Ground and Decider of All Humanity'). It made for interesting responses : 3/10s were fatalists like 'stop believing in life start believing in your death, do your duty die good human (dead)' and 4/10s were just like 'i don't care/dunno/whatever/eternal life is magic and bs' and 3/10s were 'Can I Not Die - Ever - and, Forever (Live)'.

The main sentiment was that people are curious/dubious but it could be Something great if it did work.

''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. ''

''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 ''

''Remember - a 50/50 chance of getting to Longevity Escape Velocity within 20 years''.

I think these chance estimates are very 'ballpark' but that is what estimates/odds are. I feel they may be a bit too generous and optimistic; and I would like that but I think this is on 'the best scenario' estimates, not the worst. I prefer safer estimates.

What is more realistic (I feel) is :

50/50 (50% either way) chance to obtain 7 therapies in 20-30 years (I put extra 10 because it's slowmo and funds coming in are the rate limitor; along with FDA/instauration, which you may need to add another 10). Which means us living people in the 30-50 years old brackets will be 60-80 years old at latest by then.

10/100 (10%) chance of reaching Longevity Escape Velocity in 30 years, because certain limits or problems are still not resolved and as it is we will need 50some therapies to cover it all/aging is that complex and deep. That is generous, sometimes I feel it is more 1/100.

000000000.1/100 (000000000.1%) chance of human born (or soon in next 25 years) to live to a 1000 years old with any therapy of the future.

60/100 (60%) chance of SENS and other therapies not making LEV ever not even in a 100 years, but they would increase lifespan in 20-50 years extension; 60-70 extra is pretty max for it is nearly half of a super super centenarian.

60/100 (60%) chance that the rejuvenation sees unforseen problems that render the 'rejuvenate to 40 year old, rinse repeat' does not work à la car-repair analogy; repair 'just enough damage' to matter and you should espcape mortality.

60/100 (60%) chance that SENS suffers some problem (him leaving) or it is 'abandoned' kind of like 'abandonware' (a site where software go to end life, the software graveyard)). The first results will tell a bit about the furure - will it strive or fail - good results help a lot (as in a mouse that is rejuvenated) if not, and with many problems, it will end up like many anti-aging suppléments - an afterthougt (forgotten as 'an idea that 'once was' but never came to be (and failed like many abandonned crowdfunding kickstarter campaigns))).

Let's hope for the better odds (I know hoping can be hopeless but not much else to do besides donations/talking about it/it's just like a 'train/plan' you Watch 'unfold' from afar and hope it works as planned. Many kickstarter campaigns fail to deliver and later announce 'it's over. we ran out of money or we could not deliver/we failed'; end of story. The backers feel ripped off for they donated so much (and sure a donation is 'given' without 'asking' anything in return...but deep down you donated because you hoped that it would work/'change things' in society'/you supported that cause for it to 'happen' not fail and give 'free money' 'in the air' 'throw it out the window' to a 'dead end' endeavor).

Just a 2 cent.

Posted by: CANanonymity at February 1st, 2018 10:23 PM

Mark said: "And Reason is raising some excellent points about what technologies 'stack'. We really haven't touched that at all. You can bet they are looking at it though."

I saw the other day an old talk by AdG (from 2005?) stating that if we only cure one of the 7 categories, we would get a life extension approximately equal to the mortality rate doubling time (7-8 years). But in later talks he never says that, simply saying that the effect would be small or that he is not sure.

Posted by: Antonio at February 1st, 2018 11:12 PM

My own guess is that senolytics alone would give us at least an extra 5 years, probably 10 too. After all, we have been increasing lifespan by around a couple of years per decade even without doing anything about aging.

I'm more worried about neurodegeneration. Lots and lots of money have been poured on AD research, the amyloid hypothesis is almost three decades old, and still no drug in the clinics.

Posted by: Antonio at February 1st, 2018 11:23 PM

CANanonymity has so much pessamism

Posted by: scott emptage at February 2nd, 2018 9:36 AM

@ Scott

Well... truth... the pessimism is kinda well deserved at this time. Lets look at the massive let-downs we've had to deal with over the history biotech, medicine, and anti-aging technology.

How many times have we cured a litany of diseases in animal models, but we hit a brick wall with humans?

How many dollars have been spent on anti-aging 'hope' and we got nothing out of it. (Resveratrol is one).

How long has poor Aubrey been out there giving the SAME talk and answering the SAME questions. Cracks are appearing now... the message is starting to sink in.

Also, this community bends to the negative because we are rational. To want to avoid aging and death are the RATIONAL responses to our condition, and that brings me to my next point.

There is a MASSIVE mood of pessimism out there right now when it comes to just about everything. In fact, its so high, that objectivity is a real endangered species right now. Its not just in medicine. Its pervasive, and with good reason. Our media do a damn good job of painting everything as bad and bleak and horrible. They want eyeballs, they want clicks to boost revenue. The reality of things are not that bad in every aspect of existence. In some (Say inequality) yes. They are bad, we have the stats to prove it. But in others, (Say, the ozone layer repairing) the pessimism does not match reality. All of Western society needs a prozac enema. The whole planet is collectively depressed.

The cynicism out there on the average message board is painting a pretty bleak picture of just about everything right now. Its partly the media, and partly the state of the world. We as a species desperately need a win. Proof that things CAN get better. Managed decline is no longer a political winning platform. We want change, and it looks like we may get it.

My posts try to be positive (With some kind of proof) to balance out the negativity. The truth is, anyone under 50 right now (Possibly older) is probably not going to suffer the way their parents and grandparents did. That much is pretty much baked in right now, and if asked to elaborate, I will.

LEV is another matter entirely. If you ask me FLAT OUT, and I'll admit, its pure speculation on my part, I think our odds are better than 50/50. Not 100%.. But I would put it at 70/30. I'll break it down if asked, but the more I'm looking at certain research, the more I believe that Reason's "Stacking" concept works on multiple levels.

Anyway. Bottom line, we in the community are a tough sell. We're used to being fringe, we are used to let downs. We are used to achingly slow progress.

That is changing. I can objectively see it.

Are we there yet? Nope.

Has the tide turned? I think so. I think so bigly, but I think we can do better. I know we can do better. And with our star leaders and our community, we can do it.

SO SAY WE ALL :)

Posted by: Mark Borbely at February 2nd, 2018 1:07 PM

@Antonio: You should take a highly bioavailable curcumin supplement for your neurological concerns until a life-extending drug becomes available. Curcumin stimulates production of essential brain growth factor BDNF that promotes connections (neuronal placticity) between brain cells and enhances outgrowth of neurites.

Posted by: Biotechy at February 2nd, 2018 1:07 PM

Future predictions are extremely difficult; too many variables and unknowns. I hope de Grey is right about a 50/50 shot for the currently middle-aged. Strikes me as a bit optimistic, but there's no way to know. Whether the chance of reaching escape velocity for those reading this is 1% or 75%, it doesn't really change what we must do though: (1) live our lives as healthfully as possible (2) donate to and positively promote SENS as much as possible.

Posted by: kel at February 2nd, 2018 1:25 PM

@Mark Borbely: Well said.

Posted by: TL at February 2nd, 2018 1:53 PM

@mark borbely thanks for that comphrahensive comment. Very good points thanks

Posted by: Scott emptage at February 2nd, 2018 2:01 PM

Biotechy: No supplement or drug has reliably proven any beneficial effect on Alzheimer's progression.

Posted by: Antonio at February 2nd, 2018 3:43 PM

Well of course curcumin also also tends to put out some of the inflammation and oxidative stress in the neurological system as well. It is probably the best single supplement you can take for your neurological problems.

Posted by: Biotechy at February 2nd, 2018 3:57 PM

@ Biotechy and Antonio

If there is a way we can make aging a unitary disease in medicines eye... AD is probably the door to do it. I don't think we have ever had such epic failure in research given the funding in our entire species history. Money down a hole. Worst thing about it is the window of time we have to do something about it is closing so fast.

Its mind boggling the wall we keep hitting.

Posted by: Mark Borbely at February 2nd, 2018 4:00 PM

@ Antonio and Mark: In summary, Life Extension said in their Winter 2017-2018 Edition "Promising studies are emerging on natural treatments for Alzheimer's, and curcumin is a leading star. I am simply saying, try it on an interim basis until we get something better. Incidently, there are other drugs already in advanced trials for AD treatment, for example one by AVXL.

Posted by: Biotechy at February 2nd, 2018 5:44 PM

@ Mark Borbely : I quite agree with your assumption that "anyone under 50 right now (Possibly older) is probably not going to suffer the way their parents and grandparents did."
Just a few minutes ago I read an article where two oncologists said that the five-year survival rate after a cancer has been diagnosed is projected to be 70% to 80% by 2030 (as opposed to 30% in 1970 and 50% in 2000).
It's only a projection, but I think it indicates the level of confidence displayed by cancer researchers. Again, they might be overconfident. But somehow it's more reassuring than if they were pessimistic !
And so, if cancer can largely be brought under control, a good deal of suffering will have been gone.

@ Kel : 50/50 for a 50 year old sounds fair. Say, people reach the age of at least 70 : that leaves 20 years to reach LEV. Awareness is growing, innovations and discoveries are compounding... give it two decades and LEV might indeed become a reality.
Also, I agree entirely with your two recommendations. Being healthy and donating/advocating are what we can and must do right now.

Posted by: Spede at February 2nd, 2018 6:01 PM

@ Antonio, "My own guess is that senolytics alone would give us at least an extra 5 years, probably 10"

Seems to me, if we can use senloytics within 10 years, that alone should help older people reach LEV before it is too late. Or maybe I am being a bit optimistic.

And, once this is available for the public and it is well publicized, then I would think rejuv research will become as well funded and popular as cancer research is now.

Posted by: Robert at February 2nd, 2018 11:43 PM

Biotechy said: "Promising studies are emerging on natural treatments for Alzheimer's, and curcumin is a leading star."

Talk is cheap, show me the data.

Mark, etc.: Don't take me wrong, I know the fast progress biogerontology and regenerative medicine are experiencing, and the growing funding and awareness for SENS, but OTOH not all fields seem to be advancing at the same rate, and walls in translation can always appear.

Posted by: Antonio at February 3rd, 2018 12:12 AM

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