Aubrey de Grey AMA Held at /r/futurology Today

Aubrey de Grey of the SENS Research Foundation is an advocate and scientist focused on advancing the state of rejuvenation research, progress towards therapies capable of repairing the cell and tissue damage that causes degenerative aging. He put forward the Strategies for Engineered Negligible Senescence (SENS) research proposals some fifteen years ago, and since then has raised funding, organized research programs, cofounded the Methuselah Foundation and SENS Research Foundation, and traveled the world to speak at scientific conferences and meetings of supporters.

Back when this all began, members of the scientific community were very reluctant to speak openly about treating aging as a medical condition, the press treated the prospect of therapies for aging as a joke, and the public at large gave no attention to the topic. Yet the potential was there, with many disparate branches of research into age-related diseases demonstrating even then that scientists understood more than enough to get started on meaningful therapies to repair the damage of aging. The problem has always been cultural: that no-one cares, that funding is non-existent, that few are willing to step up and speak out on the issue, that the status quo of suffering and disease is accepted. With the help of people like de Grey and his allies the last decade has seen a real sea change in the research community and the media, however, as well as in the actuarial and the futurist communities, and the years ahead will see that change in attitudes spread to the population at large. If we keep working at this by the mid 2020s I expect the average individual in the street to think of aging in the same way as he or she thinks of cancer today: a fearsome medical condition that causes great suffering, researchers need to work harder at fixing it, and charities raising funds for research are a worthy cause.

Over at the Reddit /r/futurology community today de Grey was answering questions in an AMA (Ask Me Anything) event. It is worth remembering that every Reddit community of any size is a collection of widely divergent interests. Thus /r/futurology is a mix of folk who follow progress in computing technology, basic income advocates, popular science buffs, futurists of all stripes, both for and against longevity enhancement, and various other less categorizable groups. So the forum can host a respectful AMA for de Grey packed by people who look forward to progress in rejuvenation research just a day after a long discussion on a recent aging research paper in which most of those involved were opposed to human life extension. It is a big world, communication is making it smaller, and we're all rubbing shoulders these days.

Ask Aubrey de Grey anything!

Buck-Nasty: I'm curious about how the advent of CRISPR affects the development of SENS therapies?

Aubrey de Grey: It's huge. It will be central to the delivery of the many SENS components that involve somatic gene therapy.

Buck-Nasty: Does it speed up the development timeline at all?

Aubrey de Grey: A lot, yes.

Jay27: Kind of a shame, because it looks to me like deep learning algorithms will be plowing their way through a million genomes in 2020. You'd think they'd yield some valuable genemod insights which can then be applied with CRISPR.

Aubrey de Grey: We don't need insights right now - we need implementation of what we already know or are developing. That's why CRISPR is so important.

Senf71: Is it fair for me to be telling my friends and others I tell about this stuff, that considering the $25 a month I donate to SENS and the many dozens of people I have educated about SENS and curing aging in general, many quiet successfully educated, that I may have personally saved the lives of 100,000 people at this point? Along that line is this something it would be good for you and your people to really emphasize during talks? To tell people that they can feel good about them selves for going out and advocating and donating even a meager amount of money because doing so means they are very truthfully saving the lives or 10s or 100s of thousands of people?

Aubrey de Grey: This is by far the best question yet on this AMA. Thank you! First: I think you can say something like that (depending on how long it's been that you've been sending us $25). I believe that $1 billion right now would hasten the achievement of LEV by about 10 years; you can do the rest of the maths, but it comes out to about $2 per life - and of course "saving" means a great deal more in terms of extra years than it does for other ways of saving lives, so arguably it's more like a few cents per life. And yes, I think I should emphasise this more. I probably will.

Spats_Mgee: Several aspects of your SENS proposal are essentially destructive in nature (removing intra/extracellular junk, killing errant cells, etc). Your proposal to deal with these problems involves utilizing enzymes found in other species to break down these molecular structures. I'm curious if you've weighed the pros and cons of this (let's say "organic") approach to the "inorganic" approach of using gold nanoparticles for targeted photothermal ablation of these cellular/molecular structures.

Aubrey de Grey: We've looked at this approach and we haven't rejected it out of hand. A big issue is penetration: how does one irradiate deep within the body?

Lavio00: I watched a video from you back in 2013 where you commented the announcement from Larry Page about Calico. You mentioned that Calico - if they're focused on early stage research - might highly benefit the battle against aging. What is your comment regarding Calico's research now that a couple of years have passed? More/less excited about their potential?

Aubrey de Grey: Cautious. They are structured perfectly: they are doing a bunch of highly lucrative irrelevant short-term stuff that lets them get on with unlucrative critical long-term stuff without distraction. But the latter may be getting too curiosity-driven and insufficiently translational. We'll see. Here "highly lucrative irrelevant stuff" = drugs for specific diseases of aging, "unlucrative critical stuff" = work leading to actual longevity escape velocity.

SirT6: One thing that has always struck me about your vision for extending human lifespan is that you don't seem particularly interested in attempting to leverage the molecular genetics of aging. Numerous animal studies have implicated a number of genes which may serve as pharmacological targets for ameliorating aging and age-related pathologies. Studies of human centenarians have also validated the idea that modulation of these genes or their protein products may be a viable option for extending lifespan. And from an evolutionary perspective, this seems to make sense - many genes exhibit antagonistic pleiotropy (good when young, bad when old), so inhibiting these genes/proteins as people age is likely to reduce the burden of age-related disease. I suppose you could argue that this won't drastically increase human lifespan, but it seems to be a far more tractable approach in the near term (clear molecular targets, easier biomarkers, simplified drug development etc.). I would be curious to hear your thoughts on the issue. Thanks!

Aubrey de Grey: You put your finger on it - tractability versus magnitude of effect. As I think you know, I subscribe to the school of thought that CR-mimicking genetic or pharmacological manipulations cannot to much in long-lived species. I don't want to suppress such research, but I do think that the field has been immensely harmed over the past 20 years by overoptimism concerning the CR-mimicking approach and consequent lack of interest in alternatives. Antagonistic pleiotropy has very little to do with this.

akerenyi: I believe that the distinction you make between SENS-type of research focusing on damage from ageing and research on age-related diseases (ARDs) is purely arbitrary and misleading. For example you correctly claim that ageing and ARDs are pretty much the same thing, but than go on the criticize research on ARDs for not focusing on the right thing, while even further you plan to use therapeutics coming from this research, like Alzheimer's vaccines for rejuvenation (correctly so). I think the reality is that research on ARDs does involve more basic, mechanistic work as well as more later-stage, symptomatic approaches, compared to your engineering approach. However, I think the former gave and will give the targets for SENS, like beta-amyloid or tau, while the latter gave us drugs like levadopa, which while being crude and non-definitive, did improve the quality of life of millions of patients, while stem-cell therapy or gene therapy is being developed. Please clarify whether you still think such a distinction is desirable or meaningful.

Aubrey de Grey: The issue is relative funding. Illustration: it is absolutely accepted that atherosclerosis, the #1 killer in the western world, starts with the inactivation of macrophage lysosomes by oxidised cholesterol. Yet, about two labs in the world are focused on that step. I'm very satisfied indeed with the amyloid-beta vaccine results - they eliminate plaques. Same with gene therapy.

jimofoz: Can you give us any updates on the research towards allotopically expressing all 13 protein coding mitochondrial DNA genes?

Aubrey de Grey: It's going really well. We've made big breakthroughs this year and we'll be publishing something soon.

jimofoz: How pleased are you that Gensight is now taking the allotopic mtDNA expression technology whose development SENS partially funded into stage III clinical trials?

Aubrey de Grey: Overjoyed. We funded the Corral-Debrinski lab early on. Our work is leaning heavily on their early discoveries.

Rdapt85: I haven't heard any development in GlycoSENS since the discovery of synthesizing glucosepane in the lab 2 years ago. How is it going?

Aubrey de Grey: It's tough as hell but yes, we are plugging away. Watch this space.

Comments

I'm glad you linked to this today, and I encourage people to read through it if they have time.

I thought this was interesting:

jimofoz:

Hi Aubrey, some further questions:

(a) Why do you think Peter Thiel has 'only' donated 6 million dollars to the SENSRF given that he is a billionaire. Is he on the fence about the SENS proposed therapies and do you think he will be sold and will go 'all in' before RMR (Robust Mouse Rejuvenation) is achieved?

(b) What is stopping you guys from using CRISPR on a mouse embryo to express all 13 mtDNA genes in the nucleus and then sitting back and seeing how this line of mice ages vs wild type mice? Even if you don't think Derinski's method of adding RNA tags onto the front and end of the mRNA will work for all 13 genes... just throw a hail Mary and do it and see what happens?

Aubrey de Grey:

1) Watch this space.

2) That's not how you build a rocket.

Maybe SENS will soon be getting much more financial backing from Peter Thiel? I know that's not too much to go off of, but it does seem hopeful.

He also makes some comments about aspiring to collaborate with Calico... and given their funding, that couldn't be a bad thing.

Posted by: Ham at August 4th, 2015 6:38 PM

I've gotta say, Dr. de Grey is refreshingly direct, particularly when compared to the usual mealy-mouthed people making vague promises.

(No, I didn't show up, as supporters without questions really had nothing to do there. I was wrong about who would be there; despite that other Reddit thread, the death cultists did not, in fact, come out in force.)

Posted by: Slicer at August 4th, 2015 8:46 PM

Given past speculation on this blog that mitochondrial mutations could play one of the larger roles in aging, I am looking forward to hearing about the SENS Foundations 'breakthroughs' in this area.

Posted by: Jim at August 4th, 2015 9:32 PM

Also Gensight is currently developing ND4 and ND1 and, I'd guess, ND6 but are using AAV2 as a vector which does not integrate into the cell's nuclear genome.

That is 3 out of 13 soon to be down by my reckoning.

http://www.gensight-biologics.com/uploads/images/Image2.png

Posted by: Jim at August 4th, 2015 9:52 PM

Gensight are additionally developing another interesting (but non SENS related) technology where they are using gene therapy to make damaged photoreceptor cells responsive to a specific light wavelength, then use a camera on a pair of glasses to project an image at this wavelength onto the retina.

However the glasses they are using are just of a standard sunglass type.

http://www.gensight-biologics.com/uploads/images/optoelectrnic-device.jpg

I can't be the only person thinking that they are missing out on a massive PR coup here. They should make the glasses into a band like that worn by Geordi La Forge from Star Trek!

http://www.startrekdesktopwallpaper.com/new_wallpaper/Star_Trek_The_Next_Generation_Lt_Commander_Geordi_La_Forge_freecomputerdesktopwallpaper_1600.jpg

Posted by: Jim at August 4th, 2015 10:05 PM

Thanks Reason,

I for one appreciate seeing a progress report with SENS/de Grey. It gives me hope that we just might have fundamental progress/change within a few decades on ageing.

Posted by: Robert Church at August 4th, 2015 10:59 PM

"Aubrey de Grey: We don't need insights right now - we need implementation of what we already know or are developing."

Thank you. That's why I like Aubrey de Grey that much.

Posted by: Waverunner at August 5th, 2015 2:28 AM

I'm looking forward their annual report that probably will come this month. Surely more detailed progress information will be there.

Posted by: Antonio at August 5th, 2015 2:38 AM

Slicer, I was kinda surprised to not really see any death cultists too. There was one guy who seemed like he was suicidal and wanted people to die faster, himself included, and used the max Planck quote about science advances one funeral at a time. And there was another one who said it could be beneficial for the individual but a detriment to society. Other than that it wasn't too bad on that end, which was surprising.

Posted by: Ham at August 5th, 2015 3:56 AM

Also, there were comments talking about moral and ethical concerns. I hate when people bring morals into it, like somehow thinking people should and need to die gives them the moral high ground over those who want to extend life. Is it really ethical to allow people to suffer through diseases of aging, when we can do something about it? I don't think it is, but it seems I'm in the minority.

Posted by: Ham at August 5th, 2015 6:01 AM

If these opinions or views are what we have to contend with, then... seriously? I don't even know. I'm going to just post my conversation (sorry it's kinda long) I had with someone here... the TL:DR is pretty much irrational fear of people being "immortal" and destructive and screwing over non "immortals". Sigh.

Redditor: If you take the conceit of there being successful longevity, for instance you being the one who is the first immortal, would you really want that status to be known? Would you not be vastly more safety conscious? Wouldn't your behavior in regards to your own diet, exercise, and overall health be entirely different? YOLO would not just be laughable to you, it would be similar to how you view people who actually play russian roulette.

Death is an incredibly universal contributor to nearly all decisions we make as mortals, removing it reveals all new questions that we have never even thought of, much less asked.

My response:
To be fair, the use of the term immortal is pretty misleading here. It's not like this makes you unable to die. The goal is to keep people healthy, with longevity being a side effect like Aubrey said. I really don't think people would change their everyday lives much. Besides, getting something that will increase your healthspan probably won't keep you from getting obese if you eat like a slob, cancer if you smoke, or a plethora of other diseases that can kill you.

Sure, society would end up changing, but it's not like there aren't some changes needed already. I also think it would be entirely optional, so those who were against it or didn't believe in it would not have to take it... but really, who wants to not be healthy and young feeling. Social services probably wouldn't have to be extended nearly as much either if people were healthier their entire lives. Alzheimer's care alone is estimated to be around 1 trillion per year in 2050... and that's just one disease.

And I do think people would care more about things like global warming if they knew they were going to be around longer and have to confront it. The attitude that many people have now is that it isn't their problem to deal with. Well, what if it was?

Redditor:

Yes, that's the point I'm making, only with a different conclusion. If you aren't going to die from natural causes, wouldn't your attention shift to maximizing the condition of your physical form? It's a standard assumption that you're only alive for a set period of time, only a small amount of which is optimal, so YOLO makes sense. It's insanity if you live forever. It would be like someone today literally living as if today was their last day on Earth - big mistake if they have a few decades to go.

Yes, but longevity doesn't address quality-of-life. It's focused on mitigating or eliminating death through natural causes. You could live forever as a paraplegic, or with severe autism, for instance. Social services would either need a fundamental redesign or would segment to "mortal" and "immortal" - the exact sort of thing I'm talking about when I'm saying things wouldn't go well.

Perhaps, or perhaps immortals would have a view that Earth is a birthing chamber, to be used to get off-planet asap. Kepler is only 500 light-years away. That would a reasonable goal for an immortal. Earth could be discarded like a placenta, or like "the house I grew up in." Again, it's very difficult to imagine what someone's views will be if you remove mortality as a given.

Posted by: Ham at August 5th, 2015 3:12 PM

@ Ham / 1st comment:

That could also be a standard reply, as in "we'll get more funding from him eventually, he told me so, but there's no definite timeline".

But I sure would prefer this to be hinting that Peter Thiel, after having made a cautious (though relatively important) initial funding in Aubrey's endeavour, is satisfied by the impetus he gave. That he remarked the SRF is working diligently on its goal and is thus worthy of getting more money.

And I believe this would be an important gesture from Thiel.

First because, of course, direct additional funding is crucial.
But also because it would fuel the race against death through better public awareness.

Indeed, now that the public is getting more acquainted with big engineering against ageing (see Calico and the PR that ensued), any anouncement of Thiel committing again serious money in the longevity sector will be met with increased echo.
It will reinforce the increasingly accepted idea that rejuvenation is a serious business - figuratively and literally. (The concept of rejuvenation is debated, yes, but 10 years ago it was dismissed. Simply dismissed as a mere joke. That's a positive progress). In turn, this move could trigger more funding from people/institutions who were either unaware or still on the fence.

Posted by: Nico at August 6th, 2015 6:01 PM

I have to say I trust Mr. De Grey when he says these treatments would be available to all but I am afraid he will not be able to make that decision stick in the long run.
Perhaps if SENS has in its rules that such should be the case specifically, then fine. Yet, SENS can be overruled too, in practice, if not on paper.

How about the laws that exist at SENS headquarters, I think UK is where they are based? I believe if the success of their research is that close, then someone should draft a proposal to make it into law that everybody regardless of their financial situation is entitled to the treatments.
Why not, since the USA has recently passed a law regarding asteroid mining, and asteroid mining hasn't been accomplished yet?

Posted by: Anonymouz at August 7th, 2015 10:39 AM

And as an afterthought, do we really want everybody to have tremendously increased lifespans and health for the sake of not having them retire?
Imagine engineers working 16 hour days for millenia! Wow, is that something to make people want longer life or is that just a ploy to get them to commit suicide?
Surely something more hopeful than working to pay for youth....?

Posted by: Anonimouz at August 7th, 2015 10:51 AM

Anonimouz:

AdG doesn't think treatments will be available to all because SRF will enforce that. The reasons are different: (i) geriatric care is too expensive now, and more so in the future, so it will be a suicide for any nation to allow expensive prices for rejuvenation treatments, (ii) pensions are also too expensive, and more so in the future, so, again, it will be suicidal to allow expensive prices or to not fund rejuvenation research.

"And as an afterthought, do we really want everybody to have tremendously increased lifespans and health for the sake of not having them retire?"

WTF? We want that for the sake of not being decrepit and die after decades of suffering and misery.

"Imagine engineers working 16 hour days for millenia!"

??? Engineers today don't work 16 hours day. Why will they do so in the future??

Posted by: Antonio at August 7th, 2015 11:25 AM

First off, in the United Kingdom, everyone, regardless of financial situation, is already entitled to treatments. It's called the National Health Service. Extending the NHS's remit to fundamental preventative maintenance of human beings (i.e. the treatments that make them not degenerate into horrible, decrepit caricatures of their former selves) is not an entirely large leap. There won't be any act of Parliament; rejuvenation treatments will just become part of standard of care. It's the United States that might pose problems, because the two parties each have their own psychoses, but if the choice is between paying out the wazoo for Social Security forever and just making people not need it, the country'll get around to picking the latter.

And speaking of which... what is wrong with people's lives that they independently start going "Oh no, I just realized, people would have to work as long as they live!" as each one of them thinks it up? Seriously, how bad are people's jobs, how desperate are their situations, that this is actually a common concern? "I'll be dying slowly over a period of decades, my body and mind eroding out from under me... but at least I won't have to work anymore!" If your life is genuinely that bad, then you need to start making changes now instead of waiting for slow death to take it all away from you.

Can you imagine a Methuselan engineer's resume printed out on 8 1/2 x 11? *THUD* "I asked for the short version!" "Oh, this is the short version, do you want the long version?"

Posted by: Slicer at August 7th, 2015 1:11 PM

To add to Slicer's opening paragraph: and in the United States, everyone over the age of 65, regardless of financial situation, is similarly already entitled to healthcare. Any rejuvenation treatments approved for any licenseable condition will be available to such people, and it's just a matter of time before sufficient medical evidence, electoral pressure, economic rationalism, and humanitarian concern combine to make them available to younger persons. The next step will be a PEPFAR for SENS.

Posted by: Michael at August 7th, 2015 3:54 PM

"it's just a matter of time before sufficient medical evidence, electoral pressure, economic rationalism, and humanitarian concern combine to make them available to younger persons"

I hope so! It'd be the logical choice. If a complete suite of rejuvenative therapies becomes the covered standard of care, how long will the government cover basically unaging retirees before that matter of time comes, before someone wises up and realizes that any arbitrary age cutoff is silly? Given the sheer power of political inertia (more on that below), it might be some time.

For people not familiar with the subject: Senescence can do incredibly bad things to people before they reach 65, particularly if they don't know how to take care of themselves. Regular FA! readers who exercise daily and eat minimal calories and plenty of senolytics will probably be only moderately touched by the time they reach that age, barring bad luck or calamity. A 350-pound habitual smoker with latent viruses in his system? Not so much. So until someone wises up, "Just make it to 65" will be common advice among lower-class 50-year-olds.

Well, more than it is already, as this is actually a worsening of an already extant problem: a lot of people need to make it to 65 before they can actually afford to see a doctor, even if they have high-deductible "insurance". Someone with Stage 1 cancer might ignore it until he turns 65, by which time it's not Stage 1 anymore. Happens all the time.

Adding to the fun is the fact that rejuvenation will not come all at once, because aging is not one process. Someone with his senescent cells regularly cleared, his foam cells ripped out, and his mitos repaired might still be tormented by glucosepane. And we still don't even have the beginnings of a real cure for AD (no, these flailings around with amyloid clearance don't count).

In my last post, I forgot about the "Screw you, my life is over" folks; yes, those exist, in numbers, and we've already seen their prototype in these comments. A lot of people who are perfectly capable of working thanks to becoming rejuvenated might demand to stay retired forever, economic sense be damned, especially if they're only partially rejuvenated. Unless we've gone total post-scarcity robot-everything by that point, the US could easily end up like Greece, which has lots and lots of retired healthy people already. (And so could all the other nations for that matter, unless they make retirement a disability-only concept fast.)

The sensible thing to do would be for the President to go up on stage and go "Okay, here's your choice: either we pay for all the available longevity treatments and only let you retire when you're actually disabled due to something we can't cure yet; or, we pay for your retirement no matter what but don't make you younger in any way." There's no way anyone could get elected or re-elected actually saying that, but that's what will have to happen sooner or later, or the country just debt spirals to hell (again, barring a post-scarcity economy).

They'll have to get people off indefinite payments and onto indefinite lifespans sooner or later, but the transition is not likely to be smooth, no matter how rational it seems that it would be.

Posted by: Slicer at August 7th, 2015 7:28 PM

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