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The Actuarial Press Interviews Aubrey de Grey

An interview with Aubrey de Grey of the SENS Research Foundation appears in the latest edition of the Actuary. This is in connection with forthcoming appearances at actuarial conferences, something that has long been a regular occurrence in de Grey's schedule as one of the more important advocates for rejuvenation research. The actuarial community is a good target for all advocacy relating to aging research, not least because they are already half-way bridging the gap with their own projects, aiming to better quantify the prospects for extended life spans through progress in medical science.

The profession of actuary is a node that connects medicine as practiced today, medical research and development for tomorrow, and the staggering sums of money that move through the global insurance and pensions industries. They are among the most ready to hear the story that great uncertainty lies ahead for the trend of increasing life expectancy, with the potential for radical gains should rejuvenation research programs like SENS move to the next stage of funding and pace of progress. SENS or something like it will happen, but the timing is very uncertain because the bootstrapping process that ends with taking over the medical mainstream is still in its early stages. At this point a couple of rejuvenation technologies are in early commercial development, but research funding is sparse for the rest and they remain years away from realization even if all goes well. The other uncertainty is that no-one has yet deployed SENS-like therapies based on repair of damage in humans: the effectiveness of the first of these, such as senescent cell clearance, at the outset, or five years in, or after a decade of improvements, is a question mark. One of them could add five or ten years to human life expectancy, a very large outcome for a treatment undertaken every few years, or it could improve health but do nothing meaningful to life span because other causes of aging lead people to die on about the same schedule.

While far from all actuaries are paragons of rationality when it comes to rejuvenation research and the prospects for change, a sizable fraction have become increasingly willing to hedge their predictions over the past decade, and industry voices have warned that a time of uncertainty lies ahead. Technological progress, and the great sweeping change now underway in the research community, from trying to patch over the consequences of aging to trying to repair the causes of aging, will make twenty year and longer life expectancy trend predictions meaningless. Actuaries have been speaking on this topic for some time now, but it isn't a message happily received in all quarters. Change in the insurance industry will come but slowly, and there will no doubt be entirely unnecessary chaos and destruction as we progress towards the medical control of aging and the greatly increased healthy longevity that will accompany it. No tears should be shed for that outcome, achieved by those betting against progress, save for the fact that losses will no doubt be socialized and the taxpayers will wind up footing the bill.

Lifelong learning

Dr Aubrey de Grey is a prominent biomedical gerontologist and chief science officer of the SENS Research Foundation. He is editor-in-chief of Rejuvenation Research, a Fellow of both the Gerontological Society of America and the American Aging Association, and sits on the editorial and scientific advisory boards of numerous journals and organisations. "You know, people have this crazy concept that ageing is natural and inevitable, and I have to keep explaining that it is not." His views on ageing are simple. "The human body is a machine with moving parts and like a car or an aeroplane, it accumulates damage throughout life as a consequence of normal operation."

Historically, efforts to postpone the ill health of old age have focused on finding ways to clean up our metabolism so that we accumulate damage to the body more slowly. About 15 years ago, de Grey had a 'Eureka!' moment upon realising that the most practical way to achieve this would be to find ways to repair the damage rather than looking to slow it down. "I realised we can classify different types of genetic damage into seven major categories, for each of which there is a different repair approach". This is the focus of the SENS Research Foundation. "We have all these diverse projects across various strands of research that we think need to be done, and because we are an independent non-profit charity, we have the luxury of being able to work on the hardest problems."

Although some of his views are met with scepticism and disbelief, he feels that the scientific community is become more accepting of his ideas, citing a recent breakthrough publication in one of the world's leading scientific academic publications. "As time goes on, our progress becomes more significant in proving the feasibility of my ideas. When I first started talking about these, people found them heretical and there was a lot of denigration from the scientific community, but I've gradually won them over. Other people are also making progress in actually implementing what we're doing. Just recently, an important US paper came out that showed you could extend the lifespan of mice using a particular type of damage repair that we'd been talking about for a decade."

If de Grey's predications are solid, what does he think this means for the actuarial profession? "I sympathise with the actuarial profession, because the fact is, the people who pay you to do your jobs really don't want to know the truth." Obviously, if his predictions come to fruition, there would be enormous implications for our industry; life and pensions in particular. Giant changes in life expectancy are likely to spark a renegotiation of pension contracts, as well as the way we approach our healthcare system, state benefit system and provide insurance. De Grey refused to be drawn on the wider impact that successfully achieving his goals could have, commenting: "I think it is foolish to speculate on what society is going to be like, even in 20 years, let alone 200 years from now. So many things are going to be different. The only thing we can do is prepare for as many alternative possibilities and consider how we might minimise any problems that might be created as a consequence of solving the problem of ageing." He believes dwelling on the bioethical considerations is missing the point: "We have to recognise that the problem we have today is enormous. Therefore it's critical not to be intimidated by the prospect that we have too many people, or living longer might be boring, and not let those considerations actually slow us down in terms of the development of medicines that get ageing under control."

De Grey readily admits that the likelihood of his research successfully extending his own lifetime is low. "As for any pioneering technology, the timeframe is extraordinarily speculative. Nobody has the faintest idea how long it's going to take. I put it at 20-25 years from now when we have a 50-50 chance of getting to a decisive level of comprehensiveness that works, which I've called longevity escape velocity. If we do get there by then, I've got a fair chance of benefiting. But I have absolutely no doubt there's at least a 10% chance we won't get there for another 100 years because we hit new problems that we haven't thought of. So if I look at my own personal prospects, or the prospects of any other particular person, the timelines and uncertainty result in this all being very speculative."

Comments

Hi there,

''De Grey readily admits that the likelihood of his research successfully extending his own lifetime is low. "''

I wish him great luck on his project and therapies. I am surprised he is being more honest with himself, his own life/reversal of his own age by his own work, being modest/reasonable in own expectations of one's own work outcome and not fooling anyone with overexaggerated grand pertained therapy results in the immediate. But rather, as I had guessed by a large post I made a while ago, it would take 50 to 100 years, 50 lucky low possibility and likeliness, 75 possible but unlikely, 100 possible and much more likely. In more than a 100 years, near-immortality/near-eternal life by repeated rejuvenation is likely. Below 100 years, not likely.

''
As for any pioneering technology, the timeframe is extraordinarily speculative. Nobody has the faintest idea how long it's going to take. I put it at 20-25 years from now when we have a 50-50 chance of getting to a decisive level of comprehensiveness that works, which I've called longevity escape velocity. If we do get there by then, I've got a fair chance of benefiting. But I have absolutely no doubt there's at least a 10% chance we won't get there for another 100 years because we hit new problems that we haven't thought of"''

''Nobody has the faintest idea how long it's going to take. I put it at 20-25 years from now when we have a 50-50 chance of getting to a decisive level of comprehensiveness that works''

By my guesses, not nobody : P , everybody with no knowledge can make up numbers but I used some true variables to come up with 100 years number.
A decisive level of comprehensiveness that works, I'm not sure what he means, but I'm guessing 'good enough', 'we understand our stuff enough' that we can make the rest of the therapies from now on. In 20-25 years, he and his SENS will not have All the 6 or 7 therapies made. If he implied that, he forgot his own longevity paper where he said the first therapy will take 25 years rough. And then it will be quicker/easier/more experienced for new ones..so a 6 years wait for each other new therapy. Totaling more than 50 years. I think he meant just for the first one that's it, to have some kind of 'direction/momentum' to create the 6 others.

''...which I've called longevity escape velocity.''

It's good he remembers (of course : D...he wrote it), but he is standing by his research paper. Although, I clearly 'Sens'e (pun intended, had to : D, that he is trying to not make extreme outlandish claims, because he knows his longevity escape velocity paper would allow immortality by rejuvenation; which does not sit well with people (like the fatalists) who don't believe in rejuvenation, as we wish, that could allow eternal life. And he knows that everyone knows his SENS therapies could allow that, so he doesn't want to give false hopes if it fails to even rejuvenation all that much; and heck, never give immortality/eternal life either (far-fetched) - and on the other side; well..it Could give eternal life; and that is Also a problem for some/unwilling society...talk about hands being tied behind your back! He definitely is Agora (ancient greek woman) or the Gallileo/Leonardo Da Vinci (renaissance biologist/inventor/painter/sculptor...) of the modern time (both Agora in antique Greece, Gallileo, later on in Renaissance, wanted to prove that the Earth was round, the Vatican Italian religion authority refute that, forbid him to say that, locked him up, told him to burn his propaganga
'sci-fi' papers and if he spoke/publish that to indoctrinate middle-class, he would die burned as heretic on the burningstake for spewing heresy 'false science defying religious order'. He kept shut and lived, but his papers were true and he, and her, changed science forever and our society. In a SENSE, that is what De Grey's SENS is all about, martyrdom, and that is what De Grey is. History repeats itself, martyrs again. Martyrs die to become 'martyr' status, with SENS no one dies, so we will have a new Living Martyr : ).

''But I have absolutely no doubt there's at least a 10% chance we won't get there for another 100 years because we hit new problems that we haven't thought of.''

That's what I have been saying, the longevity escape velocity paper doesn't factor in these problems that will happen and will drastically slow down the realization of the project. His 10% chance is way too small. Sorry, but I believe that number to be closer to 50% or more. There really is 1 chance out of 2 we won't get there, at least.

''So if I look at my own personal prospects, or the prospects of any other particular person, the timelines and uncertainty result in this all being very speculative.''

That's reasonable, still it does show that that uncertainty is why it Will take Much longer than hoped, and may take up to 100 years. When things are less uncertain, things speed up, doubt slows thing down. And yes, I was told, nobody knows...and it could happen in 30 years or 300 years for all we know...but being realistic/pessimistic : D ;)...joke...rather than
wishful/optimistic. Most likely, the likeliness, is that that it would take 25 years for full rejuvenation is slim. That it would take 50 to 100 years, the likeliness is less slim, and more 'Real' along what progress/research/time it takes to make 'things happen' in society (with so many hurdles : FDA, fatalists, no cash, therapy lackluster/fail, ....)

Posted by: CANanonymity at April 9th, 2016 2:10 PM

This is significant because Aubrey de Grey himself is admitting that our chances are extremely slim. I've said before that none of us are going see longevity escape velocity in our lifetimes, but people have attacked me, called me a troll, taken me to task for daring to insinuate that I know more than Aubrey de Grey. Well, now de Grey is agreeing with me. Sure, he's allowing for the possibility that it can still happen in his own lifetime, but he's being far more honest than most other futurists about what the odds are really like. It actually sounds like he's trying to let people down gently, lower their expectations. It sucks to be disappointed, and I sure wish I had been born 50+ years later than I was, but I've come to terms with it. It's the ones who have yet to accept the truth that I feel bad about.

Posted by: MissKaioshin at April 9th, 2016 4:54 PM

It would be great if Michael, or someone else would be able to address your comments regarding that research paper that you keep referencing or the variables on 100 years you mention. If it's the one I'm thinking of, isn't the paper almost 10 years old at this point? I'd be interested to see if they still stand by that paper.

Also, Aubrey has pretty much said the same thing about it potentially being 30 years, or 100 years since SENS has been around... so what are you getting at, exactly... besides you being your normal charming self?

Posted by: Ham at April 9th, 2016 5:20 PM

"I put it at 20-25 years from now when we have a 50-50 chance of getting to a decisive level of comprehensiveness that works".

He is 53, which even at today's mortality rates means that he has a good 70% chance of surviving until the day when there is a 50% chance that comprehensive rejuvenation is possible.

So how is "the likelihood of his research successfully extending his own" life expectancy "LOW"? The troll is obviously beyond comment, but I am surprised by the author's gross misinterpretation of de Grey's words: it seems that some people's disbelief in the possibility of age reversal is so ingrained that they let knee-jerk reactions get in the way of performing a simple calculation.

Having said that, I wish that de Grey revised his forecast downwards since he has been saying that aging will be under decisive control in 25 years for at least a decade. This flies in the face of a number of very important scientific discoveries such as CRISPR Cas9 (in 2003 de Grey himself said that the fact that gene therapy was "still rather black magic" was a major obstacle to the implementation of SENS) as well as the existence of therapies for which there is proof of concept (e.g. senescent cell and transthyretin amyloid clearing) and that are already on the menu of various start-ups.

Posted by: Barbara T. at April 9th, 2016 6:02 PM

@Barbara T.: de Grey's 25 year prediction has always been predicated on achieving significant funding, the estimated amount of which started at ~$100M/yr, and has been trending downward since then as the present low level of funding and progress elsewhere gnawed away a little at the scope of the problem. I'm surprised the conditional on funding point wasn't in this article, but maybe the editor dropped it.

Posted by: Reason at April 9th, 2016 6:14 PM

@Reason: To be honest I think that relying on a funding estimate made 15 years ago at a point in time when there are so many more players in the field should be reviewed. For example, the funds used to develop CRISPR Cas9 cannot be considered SENS-related and yet the technique advanced - or is going to - the cause greatly.

A more sophisticated estimate based on what is actually happening on the ground with both science and business would perhaps also sway some of the naysayers, since ballpark budgets and statistical models based on huge unknowns reflect neither discoveries that have the potential of sidestepping some of the most difficult SENS components (e.g. mature immunotherapy could be a stopgap measure until they figure out ALT), nor the contribution to the development of early therapies provided by private translational efforts.

Posted by: Barbara T. at April 9th, 2016 7:11 PM

@Barbara T.: Four years ago appears to be the last time I quoted any concrete numbers, but I'm sure they've show up in video presentations since then.

https://www.fightaging.org/archives/2012/04/aubrey-de-grey-on-the-costs-and-cost-effectiveness-of-sens/

I'm sure it couldn't hurt to go through the full planning exercise again, but equally I imagine that, like everything in this field, actually getting up and doing this suffers from the fact that the money needed would go a long way towards funding useful research. It is the same with outreach and education.

Posted by: Reason at April 9th, 2016 7:22 PM

Yeah, in those links he says the same thing as usual regarding the 25ish years given significant funding, etc. Not sure why MissK is patting herself on the back like she got one over on everyone here. There's literally nothing new in this article on that end. I think in an article on gigaoam or something like that, he said he could see RMR in 7-10 years from now though. I'll look for the link, though I'm sure Reason has posted the article already. I think it was towards the end of 2015.

Posted by: Ham at April 9th, 2016 8:11 PM

Correct me if I am wrong but if RMR is achieved in about 10 years, can bold life extentionists expect to have medical tourism clinics soon thereafter like Bioviva that have legitimate therapies? After all, aren't most biochemical processes in mice the same as in humans? Therefore human rejuvenation would have a good chance of success in an additional 10-15 years.

Posted by: Morpheus at April 9th, 2016 9:55 PM

It seems that Ray K said in the next decade that we would gain an extra year for each year that goes by. In other words, with medical tech increasing exponentially, if you are 70 years old, medical progress will be able to keep give you an extra year of living equal to each year you are alove. I hope all understand what I am trying to say.

Any comments or thoughts on this? I think this also align with the LEV theory.

Posted by: Robert Church at April 10th, 2016 12:59 AM

@Robert: That's exactly LEV, but AFAIK, Kurzweil thinks it will be achieved by nanotechnology, while AdG thinks it will be achieved by biomedicine. I think that nanotechnology is not so advanced yet. Biomedicine has the lead, by far.

Posted by: Antonio at April 10th, 2016 3:12 AM

My opinion is that we are well on the way in a number of areas such as gene therapy, stem cell therapies, tissue engineering and numerous other types regenerative medicine such as work with Telomeres. Progress depends on funding although a number of factors will drive things forward and interest is increasing among both Scientists and the general population as well as wealthy philanthropists. The greatest driving force of all is that the baby boomers are aging and this will place increasing demands on healthcare systems. Keep in mind that the average person costs more in medical expenditure in the last year of their life than all the other years put together. Also, the number of workers is declining in most developed countries which means that we need to keep the existing population working and productive as long as possible.

Of course there are numerous routes other than engineering approaches such as SENS and I think even Aubrey de Grey knows SENS is only a means to to get a foot on the ladder but clearly once SENS strategies are perfected they will certainly save millions of lives and prevent a great deal of suffering and I think they have the best short term chance of coming to fruition.

As I see it there are five technologies which will ultimately lead to radical life extension during the course of this century, these are advanced Biotechnology, Nanotechnology, Advanced Robotics, Genetics and mind uploading / whole brain emulation which I accept is a complex - but in all probability not impossible - route to life extension. Because all of these technologies exist currency other - than the last one - for life extensions technologies not to be developed in the next two or three decades requires that all these technologies must also fail to progress and I do not think based on current progress that is going to happen.

Posted by: John Anderson at April 10th, 2016 3:36 AM

''AdG: I still stand by both those statements, but please note that I always add the caveat that the former depends on adequate funding, especially in the coming decade. I define 'robust human rejuvenation' (RHR) as the addition of 30 years of extra healthy life to those who are already 60 when the therapies are first given. Longevity escape velocity is different - it's the postponement of aging faster than time is passing, which results from continued progress in improving the comprehensiveness of the therapies. The moment at which we reach LEV, which we call the Methuselarity (and we're pretty sure there will be inly one such moment, i.e. that once we exceed LEV we will never fall below it again), will probably occur at around the same time when we achieve RHR - maybe a little sooner, maybe a little later."''

His statement from 2012 is more clear about the intent and goals. I am surprised that he backtracked on his old paper (who said it took 25 years for first therapy, and 6 years wait for each subsequent therapy), he said that RHR (robust human rejuvenation) is

Robust ? What does he mean, How so/much in terms of years ?
'healthy 30 years extra' that's what he means, it seems.
Technically/in theory, RHR would allow partial rejuvenation depending on the amount of therapies that chime in and synergise (or not) together. If RHR is about 2 or 3 therapies out 7...it is a Robust 'health' effect, nothing to increase MLSP and certainly, not to escape lev.

As Michael Rae said, Reason, me and others, damage must be entirely wiped out to increase maximum lifespan - and thus, ESCAPE LEV, if these 7 therapies cover it all, then yes, maximum lifespan can be increased, LEV escaped and immortality possible. But if these therapies (whatever ones that have been created by that point) end up partial in effect, like a health effect rather than a true biorejuvenation - as in Reversal of Aging (DeAging, not just slow down, but total removal of damage), it Will Not make humans go above ~ 122 years old MLSP human specie lifespan very extreme limit standard.
It's impossible, damages will win over the SENS therapies, and MLSP will win again. SENS RHR will be a health effect, so if you are healthy, and your genes are good (family history/inherited centenarian longevity genes); SENS will only reduce whatever diseases that keep your potential to reach 100 or more.

The question that lingers, is what will RHR SENS do to already aged people who are 100, 110 super centenarians ? Are they game over too late ? We talked about this, damage is too high in them for salvaging, despite RHR. Aubrey de Grey said we have to do this in middle-life (his age, 53 years) to gain from RHR. RHR in 25 years, (for the 25 years old of today), will gave them that chance. Will a 75 year old AdG gain from RHR to get to LEV ? If AdG means that RHR is a 30 year health extension (that can be repeated ??), I don't see how RHR can make AdG go above 122 ever because he implies that RHR is using all
7 therapies or many of them; how then can this repair *all* damages and make any human overcome MLSP and reach LEV. I don't question to the greatness, it is a great thing, I just am curious (and worried) that it flops.

Anyway : D, just me talking/venting..his RHR is better than nothing at all. I really want to be optimistic, I just feel that it's more optimistic than what will turn out (don't like that feeling). I really want to believe more too. :)
Great input by all!

Posted by: CANanonymity at April 10th, 2016 10:49 AM

Back in 2001, Kurzweil predicted that immortality would arrive by 2011.

"With the revolutions in genomics, proteomics, rational drug design, therapeutic cloning of our own organs and tissues, and related developments in bio-information sciences, we will be adding more than a year every year within ten years."

http://www.kurzweilai.net/the-law-of-accelerating-returns

Posted by: Florin Clapa at April 10th, 2016 12:10 PM

Kurzweil was always full of it. That guy's business is book selling, not science.

Barbara, the only way Aubrey gets turned into an Alcorpsicle before he's 100, even with 2016 technology, is extreme bad luck or sudden violence (i.e. a car wreck). Trying to use generalized actuarial tables on a man whose business is LE is silly. (Hell, I'd estimate that regular readers of FA! have another decade or more of [assuming unextended] life than the average schmuck just because we know what kills us.) The man is not going to let himself catch the beetus and he's not going to readily let his brain's lymphatic system get clogged up. The reason he repeatedly says that things are speculative, uncertain, etc is because they are and he wants to make it clear to the world that he's not making ridiculous predictions (i.e. he's not Kurzweil).

But you are right in that a lot of other technologies are paving the way to life extension without being specifically labeled as LE, and you're also right that one of the seven targets (senescent cells) is getting hit. I wish the SENS Foundation would be a bit more loud about that and other progress, but then again I've wanted them to take credit for things for more than a year now...

Posted by: Slicer at April 10th, 2016 1:48 PM

I'm really good family friends with ana actuary (now retired). When I broached the subject of life extension with him last year his view was that it was interesting, but he'd believe cures for cancer and alzheimers when the data is there in the medical press. Actuaries just extrapolate the past. I don't think they'll bother to think about it at all until there is widespread news coverage of stories like "Enhanced CAR T cell immunotherapy achieves complete remissions in multiple solid cancers" or "GAIM therapy cures Alzheimers in most cases".

Posted by: Jiim at April 10th, 2016 4:44 PM

Speculation is pointless in my view. We are mere years from some regenerative medicine being practical eg, Senolytics, Stem cell therapy and GAIM to name three. The key thing now is to support the research to give us the best shot at making LEV.

Forget people like MissKaioshin and other naysayers, they are not in the lab, they do not see all that goes on so their opinion is nothing more than guesswork. You might as well use tea leaves or a crystal ball to try to anticipate when such things arrive.

"Guesswork is poor, logic is better but data is king" we do not need their permission to get this done so let us begin!

For the record I think Aubrey is conservative about the technology BUT I also appreciate he does not want to raise false hopes.So we will get the research done and we will see. The greatest barrier to progress is not the actual science it is regulation followed by funding.

The MMTP is in a unique position for the next two years in that we can do very low cost stem cell work to a high standard so we intend to capitalize on this. Keep your eye on lifespan.io we are about to launch!

Posted by: Steve Hill at April 11th, 2016 2:59 AM

Hey Steve H.

I appreciate your comments and especially what is near term regen medicine.
I am really appalled at some of the negative people. They totally ignore what is happening NOW in the field. This, IMO, includes AI (albeit soon), biotech, nanotech (also, soon), making better sense of the genome with big data (happening now), the immunology tech to fight cancer(I really thought Carter would be gone by now, especially at his age), and CRISPER gene therapy.

I feel quite confident that in the 30's we should have something of significance to keep us alive longer for at least a few more decades. Given the FDA issues, I am putting my money (literally) on medical tourism, though.

I really am very thankful for you, Steve, and others who have the right attitude to know anything is possible and are working at it. I only wish I was wealthy so I can make a significant contribution to the cause instead of lip service.

Posted by: Robert Church at April 11th, 2016 2:42 PM

People are misunderstanding me. I'm not just naysaying or trolling. What I'm saying is, it's odd that some people are so optimistic about SENS extending their lifespan and healthspan while Aubrey de Grey himself is so much more grounded in his expectations. People are saying that by the 2020s we'll have such-and-such treatments, by the 2030s we'll have such-and-such, and so on. But de Grey is saying that we'll be lucky to have even modest advancements by the 2040s.

Aubrey de Grey can of course be wrong, and maybe things will advance more quickly. But there has been some discouraging news recently. China tried to genetically alter more human embryos using CRISPR-Cas9, and the results weren't very good. It seems we're still a very long way away from using CRISPR on humans. And as for things like bioprinting, tissue engineering, stem cells, etc., many experts are very doubtful that these things are anywhere close to being clinically ready anytime soon. We can barely create human skin, and that's the simplest of all human tissues. We still can't control stem cells very reliably.

So that's why I'm so skeptical.

Posted by: MissKaioshin at April 11th, 2016 5:35 PM

CRISPR-Cas9 is not ready? Well Regeneron just bet up to $75 million on it being ready:

http://www.genengnews.com/gen-news-highlights/regeneron-intellia-partner-to-develop-crispr-cas-therapeutics/81252598/

"In return for its rights, Regeneron agreed to pay Intellia $75 million upfront, as well as pay undisclosed "significant" payments tied to achieving milestones, plus royalty payments on potential Regeneron products."

If you think you know something they don't know you could always short their stock.

Posted by: Jim at April 11th, 2016 6:05 PM

I have to think that at this point, everyone in the industry with a connection to past intellectual property that could be turned into a gene therapy, but which was not carried forward due to the costs and difficulties inherent in past gene therapy approaches, is now giving some thought to how to move forward with CRISPR, or how to license to someone who can.

Posted by: Reason at April 11th, 2016 6:19 PM

I can read :

"the only way Aubrey gets turned into an Alcorpsicle before he's 100, even with 2016 technology, is extreme bad luck or sudden violence (i.e. a car wreck). Trying to use generalized actuarial tables on a man whose business is LE is silly. (Hell, I'd estimate that regular readers of FA! have another decade or more of [assuming unextended] life than the average schmuck just because we know what kills us.) The man is not going to let himself catch the beetus and he's not going to readily let his brain's lymphatic system get clogged up"

OMG, I'm in That Weird Part of the Internet

Posted by: JimmyLord at April 11th, 2016 7:14 PM

@Misskaioshin,

If you are so convinced we are decades away from any significant improvements, why do you like to read the articles AND comments here?

Also, quoting China's failure with CRISPR is not surprising given their lack of QA and reputation of quality on many products. I would NEVER knowingly eat anything from China, btw.

Most of use on this site are optimistic and hopeful to make it to LEV. Although there is no guarantee, we have a number of reasons (as we mentioned above) to be hopeful. It seems you like to go against the crowd, for what reasons, I have no idea.

Posted by: Robert Church at April 11th, 2016 7:27 PM

Obvious troll is obvious...

"But de Grey is saying that we'll be lucky"

No, he says we have a 50% chance. That's not particularly lucky.

"to have even modest advancements by the 2040s."

No, he talks about rejuvenating 30 years people in their 60's. That's by no means modest.

Posted by: Antonio at April 12th, 2016 2:43 AM

Like I said trying to predict this is very hard. Lets just get the research going and follow the data! For every failure eg, china CRISPR there are many more successes and steps forward so we should of course avoid being over optimistic and lulled into complacency but in the same token we need to avoid being negative too.

MissKaioshin if you are not naysaying then you should be a bit more positive. Remember SENS is only one of many labs working on different and mutual approaches. Our researcher recently published some very promising stem cell data for example that shows reduction of plaque in AD pathology. So try and get with the program, we should be realistic but not pessimistic because just the same as over optimism this also encourages inaction.

Posted by: Steve Hill at April 12th, 2016 6:53 AM

To start with a direct quote of the passage that has raised most of the discussion:

De Grey readily admits that the likelihood of his research successfully extending his own lifetime is low. "I put it at 20-25 years from now when we have a 50-50 chance of getting to a decisive level of comprehensiveness that works, which I've called longevity escape velocity. If we do get there by then, I've got a fair chance of benefiting. But I have absolutely no doubt there's at least a 10% chance we won't get there for another 100 years because we hit new problems that we haven't thought of. So if I look at my own personal prospects, or the prospects of any other particular person, the timelines and uncertainty result in this all being very speculative."

Posted by: CANanonymity at April 9th, 2016 2:10 PM: "decisive level of comprehensiveness that works," I'm not sure what he means, but I'm guessing 'good enough', 'we understand our stuff enough' that we can make the rest of the therapies from now on.

As he indicates, this refers to the central thesis of actuarial escape velocity, which (as you seem to understand) means that we have achieved the first, decisive, comprehensive panel of rejuvenation biotechnologies: a panel that would, amongst them, effectively remove, repair, replace, or render harmless a sufficiently wide range of forms of cellular and molecular damage, and do so effectively and safely enough, to grant 20-30 years of additional life expectancy to a person in late middle age — which (to address one of your other confusions) is what he means by robust human rejuvenation (RHR).

This would mean that we can make the rest of the therapies from [then] on, in the sense that the quater century of increased life expectancy enjoyed by those first beneficiaries would be sufficient time to develop further refinements and additions to the panel, expanding its efficacy, safety, and comprehensiveness sufficiently well to increase life expectancies by a further 30%, which in turn would give them even more time alive — and, again, more time for medical science to deliver yet more and better rejuvenation biotechnologies. And so on, until we had aging under complete medical control, and life expectancy would be bounded only by causes unrelated to aging (violence, accidents, natural disasters, catastrophic infections, etc).

Posted by: CANanonymity at April 9th, 2016 2:10 PM: In 20-25 years, he and his SENS will not have All the 6 or 7 therapies made. If he implied that, he forgot his own longevity paper where he said the first therapy will take 25 years rough.

No, he did not: he said (as he repeats above) that with sufficient funding, we would have a 50-50 chance of having the first comprehensive panel of rejuvenation biotechnologies sufficient to achieve RHR. Such a panel would require not just one, nor even seven individual rejuvenation biotechnologies (since there are several key aging lesions that will need to be repaired to achieve RHR even within the seven categories of cellular and molecular damage of aging), but a dozen or more.

Posted by: CANanonymity at April 9th, 2016 2:10 PM: And then it will be quicker/easier/more experienced for new ones..so a 6 years wait for each other new therapy. Totaling more than 50 years. I think he meant just for the first one that's it, to have some kind of 'direction/momentum' to create the 6 others.

The paper that you're misremembering models what happens after the first, comprehensive panel of rejuvenation biotechnologies is achieved. The model is premised on further iterations of rejuvenation biotechnologies cutting by half the impact of each category of aging damage on health and functionality every six years. It would then take 42 years to complete such a cycle for all seven categories of aging damage.

At the other end:

CANanonymity at April 10th, 2016 10:49 AM: As Michael Rae said, Reason, me and others, damage must be entirely wiped out to increase maximum lifespan

Here you are falling into a similar error at the other end of the process. If damage must be entirely wiped out to increase maximum lifespan, there would be no point in iterating further improvements on or additions to the first achievement of RHR. Rather, as I said in the post you're misremembering (at February 3rd, 2016 4:46 PM), "To move the needle on maximum lifespan, you have to push back on all of the cellular and molecular damage of aging, not just one form." That is, in order to achieve RHR (and initiate LEV), the panel of rejuvenation biotechnologies must be comprehensive, removing or repairing substantial amounts of all of the categories of aging damage, inclusive of the specific instances within each category that actually limit the current "normal" lifespan.

But you don't have to "wipe out" all such damage to proportionately extend the maximum potential life that a given person can live. Remember, even newborn infants have some level of aging damage in their tissues, but they still have many decades of life ahead of them, because in no tissue is has the burden of aging damage reached a "threshold of pathology" at which diseases of aging emerge and life becomes threatened. Thus, the goal is only to remove or repair sufficient amounts of each cellular or molecular lesion in the tissues to restore tissue integrity to levels equivalent of a person sufficiently younger, who has a given amount of potential lifespan ahead of him or her, to give that same potential to the recipient of the therapies.

The reciprocal of this, of course (and what you had misremembered or misunderstood), is that you can't push back on just one or just a few forms of aging damage and expect an increase in maximum potential lifespan for any individual, because of the "weakest link in the chain" problem: other forms of aging damage will continue to rise to pathological levels on more or less their original trajectory, even as the one(s) that you have reduced are pushed further away from that threshold. There is somewhat of an analogy here to genetic disorders that cause greatly-accelerated accumulation of the remaining forms of aging damage, such as the mutations in APP or PS1 that cause familial, early-onset Alzheimer's disease, or those in Parkin or PINK1 that cause young-onset Parkinson's (but in all of the remaining forms of damage instead of just one): the person is young in many respects, but on a severe trajectory toward morbidity and mortality because of a high burden of a subset of "normal" aging damage.

The goal, brief, requires comprehensive reductions in the burden of aging damage, leaving a person with the structural integrity of a much chronologically younger person who still has many decades ahead of him or her — not that the burden of all aging damage has to be "wiped out" (brought down to zero).

Posted by: CANanonymity at April 10th, 2016 10:49 AM: The question that lingers, is what will RHR SENS do to already aged people who are 100, 110 super centenarians ? Are they game over too late ? We talked about this, damage is too high in them for salvaging, despite RHR. Aubrey de Grey said we have to do this in middle-life (his age, 53 years) to gain from RHR. RHR in 25 years, (for the 25 years old of today), will gave them that chance. Will a 75 year old AdG gain from RHR to get to LEV ? If AdG means that RHR is a 30 year health extension (that can be repeated ??), I don't see how RHR can make AdG go above 122 ever because he implies that RHR is using all 7 therapies or many of them; how then can this repair *all* damages and make any human overcome MLSP and reach LEV. I don't question to the greatness, it is a great thing, I just am curious (and worried) that it flops.

You're certainly right that as a person suffers with increasing burdens of aging damage, our ability to rejuvenate them effectively and safely declines, eventually reaching a null or negative point, and that this plays into Dr. de Grey's assessments of his own odds of reaping the full benefits of rejuvenation therapies himself. This is itself modeled in the paper you've misrecalled or misunderstood (Figure 5), so this is not a question that still "lingers" in the sense that no one has thought of or addressed it, or to which no one has an answer beyond idle speculation. When inspecting the graph, note again that the ages given are ages for receiving the first comprehensive panel of rejuvenation biotechnologies with ongoing iterative improvements, not the age that the first individual "damage-repair" therapeutic arrives; and that the y-axis is the proportion of the original cohort of a given age at receipt of first full treatment still alive by a specific age, so that once a given survival trajectory reaches its plateau, all or very nearly all of the remaining members of the original cohort survive until killed by something other than aging.

Posted by: CANanonymity at April 9th, 2016 2:10 PM: "...which I've called longevity escape velocity." It's good he remembers (of course : D...he wrote it), but he is standing by his research paper. Although, I clearly 'Sens'e (pun intended, had to : D, that he is trying to not make extreme outlandish claims, because he knows his longevity escape velocity paper would allow immortality by rejuvenation; which does not sit well with people (like the fatalists) who don't believe in rejuvenation, as we wish, that could allow eternal life. And he knows that everyone knows his SENS therapies could allow that, so he doesn't want to give false hopes if it fails to even rejuvenation all that much.

Dr. de Grey has never, ever backed away from the actuarial implications of the "damage-repair" heuristic of SENS: such is, indeed, the whole basis of the talk he gave that sparked this discussion. On the other hand, neither the escape velocity paper, nor the mathematical model of the progress of rejuvenation biotechnologies, nor anything else he has said asserts or implies that rejuvenation biotechnology will allow immortality by rejuvenation or allow eternal life. It would "only" dramatically extend life expectancy by eliminating age-related causes of ill-health and death.

MissKaioshin at April 9th, 2016 4:54 PM: This is significant because Aubrey de Grey himself is admitting that our chances are extremely slim. I've said before that none of us are going see longevity escape velocity in our lifetimes,

It is a mischaracterization of Dr. de Grey's views to say that he "is admitting that our chances are extremely slim." The author of the press story summarizes Dr. de Grey's assessment of his own prospects as given above based on the timeline that the journalist translates as indicating an "extremely slim" chance for Dr. de Grey. Whether "a 50-50 chance" of achieving robust human rejuvenation within 25 years, intersecting with the current lack of the funding, or the trajectories laid out in the paper and results graph discussed above, should be characterized as "extremely slim" chances for Dr. de Grey or for any individual is a qualitative and necessarily somewhat subjective judgement.

To be meaningful, such characterization needs to be informed by a given person's current age and health and risk factors, and will ultimately depend on how quickly we will collectively succeed — through philanthropic giving, advocacy, and political action — in initiating the necessary radical reorientation of global biomedical research: away from the current approach of modulating aberrancies of metabolism and "managging" metabolic risk factors, and toward the "damage-repair" model necessary for the comprehensive prevention and reversal of the diseases of aging. Simply on their face, the journalist's gloss is on the pessimistic side, though perhaps not as outrageous as Barbara T or Slicer's initial take on the matter.

Posted by: Barbara T. at April 9th, 2016 6:02 PM: This [timescale] flies in the face of a number of very important scientific discoveries ... as well as the existence of therapies for which there is proof of concept (e.g. senescent cell and transthyretin amyloid clearing) and that are already on the menu of various start-ups.

... and similar comments by John Anderson. This is all very good work; I might also highlight the even more advanced state of development of immunotherapies targeting the removal of beta-amyloid, alpha-synuclein, and malformed tau, all of which are now in human clinical trials, as well as ongoing support for cell therapy. However, we have to remember the "weakest link in the chain" problem, as discussed with regard to the similar case of clearance of large numbers of senescent cells: to achieve RHR will require successful targeting of each and every one of the various cellular and molecular aging lesions that currently contribute significantly to limiting human life expectancy due to aging. There is currently good investment in a minority of areas of rejuvenation research, and happily a few startups going after some of the less well-supported ones, but even those lean more toward targets that are perceived to be low-hanging fruit: one high priority for SENS Research Foundation is therefore to use critical-path analysis to invest our very limited resources in areas that are as yet being neglected by such players.

I would note that you list amongst your examples ongoing progress on true clearance of wild-type transthyretin amyloid. This is itself work funded by the Foundation.

Posted by: Barbara T. at April 9th, 2016 6:02 PM and 7:11 PM: This [timescale] flies in the face of a number of very important scientific discoveries such as CRISPR Cas9 (in 2003 de Grey himself said that the fact that gene therapy was "still rather black magic" was a major obstacle to the implementation of SENS)  ... [T]he funds used to develop CRISPR Cas9 cannot be considered SENS-related and yet the technique advanced - or is going to - the cause greatly.

I think you're thinking about this somewhat backwards. The budget was intended to include only core work on rejuvenation biotechnology: it assumed the ongoing progress in life sciences generally, including above all things like gene therapy, which is a robustly-supported area of research whose medical value is very widely accepted in biomedical research and only modestly controversial in public discourse. The original timescales therefore essentially assumed the emergence of robust gene therapy and other tools of widespread biomedical utility out of general biomedical research — and remember that it was made at a time when the NIH budget "doubling" (so-called) was still ongoing and expected to continue, rather than suddenly being flatlined or declining in the face of inflation beginning in the middle of the previous administration. And even very robust gene therapy is an enabling tool for delivering rejuvenation biotechnology, rather than itself one of the key therapies that needs to be developed.

As to the CRISPR/Cas9 system specifically: this is certainly a very useful tool for biomedical research, with utility for delivery of some SENS therapies as well — notably, editing stem cells to enable some therapeutics (and to make them impregnable to cancer), because those can be modified ex vivo, and defective cells can be screened and discarded, while successful transfectants can be expanded and seeded back into the tissue.

This kind of approach can also be used for nearer-term medical applications not directly related to rejuvenation goals as such: for instance, the Regeneron/Intellia agreement highlighted by Jim, involving ex vivo manipulation of haematopoietic cells for CAR-T cell therapy and other haematopoietic applications, as well as for liver cells in people receiving a liver transplant as part of treatment for hereditary transthyretin amyloidosis resulting from an aggregation-prone mutant transthyretin gene (a quite different problem from dealing with senile systemic amyloidosis, where the normal, wild-type protein aggregates due to stochastic damage).

But your (Barbara's) implicit premise seems to be that the CRISPR/Cas9 system could easily be used for somatic gene therapy — ie, introducing therapeutic genes into existing tissue in situ. And if you didn't mean that, such is certainly the explicit premise of others in the comments to this thread, and in previous comments in FA! to which I've not previously responded. In fact, using the CRISPR/Cas9 system for this purpose would require a great deal of innovation, including the emergence of strategies that no one has yet identified, even in principle.

For one thing, CRISPR/Cas9 does not come with any kind of vector system to deliver both components of it, and we don't have a sufficiently safe and effective delivery vector for it, although people are certainly working on delivery systems all the time. And whereas most delivery systems for gene therapy currently in use are for a single active component, it's actually at the moment very difficult even in cell culture to assure the coincident presence (and expression, as relevant), in the same cell at once, of all of the components of the system (the Cas9 exonuclease, the guide RNA, and the exogenous repair template) — let alone to do this in vivo across an entire somatic tissue. Additionally, the payload size that the system can handle is as of yet far too limited to be used for any kind of gene therapy useful to us, although people are working on that, too.

There are much larger problems, however, that are more central to the genome-editing mechanism of the system itself. The system works because the Cas9 endonuclease makes double-strand breaks in the host cell genome (or, using the trickier, engineered "dual nickase" system, you use two modified Cas9s that each make its own single-strand breaks at one end of the desired insertion site) at a site determined by the guide RNA, and the cell's DNA repair machinery "repairs" the break with new genetic material introduced in a separate repair template. The cell can use one of two DNA repair mechanisms to do this: the Non-Homologous End Joining (NHEJ) pathway or the Homology Directed Repair (HDR) pathway.

NHEJ is more or less OK for making decent-sized loss-of-function mutations (which scientists often want to do), but is too sloppy to be used for insertion of therapeutic genes, whether in mice or in humans: it often leaves small insertions or deletions that bridge over the site of the break in the strand, resulting in either frameshift mutations or premature stop codons within the open reading frame of the gene, resulting in either a protein that is prematurely truncated and useless or producing useless mRNA that just gets degraded by nonsense-mediated decay (or, theoretically, even a gene with a deleterious gain-of-function mutation, though I've never heard this raised as a serious prospect).

HDR is very precise, but it has a very low (<10% of modified alleles) efficiency, and it is only active in cells that are actively in the process of dividing, making it useless for introducing therapeutic genes into mature neurons or heart and skeletal muscle cells, and for substantial numbers of cells in organs like the liver and the skin at any given time.

Robert Church at April 11th, 2016 2:42 PM: [Pessimists] totally ignore what is happening NOW in the field. This, IMO, includes AI (albeit soon), biotech, nanotech (also, soon), making better sense of the genome with big data (happening now), the immunology tech to fight cancer(I really thought Carter would be gone by now, especially at his age), and CRISPER gene therapy.

It's quite a differnt thing, you must agree, to revise forecasts based on actual technological developments that occur in the period between when a projection is made and a future interim period, and to do so based on developments that are still undeveloped but anticipated. And for what it's worth, I don't think any of these cases should be used for either purpose. While "big data" on genomics is useful for optimizing the use of conventional medical therapy, it really doesn't do anything for either development or application of rejuvenation biotechnology — except inasmuch as it might help to optimize individual patients' regimen of rejuvenation treatments after we have enough patients already being treated for enough years to get longer-term health trajectories out of them, and also have the diagnostic assays needed to acquire such data in the first place and then use them to guide the treatment of patients. Nanotechnology of the sort that would be useful to develop rejuvenation biotechnology (ie, Drexlerian atomically precise manufacturing devices that can be used in situ in the aging body) is still many decades off into the future, with a few exceptions involving much simpler tech like advanced nanomaterials for use in scaffolding for tissue engineering: it is likely to play a key role in future iterations of the "damage-repair" heristic, but is unlikely to play any role in the first. And see above on the CRISPR/Cas9 system.

Posted by: Barbara T. at April 9th, 2016 6:02 PM: I wish that de Grey revised his forecast downwards since he has been saying that aging will be under decisive control in 25 years for at least a decade.

Dr. de Grey has on occasion in general terms speculated on how much recent advances have shortened the remaining timeline, granted that we remain far short of the needed targeted funding of rejuvenation biotechnology: Antonio has already linked two examples, and I will add a third, more detailed one:

Are Aubrey de Grey's estimations for the advent of SENS changing over the time he makes them?[Q:] In 5 years since creation of the SENS Foundation, dit the years-from- now estimation for "longevity escape velocity" shorten?[A] Aubrey de Grey, Biomedical gerontologist, Chief Science Officer of SENS Foundation:... It's been about ten years since I started making predictions ... I think we're about three years closer to [robust mouse rejuvenation]; in other words we've slipped by about seven years. We've probably slipped by only a couple of years for RHR ... [T]he only area in which I was overoptimistic was with regard to the ease of securing adequate funding: I think I would indeed have predicted that the funding we've actually had would have resulted in progress being about three times slower, which indeed it has been. The conclusion is clear: the world is spurning the opportunity to make a really big difference to how soon we bring aging under medical control and to save a vast number of lives, probably in the hundreds of millions.

Indeed. The vast majority of biomedical research dollars — from venture capital, Big Pharma, charitable, and the all-important public health research institutes of the advanced economies (NIH, CIHR, MRC, Australia's NHMRC, etc) — are still being ploughed overwhelmingly into the old metabolic "risk-factor" model. The advent of RHR will remain a moving target until that fundamentally changes.

Posted by: Michael at April 15th, 2016 12:58 PM

"It's been about ten years since I started making predictions ... I think we're about three years closer to [robust mouse rejuvenation]; in other words we've slipped by about seven years. We've probably slipped by only a couple of years for RHR".

But if I understand this correctly, the above sentence means that he predicts the first comprehensive panel of therapies (RHR) to be only 17-18 years away (thus 15-20 ballpark) rather than 20-25. This because slipping by "only a couple of years" results in: 25 years (original prediction) - 10 years (time from original prediction) + 2-3 ("couple of years" slippage). So why is RHR still "20-25 years from now"?

Also, it could be that I am splitting hairs, but I feel that from an 'emotional' perspective having that number 25 still in the prediction a decade down the line can make people 'feel' that the there has been zero progress, and thus the whole enterprise is not worth bothering with since at this pace it may take centuries for it to bear fruit.

It's not admitting a slower than expected pace of progress due to lack of adequate funding that I see as an issue, rather the discouragement that the potential zero progress implied in that "25 years away" still in the prediction generates. And people who don't believe in a project are not going to fund it...

Posted by: Barbara T. at April 16th, 2016 7:49 AM

I'm going to try to clear up the confusion about Aubrey's predictions. Aubrey's original prediction was that there's a 50% chance that RMR is 10 years away and another 15 years for RHR if SENS research gets $100 million per year for 10 years (to get to RMR). Given the overall low level of funding that SENS has received to date, only 3 years of progress has been made toward RMR. So, 7 years are still needed to get to RMR (with RHR coming about 15 years after RMR) but ONLY IF SENS gets funded by that $100 million per year he mentioned in his original prediction (by now, it would be for only 7 years for a total of $700 million). If SENS gets substantially less than the $100 million per year (like it's getting today), RMR will arrive in 12-15 years and RHR in 30-35 years. If that's still a bit confusing, a breakdown of both funding scenarios might help clear things up:

High funding level
RMR: 7 years away, 2023
RHR: 20-25 years away, 2036-2041

Low funding level
RMR: 12-15 years away, 2028-2031
RHR: 30-35 years away, 2046-2051

https://www.reddit.com/r/Futurology/comments/3xrr9u/were_aubrey_de_greys_predictions_from_2005_too/cy7o2ds

Posted by: Florin Clapa at April 16th, 2016 1:40 PM

This goes to show how people can interpret things differently. To me - especially reading the original article and specifically the following passage -

"I think we're about three years closer to RMR, in other words we've slipped by about seven years. We've probably slipped by only a couple of years for RHR, BECAUSE THE FACT THAT THE TRANSLATION OF RMR TO RHR WILL BE HAPPENING LATER MEANS THAT IT WILL BE ABLE TO TAKE GREATER SERENDIPITOUS ADVANTAGE OF DISCOVERIES MADE FOR OTHER REASONS"

https://www.quora.com/Are-Aubrey-de-Greys-estimations-for-the-advent-of-SENS-changing-over-the-time-he-makes-them

this means that while RMR will arrive 7 years later than expected (so 2005+10+7 years=2022), RHR will arrive only 2 or 3 years later than originally predicted (so 2005+25+2=2032).

This is different from what you are saying but I think it's what being "able to take greater serendipitous advantage" means. I think that because the efforts to rejuvenate a mouse proceed in parallel with the efforts to rejuvenate humans (even though these are not explicitly marketed as rejuvenation), the life-cycles of RMR and RHR do not necessarily move at a constant and simultaneous speed.

Of course this whole discussion is still completely speculative and arguing about exact years is likely senseless, but the point I am trying to make is that it seems that Aubrey's prediction is still pointing at the same end-date (25 years from now) rather than showing progress.

Posted by: Barbara T. at April 16th, 2016 2:14 PM

Barbara T., you're misunderstanding what Aubrey is saying, because you're ignoring his funding qualifier (e.g., "....so long as funding of all the relevant research was adequate."), and apparently, even his Reddit comment. The 7-year slip is due to the low funding situation, not due to any arbitrary change in his prediction. If SENS had adequate funding beginning in the year Aubrey first made his prediction, RMR should have been achieved by now. Since SENS has NOT received adequate funding, it has made only 3 years of progress toward RMR (out of the 10-year total needed for RMR). It's made that much progress even without getting $100 million per year, because it's been easier to make progress as time passes due to improvements in technology. The "surreptitious advantage of discoveries" like CRISPR also serves to speed progress even in the absence of adequate funding. However, improvements in technology and surreptitious discoveries can't replace that $100 million per year in funding. That's why Aubrey mentions in his Reddit comment two funding scenarios (which I've clearly outlined in my earlier comment) with substantially different timeframes.

Posted by: Florin Clapa at April 16th, 2016 6:19 PM

No Florin, you are missing my point completely. Funding or not funding what the article quoted by Micheal says is that while we are lagging 7 years behind with RMR, we are "only" lagging 2 years behind with RHR because of the "serendipitous" (rather than surreptitious as you say) "advantage" deriving from the fact that the two efforts do not take place 100% consecutively.

This is independent of funding, or better it assumes money flowing as planned. But the funding situation is not the issue here: what I am saying is that at one point Aubrey seems to give us a 17-18 year timeline (the "slipping ONLY a couple of years" [re: RHR] part), and at another he suggests that we are still 20-25 years away from RHR. This is what those quotes say as they are presented to us. Again, since the two interviews were given only a few months apart during the past year, I can't imagine that the discrepancy, which is what I am trying to understand here, was caused by de Grey having two very different opinions of the current funding climate.

On the point of funding, I would also like to point out the fact that the costs of setting up and running a lab have gone down greatly in recent years and probably in ways that no one could predict with any accuracy a decade ago, so even the funding forecast itself should likely be reviewed.

Posted by: Barbara T. at April 16th, 2016 6:50 PM

In fact, your quoting of yet another article with yet another prediction (30-35 years for RHR with "weak" funding") just highlights the unreliability of modelling timelines using great differences in funding, since results can vary to the point of becoming meaningless depending on the numbers you throw in. My point is that with "strong" funding, which is what is assumed in both the Quora interview quoted by Michael and the original FA post, we still have two jarring 2015 predictions.

What I think would be useful from an advocacy / communication point of view is if all predictions: 1) Assumed that the level of funding is optimal (what people want to know is how long it will take for science to get there in principle - if science can do it people will pay all that it takes); 2) Got rid of that "25 years away" as it smacks of zero progress; 3) Refrained from varying too much between each other because inconsistency may bring people to question their validity.

Posted by: Barbara T. at April 16th, 2016 7:27 PM

Aubrey claims that the best case scenario for the RHR timeframe is a range of 20-25 years from the present. 7 years (for RMR) + 13 years (for RHR) = 20 years. That's 2 years less for RHR compared to his original prediction, and this matches his Quora comment. The max timeframe should probably be 22 years (7 years for RMR + 15 years for RHR) rather than 25 years, since any timeframe that's more than 22 years would mean more than 15 years for RHR. Anyway, I suspect he's using a 20-25 year timeframe because it's more memorable than 20-22 years. He might also have realized that he could be wrong about the slight reduction to RHR's timeframe, since the timeframe for RHR is probably more speculative than RMR.

FWIW, I've heard Aubrey mention that SENS might get away with $50 million per year but that $100 million was a safer bet.

Yeah, I can see how all of this can get confusing, but I doubt anyone other than life extension nerds like us care one way or another about the specific timeframes. I like them, because it gives a certain amount of hope even if funding will continue to be a problem. It can also provide a rationale for helping out. Let me put it this way: if timeframes for SENS were perceived to be too speculative to consider, SENS funding would likely be less, possibly much less.

A case can be made that the entire way SENS is portrayed and marketed is problematic, but I'd rather not get into that here.

Yes, it should be "surreptitious" rather than "serendipitous."

Posted by: Florin Clapa at April 16th, 2016 9:53 PM

"Serendipitous" rather than "surreptitious," to correct my correction.

Posted by: Florin Clapa at April 16th, 2016 9:56 PM

I agree with Barbara, the two quotes are contradictory. Anyway, let's do all we can, regarding funding and advocacy.

Posted by: Antonio at April 17th, 2016 2:13 AM

Am I being extreme with my prediction, Michael? I may be. I strongly hold that people accelerate their own damage processes through bad lifestyle choices, and the average life expectancy is heavily influenced by this (even more than what shows on generalized actuarial data). "Do you actually know what you're doing in regards to extending your life" isn't something that actuaries can reasonably ask.

It's based on an impossible presumption (that nothing will happen in the next X decades), anyway.

"A case can be made that the entire way SENS is portrayed and marketed is problematic, but I'd rather not get into that here."

Well, Florin, we need to get into it somewhere, because it's the problem with this organization. The focus on neglected projects makes sense from a broad scientific perspective, because someone's gotta do it, but unless those projects are going to yield relatively near-term results (i.e. a glucosepane breaker in human clinical trials), the SRF's funding is always going to remain low. People aren't going to believe in the damage-repair model unless some damage, any damage, gets repaired; people aren't going to go "this is a successful organization" until the SRF can take credit for it and close the credibility gap.

But we've been over this. Publish or perish. Results or forget it. Take the credit or nobody cares who you are or what you represent. If I were in de Grey's shoes I'd be going "I talked a while ago about senescent cells; here's how these companies are working on removing them" instead of giving variants of The Usual Interview (you've read one Aubrey interview, you've read 'em all). Take a page from Donald Trump's playbook when it comes to advocacy (loud, proud, and not caring about detractors).

Right now, Googling "SENS senolytics" has the top two results from this website. That shouldn't be.

Posted by: Slicer at April 17th, 2016 1:37 PM

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