31 replies to this topic

[brokenportal]

Could somebody direct me to, or tell me if there are any alternate lists of things to be done other than the SENS 7 deadly things? You know, like, are there any other people who think that there is a list of other things rather than those?

[brokenportal]

And or, what are the main basic things that people say in opposition to sens?

[Mark Hamalainen]

Check out Prometheus vs SENS in the biotech forum for scientific critiques of SENS.

[reason]

Supposedly, the ire of Pontin will manifest itself in some sort of addressal of SENS by Cynthia Kenyon later this year:

http://www.fightagin...ives/000487.php

Reason
Founder, Longevity Meme
reason@longevitymeme.org
http://www.longevitymeme.org

[ag24]

Prometheus wrote:

> One of the biggest problems with SENS obtaining scientific credibility traction has been the
> persistent absence of on-the-record criticism from the biogerontology community.

I would go a lot further -- I would say that this is by a long way the #1 biggest problem.

> I personally find it frustrating that scientists are so reserved about their opinions and one
> cannot but help concluding that either they view SENS as baloney or they are decidedly
> unsure.

The main reason is not quite either of those -- it's that they are well aware that they would have to do a lot of reading of aspects of biology that are not classed as gerontology, and to which they are thus not normally exposed, in order to form an educated opinion on SENS. (Namely, not just my own publications but also quite a few of the data papers that I cite.) Their choice is thus to say publicly that they don't know (which is not something that most scientists, especially high-profile ones, find easy to do), to say publicly that I'm wrong but risk their ignorance of SENS being shown up by my responses (which is something that commentators like Olshansky, Sprott or Hayflick are unconcerned about but working biogerontologists are very reluctant to risk), or to say nothing. Or, of course, to actually as such do the reading in question (or just talk to me more about SENS) -- but that takes time, and all scientists are very busy, so there is a catch-22: they have to be convinced in advance that SENS has a case to answer. I am frankly in awe of Pontin that he succeeded in enticing Cynthia to write this critique. (Well, I guess we shouldn't count our chickens quite yet.)

> In effect, SENS as a whole has thus not directly been subject to peer review

Well, as someone pointed out recently, there are one or two semi-exceptions to this: in particular ANYAS 959:452 was de facto peer-reviewd by virtue of its co-authors' agreement to be co-authors. But the essence of your comment is absolutely correct.

[Michael]

All:

Prometheus: One of the biggest problems with SENS obtaining scientific credibility traction has been the persistent absence of on-the-record criticism from the biogerontology community.

ag24: would go a lot further -- I would say that this is by a long way the #1 biggest problem.

I'm surprised that you would put it as the biggest problem, especially at this early stage. Whether or not there is ever any genuinely cogent critique of SENS in the biogerontology community, I expect that the perception of the public -- on whom the initiation of the "War on Aging" depends -- will be the same: either hope, or pie-in-the-sky pessimism, until at least "robust mouse rejuvenation." Few amongst the general public will ever be aware of the existence of such a critique, or for that matter of its current nonexistence. They get sound bites, and journalists will ALWAYS get negative soundbytes -- hwoever knee-jerkish -- for "balance" (cf the constant citation of non-climatologist critics of an anthropogenic role in global climate change).

Prometheus: I personally find it frustrating that scientists are so reserved about their opinions and one cannot but help concluding that either they view SENS as baloney or they are decidedly unsure.

ag24: The main reason is not quite either of those -- it's that they are well aware that they would have to do a lot of reading of aspects of biology that are not classed as gerontology, and to which they are thus not normally exposed, in order to form an educated opinion on SENS.

Is not knee-jerk reaction to the sheer audaciousness of the stated goal -- let alone timetable! -- more likely to lie behind this than mere laziness?

ag24: I am frankly in awe of Pontin that he succeeded in enticing Cynthia [Kenyon] to write this critique. (Well, I guess we shouldn't count our chickens quite yet.)

Alas, as we now know, Kenyon has reneged on her commitment to critique de Grey's SENS platform.

Prometheus: I applaud his effort to seek a more suitably qualified person, particularly a highly respected and progressive molecular biologist like Kenyon ... (of course he could have pulled out all stops and not only included Kenyon but Guarente,

As a naked ad hominem it should be noted that Kenyon and Guarente are pursuing exactly the kind of preventive, messing-with-metabolism approach that Aubrey has openly and repeatedly criticised as futile (eg (1,2)), so they may not be the most unbiased critics.

Prometheus: I applaud his effort to seek a more suitably qualified person ... he could have pulled out all stops and ... included  ...  Hayflick

Hayflick is such a rabid, fanatical antagonist to both the feasibility (he has flatly stated that "No intervention will slow, stop, or reverse the aging process in humans" and advanced a completely fallacious argument to conclude that "intervention in the aging process borders on the likelihood of violating fundamental laws of physics”, rendering “being ‘anti-aging’ comparable to being ‘anti-gravity’ or oppose[d to] other fundamental laws of physics and chemistry”(3) -- see my in-press rebuttal (4) when the Journals finally catch up) and the desirability (!) of intervention in aging; I dont' think that we can expect any reasoned analysis of SENS from this expired oracle.

Prometheus: [Ditto for] Campisi

Yes, I'd very much like to see Campisi's views in writing. On the one hand there is her signing-on to the original manifesto for the SENS anti-aging platform:

We survey the major categories of such damage and the ways in which, with current or foreseeable biotechnology, they could be reversed. Such ways exist in all cases, implying that indefinite postponement of aging--which we term "engineered negligible senescence" --may be within sight.(5)

On the other hand, we have her statement in Popular Science:

Campisi: Aubrey will say something that’s the biological equivalent of 'Let’s build a 1,000-story building on the head of a pin, and then we can—,' and I’m like, 'Wait, wait, let’s go back to that first part again'” ... On the other hand, though Campisi has yet to feel compelled to do an experiment because of a conversation with de Grey, she doesn’t rule it out. “I wouldn’t waste my time talking to him if I thought it would never happen”

I am informed from a reliable source that the first of the Popsci quotes is somewhat out of context and makes her sound overly pessimistic, but I would still like to see a reasonably detailed exposition of her views, particularly after the further development of the SENS platform in the last few years.

-Michael

1: de Grey AD.
The unfortunate influence of the weather on the rate of ageing: why human caloric restriction or its emulation may only extend life expectancy by 2-3 years.
Gerontology. 2005 Mar-Apr;51(2):73-82.
PMID: 15711074 [PubMed - in process]

2. de Grey AD.
Book review: Ageless Quest
Bioessays. 2004 Jan;26(1):108-9
http://www3.intersci...571865/ABSTRACT

3. Hayflick L.
"Anti-aging" is an oxymoron.
J Gerontol A Biol Sci Med Sci. 2004 Jun;59(6):B573-8.
PMID: 15215267 [PubMed - indexed for MEDLINE]

4. Rae MJ.
Anti-Aging Medicine: Fallacies, Realities, and Imperatives.
J Gerontol A Biol Sci Med Sci. 2005; in press.

(See also:
Rae MJ.
All hype, no hope? Excessive pessimism in the "anti-aging medicine" special sections.
J Gerontol A Biol Sci Med Sci. 2005 Feb;60(2):139-40.
PMID: 15814852 [PubMed - in process]

5. de Grey AD, Ames BN, Andersen JK, Bartke A, Campisi J, Heward CB, McCarter RJ, Stock G.
Time to talk SENS: critiquing the immutability of human aging.
Ann N Y Acad Sci. 2002 Apr;959:452-62; discussion 463-5.
PMID: 11976218 [PubMed - indexed for MEDLINE]
http://www.gen.cam.a...sens/manu12.pdf

[John Schloendorn]

Hm, sounds dangerous. Paying someone to endorse something is not quite a testimony to the impartiality of the endorsement. I could think of a few deathists who would love to point this out in public.

[John Schloendorn]

I agree, it would be much better than no critique at all.

[ag24]

Plenty of thought is currently going into this. An idea that Dave G originally raised is gaining momentum: it involves offering a substantial financial incentive for such a critique. There are definite technical hurdles in designing this so that the money can't be won by something that looks rigorous but is in fact full of holes the size of Canada that I have already addressed in detail in print, but we think we can avoid that. But that means that the likely outcome is the continuation of the current situation that no such critique actually appears. The logic is that the absence of such a critique at the moment can be explained by the mainstream with "Aubrey's ideas are so daft that it's not even worth my time to explain why they are", whereas if there is serious money available then the mainstream scientist will have a much harder job convincing a journalist (or a potential philanthropist) that that's really why they're not writing such a critique. But I would like the views of those here: is that the situation we should be creating, or should we be encouraging the writing of (inevitably hole-ridden) critiques that can then be appropriately rebutted? (I of course omit the scenario that someone writes a critique that is genuinely cogent -- if that happens, we're in an altogether different world and I'll cross that bridge when I come to it.)

[caliban]

Prometheus: In any case, a well researched critique will itself have to withstand the scrutiny of peers and any indication of bias would be rather obvious, I would think.

Hope you don't mind if I am rather frank Aubrey:

By now, most aging researchers I talk to (thats usually postdocs and tenureds, but not the REALLY big names) have heard of you, but few have heard of SENS.

And at that level its all about pettyness: Bearded engineer, never done any research, says we can live forever.

So if a critique comes about those people will say
"Hah, finally that nerd got told by (Hayflick)"

without even reading it. And any rebuttal will be seen as a sorry struggle.

Now maybe those people are not the audience but the wider public. Then you are running the risk of confusing them with a very scientific discussion.

Thats not to say the incentive plan is flawed. It would be nice to get a good critique if only to test the ground. And if you manage it carefully, it might even communicate and help to raise profile.
But it might not be the big breakthrough.

[John Schloendorn]

if there is serious money available then the mainstream scientist will have a much harder job convincing a journalist (or a potential philanthropist) that that's really why they're not writing such a critique. But I would like the views of those here: is that the situation we should be creating, or should we be encouraging the writing of (inevitably hole-ridden) critiques that can then be appropriately rebutted?

Either is a step forward. Which happens should depend on whether the Dave's $5k is enough to actually attract someone. I'd prefer if it did. I'd rather have people and the media talk about SENS than not. People get convinced easier if they hear about a thing often, and from different sources. Every rebuttal and counter-rebuttal serves that end.

[ag24]

John - right re the $5k, and we are thinking about upping the ante considerably. Re repetition from multiple sources - also right, but of course rebuttals and counter-rebuttals are not the only ways to get that to happen.

Caliban - right too, and this is largely why we are thinking about the possibility of structuring this in such a way that a flawed critique won't win the money, but yet it is unarguable that a cogent critique WOULD win the money. Only then (and increasingly, the longer no critique appears) is there a credibility win for SENS. Do you agree? How to actually achieve such a structure - well, as I say, we're working on that.

[John Schloendorn]

That could be a bit of a problem. You're saying that anyone who is not you cannot critique SENS without being paid money to be sent back to study, but you are saying that someone can critique the critique without problems... While this can be more than 0% consistent, I guess it cannot be 100% consistent no matter how clever you try to hide it.

So basically, I'm saying do it, but do not invest excessively. Do invest excessively in projects that are 100% consistent. In the end it should be Dave or whoever's money it is who quantifies this idea.

[ag24]

I may not have made clear the scenario I'm concerned to avoid. What I don't want to happen is for one of my esteemed colleagues to write something that is utterly full of holes but subtle ones. Things like "Putting the mtDNA into the nucleus is hopelessly ambitious because we know so little about know how mitochondrial transcription and translation are regulated", for example :-) Or "We've been trying rather hard to cure cancer for over 30 years and we've hardly progressed at all", or "You can't put bacterial genes into us, the immune system will go crazy", or "Gene therapy sounds easy in principle but so far all it's done is kill people" (forgetting that we're quite good at it in mice), or "We still have this blazing controversy about whether aggregates even cause Alzheimer's" (forgetting that my whole point is to fix everything that even MIGHT matter), or "Anyone who thinks we can totally eliminate aging in a few decades doesn't understand biology at all" (forgetting about escape velocity). You get the idea. A critique of this sort that was perceived as cogent would do a lot of harm to SENS despite any rebuttal, just as Caliban says, and especially so if it appears in TR because it is likely to be viewed as unbiased, just as Prometheus says.

So -- what we're thinking about is something where the winning of the money is dependent not only on writing a one-off critique but on the outcome of a written exchange (perhaps some of it written only online, but that's a detail) in which I get a chance to rebut such points, the writer gets a chance to rebut my rebuttals, etc. What I mean by "outcome" is that there needs to be a person or persons who vote up and down whose position they find the more convincing. Those people also need to be seen as unbiased, of course -- but if winning the money is dependent on the cogency of the argument, Caliban's point is (I think) quite powerfully defused -- a broken critique doesn't achieve credibility, and SENS is not damaged by it. This is not quite the scenarion Prometheus mentioned of a prize for the most potent critique - it just means the critique has to be potent enough to deserve the money.

The other point to bear in mind is that the question is not really whether SENS will work in the timeframe I suggest: the question is whether SENS is currently our best bet (better than just continuing to slog away at understanding aging in more and more detail, and better than CR mimetics or antioxidants or telomere reconstitution). This means the odds are of course strongly stacked in SENS's favour, but that's fair, because the private position of most of my colleagues (the one that got Pontin into this mess) is that SENS is not just wrong but crazily wrong.

Supposing we did something like this: any suggestions as to who the jury should be?

[John Schloendorn]

Can't you just have a meeting with the guy? You present, the gerontologist asks, you chatter a while about it, and then you grant him sole authorship? I mean it sounds quite normal to me when you write about someone's work, to first interview him. Alternatively he might contact you from time to time while writing to give you a chance to explain/rebut. Unless he's really malicious, he won't put anything in the essay that you did not talk about, will they?

[ag24]

Nice idea John, but a couple of disadvantages relative to the scheme I outlined:

1) "The guy" has to be chosen in advance. If he then produces something reasonably positive, other gerontologists can just dismiss it as that he didn't try very hard or he was being charitable, i.e. nothing really changes except that the money and opportunity are gone. This is a real risk, because it's what has happened re the people who signed up to my first two SENS papers. With my scheme, you have to put up or shut up.

2) A rather likely outcome is that we agree to disagree. In that case, it should be up to neutral observers whether the guy has made a compelling case, because if he gets the money despite neutral observers thinking he didn't make a case, we're back to the situation of having spent money only to have SENS undeservedly harmed. If getting the money is contingent on making a compelling case, a failled attempt (a) helps SENS's credibility and (b) retains the money for someone else to have a go, fail, and help SENS's credibility even more.

[caliban]

Apologies for misunderstanding the proposal.

So to be clear, you would want to issue a "challenge prize" like
http://www.csulb.edu...astrop/faq.html

(while that specific prize is maybe a tepid analogy, one gets the idea re how to conduct and argue for it.)

Clear merit of such a challenge is that you can always point to it, and realistically no-one is likely to take it up, if only because your opponents will suspect the thing to be rigged anyway.

That means you could put up quite a lot of money, because it is unlikely to ever be spent.

It also means that you have to go to extreme length to demonstrate that the challenge is fair and unbiased.

[ag24]

Many thanks Caliban - what an absolutely remarkable document. The phrase "He chose to hide in the bog of his Blog" is one of the most memorable I've seen in months.

Yes, broadly that sort of prize - except more so, in that the challenger would not have to put up any money of their own.

The question of who is the judge (or jury) - how they are chosen - is the hardest one in making the challenge seen to be fair, and these people haven't really addressed it either. I remain interested in ideas for that.

[John Schloendorn]

1) Other gerontologists can dismiss a judge for the same reasons. Why would a judge make a difference? No judge enjoys an even higher reputation among senior gerontologists than a senior gerontologist.
In my opinion the challenge prize concept sounds dodgy to the bone. It's not by accident that it was developed by creationists. You can't sell something as good science that is obviously designed to prove something specific. Science is supposed to consider the evidence and then reach a conclusion. That is what you did up to now with huge success. I'm pretty sure that giving it up will cost you respectability among your colleagues.
Have some confidence in SENS. If it is as good as we think it is, then why would you "agree to disagree" with a leading expert in the field who really understand it? If you did, then that would be a reason to go back to the drawing board rather than to continue insist on SENS's infallibility.

2) Having repeated failures actually help SENS does sound good, and I'm sure those creation people think alike. But I agree with Caliban:

realistically no-one is likely to take it up, if only because your opponents will suspect the thing to be rigged anyway.

I strongly favor a cooperative and communicative course of action over threatening innocent gerontologists with the court... A single positive endorsement may not be the big breakthrough, but as I said above, sustained repetition from different sources is getting there slowly, but it's always getting there.
And don't forget about the single senior who sits down to study SENS. I hear you say that your major problem is that they don't. If your own theory is right, and this helps to convince the guy, he might become a huge supporter of the movement and we might consider repeating it. Costly but perhaps effective [thumb].

[John Schloendorn]

Nonetheless, as for possible judges... They should be experts on the science, but from outside the academic biogerontology community to avoid bias, so the business and law sector come to mind. Maybe enterpreneurs like Mike West or Bill Haseltine? Or perhaps one can find an actual judge with a background as a biotech lawyer?

[golddragon]

When I was a med student there were prizes offered for essays. University is the time people:
1. Need money
2. Have time
3. Are learning lots of new stuff
4. Are not (too) biased
5. REALLY want to get their name in print
Perhaps this would be a better approach. We could offer it up to biology/med students for critique, and offer a prize +/- publication for the best critique in each area.

This could also be run in rounds. With a website providing all submitted essays, thus increasing the quality with each round
1. Critique SENS (antiSENS)
2. Critique antiSENS
3. and repeat
4. or change topic eg Additional Proposals for TREATING aging
David

[caliban]

regarding potential judges, there are three options

1)
You want a hyped peer review, in which case any biogerentologists of statute who have not taken sides would be possible. However, this approach won't make you any more popular in the community.

2)
People of statue pre selected, as John suggest. There will always be some potential bias or at least much of the communiation will center around these judges.

3)
A system where both you and your opponent suggest judges to which you must mutually agree.


As a lawyer, I'm a bit partial to (3), while most scientsts would probably go for (1) by instinct.

[jaydfox]

I like golddragon's suggestion, perhaps not as an alternative, but at least as a supplement. We've started a similar process right here in the SENS forum, where Prometheus (and to a lesser extent, myself) critiqued SENS, and Dr. de Grey (and, to an extent, Michael Rae) rebutted. Some new issues were brought up, and some old ones that rehashed issues that had been discussed elsewhere (which previous discussions were not known to most here).

I'd like to see a similar idea, with good critiques from knowledgeable graduate/postgraduate students, with a chance at publishing (even if only in RR, which will be seen as a biased journal by de Grey's critics, but it's a journal nonetheless).

As a background, Aubrey could perhaps provide an intro article discussing the common no-no's explained in detail (like the list de Grey provided, see below). Then set forth the challenge to critique, with good critiques (i.e. critiques which raise novel issues, etc.) to be published. And like golddragon suggested, we may as well have the competitors write the rebuttals as well when possible (obviously not the same competitors, but e.g. have competitors A, B, and C write critiques, and B and D, and E write rebuttals, where B rebuts A, and D rebuts B, etc.) And of course, if no rebuttals to a particular critique or issue come forth in a certain timeframe, then have e.g. Michael Rae or Aubrey himself do the rebuttal.

As for common no-no's, Aubrey hinted at such a list. He could lay it out in generalities (the types of no-no's), and then put in specific examples in more detail than what appears below:

What I don't want to happen is for one of my esteemed colleagues to write something that is utterly full of holes but subtle ones. Things like "Putting the mtDNA into the nucleus is hopelessly ambitious because we know so little about know how mitochondrial transcription and translation are regulated", for example :-) Or "We've been trying rather hard to cure cancer for over 30 years and we've hardly progressed at all", or "You can't put bacterial genes into us, the immune system will go crazy", or "Gene therapy sounds easy in principle but so far all it's done is kill people" (forgetting that we're quite good at it in mice), or "We still have this blazing controversy about whether aggregates even cause Alzheimer's" (forgetting that my whole point is to fix everything that even MIGHT matter), or "Anyone who thinks we can totally eliminate aging in a few decades doesn't understand biology at all" (forgetting about escape velocity).

As a bonus, if this program is successful, it could lay the groundwork for challenging senior biogerontologists, by saying that the academia is ahead of the curve, and they are behind the times, by not even given SENS the time of day. Couple that with an honorarium/challenge prize, and it could be more effective. Or I could just be loony...

[jaydfox]

The other big no-no that should be mentioned is entropy. It drives me up the wall when people (like Estep) bring up entropy. Entropy is a theoretical barrier against indefinitely prolonging life, and against indefinitely halting aging, but it's not a barrier against radically extending lifespan, let alone merely "significantly" extending lifespan.

And that's the problem. Just because entropy is a barrier against a googolplex-year lifespan, that doesn't make it a barrier against a 200-year-lifespan. But when entropy is mentioned, this distinction is never made. They just say that entropy will eventually win the day, so SENS is impossible.

Rubbish!

Edit: fixed spelling of googolplex

[Mark Hamalainen]

As a background, Aubrey could perhaps provide an intro article discussing the common no-no's explained in detail

What about a new book? Something along the lines of your Mitochondrial Free Radical Theory book, but for all of SENS. Easier said than done of course but... the medium in which you deliver your message is very important. A number of scientists I know are unwilling to read SENS simply because it is presented on a website (a bias that is dying out with our generation, but still has a strong hold on the scientific community). I do have some sympathy for them, a book is something real and unchanging, that you can take with you and read wherever you are. Taking the court analogy, the book could then be your case, to be judged by a number of reviewers that you give financial incentive to. Having all of the information in one place will make it easier for them. Plus, this would be a more respectable method than holding some sort of mock trial (although I think that would be a lot of fun).

Getting a review (or perhaps a special feature with multiple reviews) published in Nature would also be good publicity.