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The SENS Challenge


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83 replies to this topic

#61 jaydfox

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Posted 11 July 2006 - 04:34 PM

Ah-ha!

I had another copy in the other laptop, and copied it the "correct" way this time.

Here's the file I copied from my cache:

Edit: Sorry folks, only got the first of three pages. If anyone has the other two cached, please copy them from your cache ASAP, before you try to view the pages.

Attached Files



#62 ag24

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Posted 11 July 2006 - 04:48 PM

No panic folks - they've clearly got general technical problems, I've found some other AWOL articles too. I'm sure it'll all be back within the hour.

#63 ag24

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Posted 11 July 2006 - 05:09 PM

And indeed, it's back. Hm, Estep has replied to my comments already...

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#64 ag24

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Posted 11 July 2006 - 05:43 PM

> I don't have my finger on the pulse of the gerontology community, especially Aubrey's detractors.
> Aubrey, do you think they focus solely on your version of SENS, both its intended targets and its
> suggested (theoretical) solutions? Or do they see the bigger picture and mock it as a whole?

There's a range. My most energetic detractors certainly think that the number of implausibilities in SENS is quite sufficient to demonstrate that nothing remotely like SENS could ever work. Other people think that most of it seems pretty reasonable but that some components (especially WILT, of course) are infeasible and/or some unaddressed aspects of aging (especially non-oncogenic nuclear mutations or epimutations) need to be addressed. I hope that the latter issue will make progress once my paper on it comes out.

#65 John Doe

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Posted 11 July 2006 - 11:00 PM

Congratulations, Aubrey! It is thrilling to see your work survive peer review like this, even if the results were somewhat mixed.

My attitude is like Jay's: Aubrey may not be perfect but his mission is so crucial and so important, that his ideas deserve debate. I decidedly a long time ago that I was not enough of an expert to determine whether SENS was a good idea, in all respects, although I suspected that the more ambitious parts (e.g. curing cancer) were perhaps misguided. But where I remained confident, and this confidence brings me comfort and solidarity with Aubrey's cause, is in the ethical dimension of Aubrey's work. SENS may fail spectacularly but, if our species continues to progress to the point of curing aging, Aubrey will still be remembered as a prophet---an ethical prophet. I dare say he will be like Gandhi or Martin Luther King even if he is not like Louis Pasteur and the Wright Brothers.

Despite the cloudiness of the SENS debate, I understand enough to know that Aubrey has excellent rejoinders to many of his critics. When Aubrey says:

"To quote them: “If we could easily predict the outcome, why bother going through all the trouble of actually doing the engineering?”. I wonder if Estep et al. think the Wright brothers built their airplane in order to discover whether it would fly? I personally suspect that they built it because they were confident that it would fly and they wanted to build something that would fly. Estep et al.’s oversight of this motivation is quite breathtaking to anyone who understands that, since aging causes immense suffering and death, it is something to be explored not for the sake of curiosity alone but with the goal of actually doing something about it."

This rings true to me. And even if Aubrey is wrong on one or more elements of SENS, why should we throw away the baby with the bathwater? Why is the idea that SENS can be *fixed* so intolerable? He's just one man, for God's sake! If we invested a fraction towards curing aging of what America invested in putting a flag and a car on the moon, could we not fix SENS?

The heated rhetoric suggests that the critics were motivated by emotion as much as reason. This is a bizarre, if not a rare phenomenon---a sort of death wish. If anything, emotion would incline me to put my faith in Aubrey, not againt him. I don't want to die. And I suspect that enthusiasm for life extension will reach a critical mass, to overcome this widespread cognitive dissonance, and I hope to see it in my life time.

Edited by John Doe, 12 July 2006 - 06:22 AM.


#66 John Schloendorn

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Posted 11 July 2006 - 11:52 PM

Aubrey will still be remembered as

Hah, hopefully the time when people "are remembered" will be over in his lifetime!

#67

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Posted 11 July 2006 - 11:55 PM

Thanks Jay.  I am a little tired of being described here as exhibiting disregard for experimental evidence, when I painstakingly address every single item of experimental evidence that others bring to the table. Interpreting experimental evidence as meanng something other than what the experimenter said it meant is not disregard.


No offence intended. "Disregard" may be misleading since it conveys the act of ignoring and clearly not only have you not ignored the said studies (related to DNA damage and aging), you have devised robust alternative interpretations. In fact you have a close relationship with one of the world's foremost experimentalists on DNA damage - Prof. Jan Vijg - which makes your conclusions even more exasperating. Perhaps a more appropriate descriptive would be fanatical avoidance of the obvious? :)

Congratulations to Aubrey and his team, and congratulations to Jason Pontin who brought together an extraordinary panel of judges for this exciting collection of articles.

#68 John Doe

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Posted 11 July 2006 - 11:56 PM

Hah, hopefully the time when people "are remembered" will be over in his lifetime!


Good point! :)

#69 jaydfox

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Posted 12 July 2006 - 12:00 AM

No offence intended. "Disregard" may be misleading since it conveys the act of ignoring ... Perhaps a more appropriate descriptive would be fanatical avoidance of the obvious? :)

[lol]

#70 chubtoad

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Posted 12 July 2006 - 04:47 AM

Congratulations Aubrey. Hopefully the next debate you have will be on the best way to implement your ideas.

#71 Anne

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Posted 12 July 2006 - 05:57 AM

One of the most important results of this challenge judgement is the fact that attention was drawn to the inappropriateness of the "attack" method employed in the Estep submission. I think it speaks well for science overall that these judges counted that aspect of the submission as a negative.

While I realize that this is by no means a guarantee that SENS will get further funding, or that it will work, I do recognize this turn of events as a positive outcome and one that surely cannot hurt the cause of anti-aging research. Congratulations to Aubrey is, in my mind, appropriate!

#72 kevin

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Posted 12 July 2006 - 06:10 AM

I've contacted a few blogs about the Challenge results... Have a look around tomorrow and see if there's anything worth commenting towards.. Hopefully Instapundit picks it up..

#73 jaydfox

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Posted 12 July 2006 - 07:50 AM

I finally broke down and set aside an hour and a half to read Estep's submission, de Grey's rebuttal, and Estep's response.

Intense shitfight, if you ask me. de Grey doesn't sink as low, but the implied (as opposed to Estep's explicit) ad hominems still run thick. Overall, I think de Grey wins for style, but I suppose I can't say I'm unbiased.

As for content, I'd have to read all the supplementary material and references, which of course I'm not going to do.

But based on the arguments Estep et al. put up, here's my take:
The only points they made any traction on were nDNA mutations and (especially) epimutations, and WILT.

Before I address these, I'd like to point out that their arguments against allotopic expression and bioremediation were poor at best. de Grey handily answered these points in his rebuttal, so I'll move on to the response.

Estep et al.'s response to de Grey is even more puzzling. They basically admit that their statement:

even if accomplished, there is insufficient evidence to conclude that mitochondrial genome decay limits cellular or organismal life span more than other molecular pathologies within these same cells, e.g. non-oncogenic decay of the nuclear genome or epigenome

was basically there to fill space, as it certainly wasn't an argument. They then proceed to more hand-waving about how difficult the problem is, without explaining why it's so difficult. "It's just hard. We say so."

They then move on to microbial hydrolases. It's hard to judge here, because they dive into technical territory I haven't yet ventured. But it sounds like they're just saying it's hard again, not that it's impossible. By way of example, they're saying that it's the kind of "difficulty" an engineer would have in designing a rocket to go to Mars using only chemical propellants (i.e., no "nuclear" shortcuts, etc.), as opposed to the kind of difficulty of designing a single-stage rocket to go to Mars. The latter is clearly much more difficult and borders on impossible for scientific reasons (simple math, really, the amount of fuel needed would be tremendous, and the structure would have to be so light that it would be impractically fragile). The former is simply difficult from an engineering perspective (witness the gigantic effort it took to get to the Moon in the 1960's, let alone trying to get to Mars), but not obviously ruled out by our current scientific knowledge.

de Grey isn't proposing something obviously nearly impossible (e.g., single stage to Mars with chemical propellants). He's proposing an engineering problem that's very difficult (e.g., a rocket [perhaps three stages] to Mars with chemical propellants).


But where Estep et al. made some traction was on nDNA damage and WILT. Mind you, it's not that they pointed out anything new to us. It's just a helpful reminder that SENS as currently constructed faces the grave risk that nDNA damage will be demonstrated beyond a reasonable doubt to matter to aging, perhaps even sufficiently to warrant a change in stance from de Grey. But does that mean that SENS, as a model or prototype of a way of adding decades to human lifespan, is useless in its present form? Surely it couldn't be that difficult to add a strand to SENS to deal properly with nDNA damage. If the goal for effecting escape velocity is to add, say, two decades to lifespan, then isn't it fair to say that even a moderate improvement in nDNA health—say from the nDNA profile of an 80-year-old to the nDNA profile of a 60-year-old—would be sufficient to help out in this regard? Remember, the strands of SENS have never been claimed by de Grey to cure aging: they simply buy enough time to allow the next generation of biotechnology to add even more decades, ad nauseam. They don't need to be perfect; they just need to be good enough.

On WILT, they rightly point out that there are complications with removing telomerase. On one front, they suggest an increased frequency of certain cancer types, which is hardly surprising. What they fail to grasp is that, while the number of such cancers might increase, none of the tumors should survive long enough to become life threatening. What's life-threatening to a mouse isn't relevant to what's life-threatening in an organism 10,000 times bigger. For one, cancers don't need to metastasize in mice to become life-threatening; in humans, metastasis is the norm for life-threatening cancers.

On another front, they point out that one of the subunits of telomerase has non-telomere-regulating functions, and deleting it could compromise stem cell health. I believe de Grey has covered that one before as well, somewhere in our SENS archives, but I've lost count of the number of uses for telomerase: telomere lengthening, stem cell mobilization, DNA repair enhancer, apoptosis inducer, etc., etc.

Actually, in looking back, I suppose they didn't make as much traction on WILT as I thought. It sounded impressive, but it's nothing new. At any rate, I don't actually expect WILT to be used in mainstream medicine, but if, 20 years from now, it becomes clear that it's the only available way to deal with cancer, then at least it'll have been pondered over and researched.

#74

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Posted 12 July 2006 - 09:15 AM

On WILT, they rightly point out that there are complications with removing telomerase.


More complications that even they realize (see The Telomerase Apocrypha - that study sunk WILT). If you want to speculate on how to deal with cancer look towards that extraordinary strain of cancer-resistant and cancer-resistance-conferring mice that was recently reported (see cancer cured in mice).

Given the state of WILT,

Surely it couldn't be that difficult to add a strand to SENS to deal properly with nDNA damage.



#75 Da55id

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Posted 12 July 2006 - 04:16 PM

whacka meme -
hit the Digg button to boost the story.

http://digg.com/gene...ence_or_fantasy

#76 Live Forever

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Posted 12 July 2006 - 05:31 PM

whacka meme -
hit the Digg button to boost the story.

http://digg.com/gene...ence_or_fantasy

Some of the comments are good, and some are kind of pathetic.

#77 eternaltraveler

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Posted 12 July 2006 - 05:39 PM

http://www.livescien..._challenge.html

#78 noam

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Posted 21 July 2006 - 06:32 AM

Very surprising results.

In an earlier post I admit that I didn't believe such result was possible. I simply couldn't see how a panel of non-gerontologists could dismiss the Estep et al paper, given the high credibility of its authors in the field of gerontology.

I think the $10,000 was given out of respect. If you read the opinion of the judges you see that this half prize wasn't justified according to the challenge rules. But still, we are talking about a paper written by the front of the gerontologist community, so some respect must be given (In a molecular biology of aging course that I took last semester, the professor tried to portray the ground braking discoveries in this field during the last years, and we were taught several papers which were written by some of the guys who wrote the Estep rebuttal, so still a lot of respect to these guys).

I think now will be the appropriate time for Jason Pontin to publish an editorial in the upcomming issue, dedicated entirely to an apology to Aubrey, for his original editorial (that started this whole thing), where he decided on his own that SENS is unworthy of learned debate (called Aubrey a Troll, etc.). Unlike Estep, Pontin can't hide now behind the excuse that the judges weren't up to the task, since he could have stopped the challenge at any point if he thought so.

Edited by noam, 21 July 2006 - 03:23 PM.


#79 jaydfox

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Posted 21 July 2006 - 03:58 PM

Well, if you read the article announcing the decision, you'll see that while the submissions failed to meet the conditions of the challenge, the panel of judges said things about SENS that Pontin will claim discredit it nonetheless. Pontin will claim that failure to "lose" the challenge doesn't necessarily mean they "won" the challenge, since the panel of judges had harsh remarks for SENS as well.

For me, the victory isn't so much the outcome, since it was a mixed result, as far as PR: bad things were said about SENS, and half the value of the prize (note: not half the prize, just half the value of the prize) was awarded. That can be spun as a non-victory by SENS's detractors.

For me, the victory is getting what looks vaguely like a scientific debate (and for the general public, I suspect it'll look a lot like a scientific debate), and it's on record, and it's by respected researchers.

What's more, the respected researchers can no longer hide behind the claim that SENS isn't worthy of debate. They can claim it's wrong, though that'd be their mere opinion until backed up by scientific evidence, etc. But it's not "so wrong that it's unworthy of learned debate".

Aubrey has traction now, and I suspect he'll use it well in the coming year or two to continue to draw out his detractors to make cogent arguments. Put up or shut up, as they say.

#80 noam

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Posted 22 July 2006 - 06:48 PM

I read Pontin's editorial again now, and he actually raise the possibility that SENS is possible. So I guess no apology is needed.

His main gripe was that we shouldn't try to dramatically extend human lifespan, because above all we must stay "humans"... i.e the *only* orgaism on earth who dies from aging. He believe we must cherish this new unatural state of death-from-aging (which ironically happened because of our technology increase in the last several centuries).

Edited by noam, 22 July 2006 - 07:00 PM.


#81 MichaelAnissimov

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Posted 22 July 2006 - 11:51 PM

Aubrey rules! Heh, just had to say it. Now, the question is... is it more worthwhile to contribute to the MMP or LysoSENS? Personally, have more confidence in John than the scientists who might win the MMP. Aubrey, are you thinking about doing research, or do you plan to spend the coming years touring to promote SENS?

whacka meme -
hit the Digg button to boost the story.


Do you realize that the ImmInst community is big enough to digg a story to the front page whenever we desire it? Really! This is tremendously powerful, and we are failing as I speak by not taking advantage of it.

#82 Live Forever

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Posted 23 July 2006 - 12:11 AM

Do you realize that the ImmInst community is big enough to digg a story to the front page whenever we desire it?  Really!  This is tremendously powerful, and we are failing as I speak by not taking advantage of it.

Excellent point Micheal! I have often thought that if there could be a way to dissiminate information effectively to a large number of transhumanists, stories could be dugg, books and movies could be rated, polls could be influenced, comments could be left, etc. on a wide variety of different sites and topics casting transhumanism in more of a positive light, or otherwise getting information out, influencing countless individuals in the process.

#83 ag24

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Posted 23 July 2006 - 09:51 AM

We are indeed working to ramp up funding for SENS research (not only LysoSENS) as soon as possible. I won't be doing any research myself - that would be a very nefficient use of my time. We will also be continuing to work to grow the MMP fund.

#84

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Posted 23 July 2006 - 12:47 PM

I won't be doing any research myself - that would be a very nefficient use of my time.


God forbid.. Only kidding. Keep up the good work!




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