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mutations of dna


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#31 opales

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Posted 10 August 2006 - 02:10 PM

Again, good intentions and rhetorics, but you will not have "scientifically debated" SENS before we see your paper in rejres or elsewhere (med hypotheses?). I have confidence in your ideas and am sure the better ones of them will be publishable if you invest the effort to organize them better and mount a coherent defense.


While peer review has its perks, it also has some drawbacks too; namely, it is freakishly slow. While it is a judgement call what is deemed important enough to warrant a publication and review, for practical purposes it is better to express and debate many issues via less resource and time consuming media.

I think Aubrey is judging Prometheus' efforts undeservedly harshly. The discussion on GRG list was one the few debates aimed at critiqueing and improving SENS since I have been around, and the overall interest and participation it received among the very people we want to be interested (gerontologists) was surely net positive for SENS agenda. Aubrey must agree that scientific debate on specific issues of SENS is exactly what we want, especially if done through courteous (albeit perhaps repetitive) argumentation, unlike, say, any of the SENS Challenge submissions (and the follow-ups by Estep himself) which quite frankly were embarassing in their unsubstantiated ad hominem tone.

#32

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Posted 10 August 2006 - 02:10 PM

Again, good intentions and rhetorics, but you will not have "scientifically debated" SENS before we see your paper in rejres or elsewhere (med hypotheses?). I have confidence in your ideas and am sure the better ones of them will be publishable if you invest the effort to organize them better and mount a coherent defense.


I do not need to publish a paper in a journal for my views to contain scientific validity. If you question the scientific merit of my arguments then do so here in these fora. I am not sufficiently motivated to invest the time to compile a theoretical paper to critisize SENS. This is largely because I have nothing to prove - I am not anti-life extension, I am not anti-SENS and neither am I trying to make a name for myself by this agency. I can see logical flaws in SENS and I am pointing them out. I am compelled to do this because it is congruent with my code of ethics. Your resort to criticizing my "rhetoric" rather than the substance of my arguments diminishes yours and SENS's credibility and threatens to undemine the pereception of competence of the leadership behind SENS. I sense an underlying sense of hostility (that invariably stems from fear) and frankly I do not see the reason for it.

WILT is dead John. It is important to have the courage to aknowledge this and move on (to other solutions). Similarly AE is in a precarious position when considered in the context of mitochondrial autophagy modulation.

Remember, when it comes to achieving escape velocity it is not the journey that counts but reaching the destination.

#33 caston

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Posted 10 August 2006 - 02:25 PM

Caston, a peer-reviewed journal has the primary function to filter out pseudoscience and outright junk, so people don't have to waste as much time researching what's junk and what isn't.


Would the SPAM filter analogy be appropriate? Sometimes you need to check your junk mail folder to see if something legitimate got sent there incorrectly.
A scientific advance tomorrow may be ignored by established scientists today.

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#34 John Schloendorn

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Posted 10 August 2006 - 02:56 PM

Prometheus,

I do not need to publish a paper in a journal for my views to contain scientific validity.

No, but a journal offers to provide some check for you and others that this is true -- free of charge! Putting your ideas in a coherent form is necessary anyway. Writing a paper in a journal is an opportunity to get help with this difficult task, not an after the fact nuisance, and on top of that a chance to reach an audience you could not otherwise.

Your resort to criticizing my "rhetoric"

Not criticizing it, I said it's good.

WILT is dead John. It is important to have the courage to aknowledge this

I do not have enough knowledge to make any prediction on this.

when it comes to achieving escape velocity it is not the journey that counts but reaching the destination

One cannot reach a destination without first mastering the journey.

Caston,
Yes, the idea of imminsters making a true contribution on the fora is romantic, but 99.99% of the time it simply did not work that way, least of all in bioscience. If this is an exception, then an organized formulation of the ideas is necessary to allow others to recognize it.

Opales,

unlike, say, any of the SENS Challenge submissions (and the follow-ups by Estep himself) which quite frankly were embarassing in their unsubstantiated ad hominem tone.

And you think when Aubrey responded to multiple points all over the fora, even repeatedly, this qualifies as ignoring someone? They may not have reached an agreement, that happens all the time in academic discussion, but the term "ignore" is totally inappropriate.

#35

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Posted 10 August 2006 - 03:01 PM

> A good starting point:
>
> The Cui mouse.
> The newly discovered role for hTERT.

Less than a month ago I replied to you on both of these points at the GRG list. If you didn't want to waste my time you could have copied those responses to here (as I do below), rather than accusing me of not responding. I deduce that you either want to waste my time or have the memory of a below-average ant. Which is it?

my emphasis

Dangerously close to ad hominem Aubrey. The reason I bring them up is becuase your responses were miserably inadequate in consideration to their implications for SENS.

Let us revisit them: Firstly on the Cui mouse (the cancer resistant mouse whose cancer resistance is transferable to normal mice),

======================

Date: Mon, 17 Jul 2006 21:29:20 +0100 (BST)
From: Aubrey de Grey
Subject: [GRG] Re: SENS: Aubrey Responds to Harold
To: grg@lists.ucla.edu

Harold wrote:

...

> (incidentally, I think the discovery by Hicks et al 
> (PNAS 2006 v103 n20) highlights that the direction we should be 
> looking towards for a cure for cancer has more to do with immunology 
> rather than telomerase downmodulation or in SENSspeak, interdiction).

I'm well aware of the various approaches to cancer immunotherapy and
they are certainly very exciting, but they are also a long-established
cancer therapy field that has not delivered much.  I'll be as keen as
anyone to see what the Cui mice end up telling us when their genetics
are better elucidated, but I'm not betting my life on them.


The discovery by Hicks et al refers to a strain of completely cancer resistant mice that were discovered 3 years ago and were recently reported to be able to transfer that resistance to normal mice by a single transplant of white blood cells. This is a sensational discovery pregnant with numerous implications for a cure for cancer in humans. Aubrey just dismisses it like it was a yesterday's news. He refers to elucidating their genetics but their genetics have nothing to do with this - since the resistance is mediated by their white blood cells and astonishingly it is transferable. No gene therapy, just a simple blood transfusion. The human solution is obvious we need to launch a program to identify cancer resistant individuals in existing human populations, isolate their white blood cells and determine if cancer resistance can be as easily transferable. A wonderful opportunity!

...

> Speaking of which, how do 
> you reconcile the observation that hTERT has a mitochondrial 
> localization sequence in a WILT context?

Lots of things have mitochondrial localisation sequences for unknown
reasons, because those sequences are very loosely defined -- it was
once determined that 10% of all coding sequences would act as such a
sequence.  For all we know, hTERT is localised to mitochondria only
by accident and because there is no selection not to do this.  There
is certainly no reason to ascribe it a mitochondrial role solely on
the basis of its localisation, and the finding that nonphysiological
hTERT expression sensitises cells to stress-induced apoptosis tells
us nothing either, since the physiological level of hTERT in any
compartment of the cells in question, stress or no stress, is zero.


Once again the casual dismissal but this time it is accompanied by the whimsical statement: lots of things have mt localisation sequences -- but that would imply that mitochondria would be filled with all sort of useless proteins, which is not the case as the contents of mitochondria have been reasonably well characterised. He completely ignores the findings of the cited research -- that hTERT increases sensitivity to ROS in mitochondria -- and makes up his own reason as to why hTERT may be there (by accident!). Astonishing.

I am beginning to sympathize with poor Estep.

#36 John Schloendorn

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Posted 10 August 2006 - 03:20 PM

Allright, I'll have a shot at these too:

Cancer:
The project you envision is nascent. It is rumored that Cui identified some individuals with leukocytes that behave similarly to the mouse leukocytes in vitro), and this is very exciting. People are working on it, very potent potential supporters are aware of it, and if we are ridiculously lucky, they will cure cancer. The same is true for several other groups' work (e.g. certain types of adaptive immune therapy, or telomerase inhibition). What's wrong with anyone trying the same with their particular ideas?

mito-hTERT:
This too is a single and interesting result, which requires more research to become meaningful. It may turn out that loss of the function to which this study points would be very detrimental in humans, but it may also be that it is not. This should be investigated, and WILT depends on more than this one insecurity. There is simply no more one can know about mito-hTERT before more data becomes available, and more data is being worked upon. Therefore, it is not yet the time to massively therorize about this phenomenon, just like countless other single results at the forefront of our expanding knowledge, which are also no part of SENS. Give it time, in biotech one can't shoot as soon an in vitro suspect of a target comes in sight.

#37

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Posted 10 August 2006 - 04:12 PM

Cancer:
The project you envision is nascent. It is rumored that Cui identified some individuals with leukocytes that behave similarly to the mouse leukocytes in vitro), and this is very exciting. People are working on it, very potent potential supporters are aware of it, and if we are ridiculously lucky, they will cure cancer. The same is true for several other groups' work (e.g. certain types of adaptive immune therapy, or telomerase inhibition). What's wrong with anyone trying the same with their particular ideas?

Correct me if I'm wrong but isn't SENS and the MPrize about finding solutions to aging as soon as possible? Is the sense of urgency associated with marketing purposes only or does it also apply to implementation? Therefore, if a hint at a solution presents itself should it not receive more attention - particularly a solution for a profound a problem as that of cancer? Should the SENS team perhaps be looking at collaborative efforts to accelerate discovery at the areas with the highest ROI?

#38 John Schloendorn

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Posted 10 August 2006 - 04:35 PM

True, ROI is one criterion, but there are others, almost equally important, namely lack of academic attention in the mainstream, and low fundability by other sources (why this is so is explained on Aubrey's web page). Cui scores relatively high on the first criterion, but not at the other two.

Therefore, I feel the limited MF resarch resources can make more of a difference in Lyso and Mito SENS, currently.

#39 John Schloendorn

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Posted 10 August 2006 - 04:44 PM

A broadening of the MF's scope by lessening the importance of the latter two criteria has been brought up every now and then, but can be seriously considerd only after our research resources see a dramatic increase.

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#40

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Posted 10 August 2006 - 04:45 PM

Would it not add credibility for SENS to align itself with some mainstream (and fundable) research such as the Cui mouse?

#41 John Schloendorn

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Posted 10 August 2006 - 04:48 PM

Yes, to the Methuselah Foundation. This is one reason to consider the above-mentioned broadening of scope once we can afford it.

#42

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Posted 10 August 2006 - 04:54 PM

The Cui mouse initiative could be as simple as creating and marketing a website that tracks genealogical data related to causes of death in families to seek to identify individuals where there is evidence of cancer resistance. For example, candidates could be selected from those whose parents, grandparents and great-grandparents died at an age greater than 75 from non-cancer causes.

#43 John Schloendorn

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Posted 10 August 2006 - 05:04 PM

I am not aware of Cui's current agenda and plans, but think that it would make sense for him to proceed (or have proceeded, if the above-mentioned rumor is true) somewhere along these lines.

#44

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Posted 10 August 2006 - 05:08 PM

Is there interest in a collaboration between the MF and Cui?

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#45 John Schloendorn

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Posted 10 August 2006 - 05:14 PM

Speaking only for myself, I find his results extremely exciting and can't wait to hear more. However, given my resources and occupation, I do not see much overlap between our activities that could be the grounds for a collaboration. As Cui's results mature, and perhaps so will my position in the Methuselah Foundation, I might become more interested in pushing along these lines, but that really depends on future developments. I hope other foundation volunteers will answer for themselves.




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