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#1

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Posted 27 February 2005 - 03:05 AM


Michael Rae, in "The Birth of NeoSENS" topic sums up his position:

The central feature of SENS per se as an approach to biomedical gerontology is to directly attack the accumulating damage that causes dysfunction, rather than attempting to prevent it ..


I would say Michael, that WILT, which attempts to prevent cancer and the proliferation of other unwanted cells by ablating telomerase expression is also acting as a preventative, because it prevents cells from dividing uncontrollably is it not? How about allotopic expression of mitochondrial DNA - is not the objective there to prevent DNA damage by transferring the mitochondrial genome into the less ROS rich environment of the nucleus?

There is a word, Michael, that describes what you committed in the above statement - hypocrisy . The dictionary defines a hypocrite as one who is a false pretender to virtue or piety . It makes one wonder how pervasive this type of thinking and reasoning is.

I have never been interested in deconstructing SENS and revealing its flaws. But the sheer arrogance, disdain and contempt to even consider the merit of proposed more direct and productive methods of achieving negligible senescence compel me to do so. What are the motives, I wonder, of such behavior other than to obfuscate? What purpose does it serve other than to illustrate that the edifice of SENS must indeed be crumbling?

Other SENS supporters have defended its inflexibility on the basis that debates on implementation are not needed, since the prime imperative is to mobilize the support of the public. Let's hear it then - is SENS a marketing ploy or a real project to address senescence? Because if is a real scientific effort then it must welcome scientific scrutiny and have a mechanism of cutting non-viable hypothesis and attaching new innovations as they come forth. There is no such mechanism or any interest to create such a mechanism.

#2 reason

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Posted 27 February 2005 - 03:59 AM

Now this is the sort of approach that strikes me as unproductive. SENS is clearly a serious attempt to address the problem of aging, and any and all scientific debate is very necessary. It is not complete, nor is it anything more than the results of a comparative handful of person years at the moment - any serious final product needs far more than that, of course.

Scientific scrutiny is not posting to a messageboard, however, but rather is a matter is getting out there and publishing your critiques in a peer-reviewed journal. Don't confuse the marketing - which is largely aimed at getting scientists into the debate in journals in the first place - with either a) advocacy of a particular scientific position taken in advance of widespread, peer-reviewed contributions to the debate or b) advocacy for the need to get on and fix aging, however it ends up happening.

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#3 kevin

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Posted 27 February 2005 - 06:19 AM

Scientific scrutiny is not posting to a messageboard, however, but rather is a matter is getting out there and publishing your critiques in a peer-reviewed journal.


Hear hear..

One of the things which Aubrey is constantly reiterating is how rare it is that individuals provide him with any critique about SENS. I think you might be just the person to stir up a little interest in the scientific community at large concerning the in/feasibility of SENS should you wish to take your ideas and arguments to a higher and more recognized level.

#4 John Schloendorn

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Posted 27 February 2005 - 07:07 AM

Well said Reason and Kevin.

Prom: I would say that WILT can be understood to aim at reversing nuclear mutations and other damage, because the original proposal of WILT included the replacement of damaged cells with undamaged ones. Thus, as long as you do WILT, nuclear mutations will not have the chance to accumulate.
Allotopic expression attacks the accumulating damage in the mitos, by "obviating" it, or making it harmless, no matter how large it grows.

On the other hand, increased DNA repair would still suffer from the accumulation of the damage it seeks to address, albeit slower, which is good. But these are word games. I don't see the point in being so polemic. Go and publish your excellent ideas!

#5

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Posted 27 February 2005 - 09:44 AM

Allotopic expression attacks the accumulating damage in the mitos, by "obviating" it, or making it harmless, no matter how large it grows


(Well you would not want it to grow too large, John, because it may kill the host before the telomeric ends fray anyway (n^50)) ;)

That's one way of looking at it. Another way is that it is preventing the mitochondrial genome from being damaged. Similarly, enhanced DNA repair attacks molecular lesions, and can be said to attack cancer, apoptosis and aging. But you're quite right, John, these are word games and semantics. The objective is to engineer negligible senescence.

My objective is to ensure that it (DNA repair enhancement) finds its rightful place in the SENS collective and that the ponderous theory that nuclear DNA damage is solely responsible for cancer should be dispelled like the myth that it is.

Scientific scrutiny is not posting to a messageboard, however, but rather is a matter is getting out there and publishing your critiques in a peer-reviewed journal. 


And what is the purpose of these forums, Reason, if not for intelligent debate and discourse? And is there a more finer thing than keen minds getting together and unleashing ideas? Why are you, of all people, so afraid to consider an alternative viewpoint? This is not about some inane proclamation that lifespan can never or should never be extended. This is about ensuring that sufficient scientific substrate exists in SENS to be considered by the scientific community with the seriousness it deserves. Instead of reasonably science founded responses I encounter knee-jerk fear driven rhetoric - much the same as those you claim who are in the "death trance". There is nothing to fear about neoSENS theories. It is just a way of making SENS more palatable to the scientific community.


I think you might be just the person to stir up a little interest in the scientific community at large concerning the in/feasibility of SENS should you wish to take your ideas and arguments to a higher and more recognized level.


I don't see the point in being so polemic. Go and publish your excellent ideas!


In respect to putting these ideas together in a paper: The strange thing is, that aside from the evolution/mutation/DNA repair suppression concept which is an entirely novel theory, there is nothing novel about enhancing DNA repair. It is a natural consequence of something that scientists have known and been writing about for many years - that genomic instability leads to cellular dysfunction. Ironically, a colleague has only recently convinced me to co-author a paper on these very matters so it may appear in a journal after all. But it was never my intent to criticize SENS publicly, but rather to foster discussion so that it could be forged into a compelling scientific argument that would challenge scientists to disprove it - and having tried to do so and failed - then be motivated to conduct the necessary practical research.

#6 jwb1234567890

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Posted 27 February 2005 - 12:49 PM

WILT is primarily a Cancer prevention mechanism... it is not meant as a anti-aging mechanism directly... but it is still required.

As far as I can see, your upping of DNA repair mechanism does nothing about the problem of how to deal with cancer once it has taken hold. WILT on the other hand does deal with this problem. So what is your proposed solution for this as you wish to replace WILT with DNA repair improvement?

And cancer will eventually take hold as no repair mechanism works 100% of the time.

That being said I do believe that increasing dna repair genes (e.g. p66) coupled with hormones replacement therapy could give an extra 5-10 years (of healthy years!)

Jack

#7 jaydfox

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Posted 27 February 2005 - 04:08 PM

As far as I can see, your upping of DNA repair mechanism does nothing about the problem of how to deal with cancer once it has taken hold. WILT on the other hand does deal with this problem. So what is your proposed solution for this as you wish to replace WILT with DNA repair improvement?

And cancer will eventually take hold as no repair mechanism works 100% of the time.

It's not like WILT would cure cancer so efficiently as to obviate the need to repair DNA altogether. Cancers will still form. And between the ALT method of telomere extension, and cancers' ability to subvert otherwise healthy cells (complete with intact telomeres), cancer will still require treatment at the doctor's office. It's not like WILT is going to turn cancer into a common cold, an annoyance that goes away on its own.

So if we're not going to be able to stop all cancers, then we have to start getting practical. If WILT could even cure 99% of cancers (which I doubt), and DNA repair could prevent 80% of cancers, then either way, we're looking at a greatly reduced work load on the cancer treatment centers. But with WILT, those resources will still be strained because of all the extra staff to perform reseedings (a procedure which itself will be dangerous and have a fairly high risk of death). And to top it all off, you're programming death into people.

All of which means that DNA repair at least merits serious consideration, not just within the scientific community (which is what everyone here is proposing when they suggest we go publish rather than consider the problem themselves), but within the sub-community that supports SENS (e.g. ImmINst, the presenters at SENS2 and their colleagues, and especially Dr. de Grey himself).

DNA repair doesn't have to replace WILT, as I've said before, but they are complementary. You can do one or the other or both. If DNA repair is sufficient that we don't need WILT, then great, we can feel better about ourselves that we didn't resort to programming everyone to die so that they could live longer. If, after 25 years of our best efforts, DNA repair is not sufficient to achieve a high enough life extension relative to the high costs of WILT, then we throw WILT into the system as well.

But if DNA repair isn't even considered, and then 25 years from now it's acknowledged that we didn't have to program humanity's death just to effect a few extra decades, then we're going to feel ashamed.

#8 jwb1234567890

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Posted 28 February 2005 - 09:59 AM

Well the initiator of this thread thinks that DNA repair mechanism is a replacement for WILT. I believe that there is enough money already going into DNA repair work so its not so important to focus on it and get more funding.

Actually I would say that WILT would cure cancer so efficiently even with our current level of dna repair. While increasing dna repair wont.

And you say that reseeding will carry significant risk but then so does gene therapy currently (the definition of irony: putting in a dna repair gene that gives you cancer). We are both presuming that these technologies get to the point that they are routine and relatively risk free.

Also you say this like there is no research being done on dna repair.. when there is a plethora of research and journals dedicated to this one topic, but how much is focussed on making WILT a reality?

And it seems like you had no answer for what to do once cancer gets hold... in the WILT world you have a set procedure, in your dna repair world the horse has bolted and your done for. So tell me what do you do in this scenario?? get chemo?? oops more dna damage.

I am sure that the SENS supporting sub-community has considered DNA repair after all this idea has been around for over 40 years. It is just not the long term solution to fix the cancer problem.

Your already programmed for death... try going more than a week without water and see how far you get. We already have things we rely on eating, sleeping shelter, doctors visits... to keep us healthy why do you have a problem with adding in one more procedure that has to be done every 10 years? if your serious about doing any sort of rejuvenation then you have to realise that pratically it would mean doing some sort of overhaul procedure every so often just like servicing your car:)

Jack

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Posted 28 February 2005 - 02:44 PM

Even if WILT were to work precisely as hypothesized - which is a great stretch - then it can only address telomerase limited cancers, Jack. There are other cancers that can preferentially proliferate and cancers being the crazy adaptive cells they are, may figure out a means whereby they can maintain their telomeres using a different strategy. The other problem with WILT is that dealing a death sentence to stem cells means they have to be replenished very often. How often exactly remains to be seen - Aubrey came up with 10 years whilst research from other scientists suggests that it may be as often as 3 months. You mentioned the dangers of gene therapy which of course are the same whether we use gene therapy to implement WILT or better DNA repair so that's not an argument against DNA repair.

You're very wrong on one point, Jack. The SENS people have not seriously considered enhancing DNA repair - they don't think it will make much of a difference, because between WILT and allotopic expression they think they have it all figured out - which is wrong because the data they are basing their ideas on is very likely to be wrong and that is what these debates are all about - looking at alternatives with a better chance at success.

It would be great to have both options wouldn't it? I know which one I would use and which one I would allow my child to use. I don't see people hesitating to get their DNA repair enhanced, but disabling stem cells? That's pretty scary. So tell me Jack, would you undertake a procedure that sentences your stem cells to death? And if you did, what is the most often you would tolerate undertaking the reseeding procedure?

#10 jaydfox

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Posted 28 February 2005 - 04:30 PM

In an ideal world, there would be several routes to achieving an ageless or practically ageless state (e.g. periodic rejuvenation, as opposed to truly continuous agelessness). Some methods would be biological (gene therapy, stem cell procedures, etc.), some would be pharmacological, some would involve nanotech, and some would be hybrids.

We're not in that world, so for now, we have to settle for what we can get. But we shouldn't settle too much. If viable options are on the table, and they are complementary with the currently considered options (i.e. we can do one, or the other, or both), and if they can be researched rapidly in cost effective organisms, and if they fill a vital practical role, they should be considered.

What vital practical role? Well, there are a couple. First, enhanced DNA repair can make WILT a somewhat more practical procedure, by decreasing the required frequency of reseedings. Second, in the younger generations who are not already at high risk for cancer, WILT wouldn't even be necessary, as they could "bootstrap" with enhanced DNA repair and await the next therapeutic technique to come along after WILT, thus avoiding those few critical decades when our technology has to resort to programming death to save people. I'm not really against people in their 70's (and maybe even 60's) and up getting WILT, but for people in their 40's and under who simply want to bootstrap their way to escape velocity, WILT is a horrible plan. Which is why we must have the other option on the table. People in their 30's and 40's (and probably 50's, if their health is good) aren't going to want WILT, and waiting until people are in their 60's or 70's before they can get DNA protection (even if it only leads to cancer, which I disagree with), exposes those people to unnecessary risk, and makes the job of later rejuvenation much broader.

#11 jwb1234567890

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Posted 28 February 2005 - 09:29 PM

>Quoted from prometheus

Can you answer the question of what you would do when cancer does take hold of you?
And it will happen the DNA repair will never be 100% efficient as you still have mutation occuring
in the form of DNA deletions.

>Even if WILT were to work precisely as hypothesized - which is a great stretch - then it
>can only address telomerase limited cancers, Jack. There are other cancers that can
>preferentially proliferate and cancers being the crazy adaptive cells they are, may figure
>out a means whereby they can maintain their telomeres using a different strategy.

Well of course there is the ALT pathway I include this in with telomerase. But they are hardly likely
to mutate a whole knew gene if you take it out and there aren't any close homologs or domains. This is my conjecture
but so is your we can upregulate DNA repair genes and there will no unforseen consequences.

>The other problem with WILT is that dealing a death sentence to stem cells means they have to be
>replenished very often. How often exactly remains to be seen - Aubrey came up with 10 years
>whilst research from other scientists suggests that it may be as often as 3 months. You

Nice phrasing here to make it seem that Aubrey made it up whilst your other more reputable
scientists discovered it for a fact.

>mentioned the dangers of gene therapy which of course are the same whether we use gene
>therapy to implement WILT or better DNA repair so that's not an argument against DNA
>repair.

It was an argument against Jay saying that the reason we shouldn't do it is because it will
have a unacceptably high mortality rate (for the reseeding) which he bases on current technology.

>You're very wrong on one point, Jack. The SENS people have not seriously considered
>enhancing DNA repair - they don't think it will make much of a difference, because between
>WILT and allotopic expression they think they have it all figured out - which is wrong
>because the data they are basing their ideas on is very likely to be wrong and that is what
>these debates are all about - looking at alternatives with a better chance at success.

I disagree with this, at the very least they have read through your many many many posts on
this subject and responded. I think the main problem you have here is that they don't agree with you.

>It would be great to have both options wouldn't it? I know which one I would use and which
>one I would allow my child to use. I don't see people hesitating to get their DNA repair
>enhanced, but disabling stem cells? That's pretty scary. So tell me Jack, would you

and gene therapy is not scary?? what planet do you live on.

>undertake a procedure that sentences your stem cells to death? And if you did, what is the
>most often you would tolerate undertaking the reseeding procedure?

Lets see if its a choice between one procedure I do every 10 years which guarantees me no
cancer or gene therapy which guarantees me to get cancer on average 1% every year I know
which one I would take.

But of course I take your point that if it were a much smaller timeline then the strategy would have
to be altered.

But people still do scary procedures as long as they like the outcome... lets see liposuction... involves
a doctor basically poking a metal rod in you and swishing it around then sucking out all the fat.
Sounds pretty scary but people do it and only to look good.

Sorry for the poor formatting.
Jack

#12 Cyto

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Posted 28 February 2005 - 09:37 PM

I find Harold’s side appealing, not as the complete route of dedication (I know this isn't stated as such), but a rather valid preventative role to be investigated in application for humans. While DNA Repair, in all its pathways tropisms, does have a lot of research expanding the basic biological understanding - so does cancer. I do agree with quite a bit of SENS but I think that other avenues for cancer prevention and ablation are present [Attachment]. Not in the manner that they themselves don't need further improvement but rather my difference lies in preference of therapy functionality and information on currently working models. Of course that view applies to more than just the Cancer issues.

It looks that everyone in this field would need a long-term competent culture for engineering and vector targeting competency. The cultures should express longer stability if exo/endogenous damage was mitigated, markedly. As for vector targeting [see next posts attachment] I see this areas advancement allowing for "the sides that will differ on matters" to go about engineering in their own ways.

#13 Cyto

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Posted 28 February 2005 - 09:39 PM

[]

#14 jwb1234567890

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Posted 28 February 2005 - 09:55 PM

>Quoted from jay

>In an ideal world, there would be several routes to achieving an ageless or practically ageless state (e.g. periodic rejuvenation, as opposed to truly >continuous agelessness). Some methods would be biological (gene therapy, stem cell procedures, etc.), some would be pharmacological, some would >involve nanotech, and some would be hybrids.

Sounds good:)

>We're not in that world, so for now, we have to settle for what we can get. But we shouldn't settle too much. If viable options are on the table, and they are >complementary with the currently considered options (i.e. we can do one, or the other, or both), and if they can be researched rapidly in cost effective >organisms, and if they fill a vital practical role, they should be considered.

There is no question on this, the research is taking place as I stated before much more money goes into DNA repair than WILT.

>What vital practical role? Well, there are a couple. First, enhanced DNA repair can make WILT a somewhat more practical procedure, by decreasing the >required frequency of reseedings.

how is frequency of reseeding connected to DNA repair? as far as I am aware we don't even know enough about stem cells to make that assumption.

>Second, in the younger generations who are not already at high risk for cancer, WILT wouldn't even be necessary, as they could "bootstrap" with enhanced >DNA repair and await the next therapeutic technique to come along after WILT, thus avoiding those few critical decades when our technology has to resort >to programming death to save people.

Thats the thing WILT is the solution to the cancer... its not a bootstrap and then hope something else comes along.

>I'm not really against people in their 70's (and maybe even 60's) and up getting WILT, but for people in their 40's and under who simply want to bootstrap >their way to escape velocity, WILT is a horrible plan. Which is why we must have the other option on the table. People in their 30's and 40's (and >probably 50's, if their health is good) aren't going to want WILT, and waiting until people are in their 60's or 70's before they can get DNA protection (even >if it only leads to cancer, which I disagree with), exposes those people to unnecessary risk, and makes the job of later rejuvenation much broader.

Any therapy that is not mature enough is not advisable (would you like to be the first to try out your new DNA repair gene enhancement?)

Why do you have to include your ideas in SENS? Can you not work on it separately? There is nothing stopping you thinking up your own ideas and promoting them to the scientific community as Aubrey does. If you think his ideas are so bad then promote your own and see how far you get.

If you idea has merit then it shouldn't have to ride on someone elses coat tails.

Jack

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Posted 28 February 2005 - 11:46 PM

If you idea has merit then it shouldn't have to ride on someone elses coat tails.


My dear chap, if others coat tails could not be ridden on we would still be in the stone age and I would be making you my dinner!

It sounds like you passionately believe in what SENS promises so the next step for you may be to learn about whether it can deliver! Do yourself the kindness to read some biology on cancer, as so many others here with limited biology backgrounds have done, so that at the very least you understand its fundamentals and how much of a role telomerase plays. Then your input and challenges will be welcome. Otherwise if you choose to believe in it blindly - which is your prerogative - then be good enough not to attempt to challenge the alternatives proposed because you risk sounding more like a religious fanatic.

#16 jwb1234567890

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Posted 01 March 2005 - 09:36 AM

If you idea has merit then it shouldn't have to ride on someone elses coat tails.


My dear chap, if others coat tails could not be ridden on we would still be in the stone age and I would be making you my dinner!

It sounds like you passionately believe in what SENS promises so the next step for you may be to learn about whether it can deliver! Do yourself the kindness to read some biology on cancer, as so many others here with limited biology backgrounds have done, so that at the very least you understand its fundamentals and how much of a role telomerase plays. Then your input and challenges will be welcome. Otherwise if you choose to believe in it blindly - which is your prerogative - then be good enough not to attempt to challenge the alternatives proposed because you risk sounding more like a religious fanatic.


If anyone is a religious fanatic it is you, worshiping at the altar that is dna repair day in day out, anyone who disagrees with you must be blind to the true way.

If an idea has merit then it should be able to stand on its own legs.

I don't follow it blindly I have informed myself thanks and I am studying biology thanks.

What you would do when cancer does take hold of you? (third time of asking)

#17

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Posted 01 March 2005 - 04:09 PM

If cancer were to take hold of me at present then I am afraid I would see my oncologist! Both SENS and neoSENS are completely theoretical. But if they were available today SENS, via WILT would be no help since it is designed to prevent cancer and not cure it. I did propose elsewhere in these forums a treatment deliverable using gene therapy technology and which works like this: a gene is introduced systemically that encodes a cell suicide gene under the control of a promoter which responds specifically to proteins produced in the type of cancer that is diagnosed.

Anyway, my intention was not to offend you. We are all in this together. But do try to learn as much as you can (and tell me why you think DNA repair cannot stand on its own legs). ;)

#18 jwb1234567890

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Posted 02 March 2005 - 10:23 AM

If cancer were to take hold of me at present then I am afraid I would see my oncologist! Both SENS and neoSENS are completely theoretical. But if they were available today SENS, via WILT would be no help since it is designed to prevent cancer and not cure it. I did propose elsewhere in these forums a treatment deliverable using gene therapy technology and which works like this: a gene is introduced systemically that encodes a cell suicide gene under the control of a promoter which responds specifically to proteins produced in the type of cancer that is diagnosed.

Anyway, my intention was not to offend you. We are all in this together. But do try to learn as much as you can (and tell me why you think DNA repair cannot stand on its own legs). ;)


Utimately I believe your DNA repair tweaking would decrease your likelyhood of getting cancer
but it doesn't help once you get it. Relying on the oncologist is not exactly the best strategy for
the future.
While with the WILT proposal (with all the assumptions this entails) you will not get cancer.

Thats why I don't see your solution as a replacement, on its own it is incomplete. Even if you think that WILT is the wrong solution yours is still incomplete.

You spend much time trying to incorporate your ideas into SENS... would it not be better to form an alternative to it. After all SENS was pretty much dreamt up and is promoted mainly by Aubrey. You could do the same... rather than just doing a wiki page about it... a whole web site on exactly the solution you envisage. Then that gives you an anchor to build on. Then you go about the task of:
A) raising cash for your ideas
B) join the dna repair conferences and societies there are to meet with researchers in this field to get them interested in your ideas.
C) write up a grant proposal and do it yourself.
D) move public sentiment to an anti-aging stance rather than the current pro-aging stance it is at.
E) Set up a biotech get some VC funding for a profitable proposal.

When I mean profitable I mean; The key to all this is making your proposal relevant to todays world... pick a disease any disease.. how will your solution make it better... (forget about the aging aspect for a second). How about a DNA repair upping after someone has just done chemo to improve recovery and reduce the chance of relapse, you would have people beating down your door for that one. You win as it advances your research goals and it goes into human trials also it has the potential to be profitable so you are more free to do exactly the kind of research you envisage.

I don't mean to sound like I think this would be easy, me personally I am concentrating on A) and trying to do a bit of D) But ultimately its about doing E) the whole chain from biotech to healthcare... from cradle to no grave.

Maybe you are already doing all this but from where I stand I have no visibility of it and all I see is detrimental SENS bashing.

Jack

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Posted 02 March 2005 - 11:37 AM

I agree, that it can appear detrimental, Jack. My intention is to catalyze thinking because I am eager for scientists to start working on solutions rather than tinkering with mutations and observing phenotypes. There is already so much data out there that reasonably solid theoretical frameworks can be constructed to entice the research community to devote resources for prospective intervention studies. My intention is not to create a SENS competitor through neoSENS, but to compel Aubrey to consider the influence of nuclear DNA damage on aging and incorporate it as SENS target - but not via WILT - which is a cancer preventative and does not acknowledge or address the role of nuclear DNA damage in aging. Despite numerous exchanges in these forums he has not remotely convinced me that nuclear DNA damage is not a key player in aging. But SENS is a monumental idea and needs all the support we can give it which is why I prefer to engage our own community in these discussions rather than appear to criticize publicly.

#20 jaydfox

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Posted 02 March 2005 - 06:55 PM

While with the WILT proposal (with all the assumptions this entails) you will not get cancer.

(my emphasis)

Probably only true of tissues with high division rate (i.e. tissues that will exhaust their 50 division limit in a short time frame). This would be the tissues most necessitative of reseeding, e.g. blood, skin, and gut cells. So, WILT will probably cure leukemia, melanoma, ulcers, and colon cancers, etc. However, for internal organs, muscles, and especially the heart and brain, WILT won't prevent cancers, because those tissues don't exhaust the 50-division limit in a normal lifetime, let alone 10 years.

Whether WILT prevents those cancers that do still form from being fatal is still an open question, though there are a lot of reasons to believe it won't, (and one main reason to believe it will: faith).

#21 jwb1234567890

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Posted 03 March 2005 - 02:49 PM

(my emphasis)

Probably only true of tissues with high division rate (i.e. tissues that will exhaust their 50 division limit in a short time frame). This would be the tissues most necessitative of reseeding, e.g. blood, skin, and gut cells. So, WILT will probably cure leukemia, melanoma, ulcers, and colon cancers, etc. However, for internal organs, muscles, and especially the heart and brain, WILT won't prevent cancers, because those tissues don't exhaust the 50-division limit in a normal lifetime, let alone 10 years.

Whether WILT prevents those cancers that do still form from being fatal is still an open question, though there are a lot of reasons to believe it won't, (and one main reason to believe it will: faith).


I think you are not factoring into account the amount of the division the cancer cells requires to become dangerous.

Also tell me why would all cancers bother expressing telomerase or ALT if they did not require it?

Jack

#22 jwb1234567890

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Posted 03 March 2005 - 03:33 PM

I agree, that it can appear detrimental, Jack. My intention is to catalyze thinking because I am eager for scientists to start working on solutions rather than tinkering with mutations and observing phenotypes. There is already so much data out there that reasonably solid theoretical frameworks can be constructed to entice the research community to devote resources for prospective intervention studies. My intention is not to create a SENS competitor through neoSENS, but to compel Aubrey to consider the influence of nuclear DNA damage on aging and incorporate it as SENS target - but not via WILT - which is a cancer preventative and does not acknowledge or address the role of nuclear DNA damage in aging. Despite numerous exchanges in these forums he has not remotely convinced me that nuclear DNA damage is not a key player in aging. But SENS is a monumental idea and needs all the support we can give it which is why I prefer to engage our own community in these discussions rather than appear to criticize publicly.


SENS does acknowledge that dna damage has a role in aging... it just says its so not important. Obviously if we have the dna repair genes of a mouse we wouldn't get very far. Also fixing the the mitochondrial problem would go along way to obviating much of the dna damage and this is covered already.

People are already working on solutions, you have posted mainy links for this type of research so I am baffled why you believe no one is working on it.

If you truely care about changing SENS then why don't you go to the conference in Cambridge this September and have it out once and for all rather than this protracted reasoned rant?

Also the main driver of SENS is the stunning coverage Aubrey gets by doing all his talks and his constant pushing of gerentologist to look into this kind of research. There is nothing to stop you doing the same. What happened to the paper you talked about authoring?

Also I would be interested to know what role do you see yourself? Active scientist or fund raiser or something else?

This is a public forum, and I am sure journos do check it out.. so if you really cared about this you would write emails or talk in person.

Jack SENStranced and loving it

#23 DJS

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Posted 03 March 2005 - 08:31 PM

Personally, I value Prometheus' contributions here at ImmInst and I hope that he continues his critique of SENS. He makes strong arguments and I doubt that Dr. de Grey is anything but grateful for being kept on his toes.

protracted reasoned rant


your dialog comes off as rather hostile.... [glasses]

#24 jaydfox

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Posted 03 March 2005 - 08:46 PM

If Prometheus and I come off as ranting, it is only because of our relative youth and pride. But let that not detract from the content (and given my limited biology background, my content is probably not of the same quality as Prometheus's content, even if I've matched his quantity of critique). de Grey addresses the content, not the rants, and for that he gets bonus points for his patience, but that patience doesn't add to his content.

It's about the content people, not the emotions. If you're bothered by what appears to be the rant of religious fanatics, tough. de Grey may be better at remaining cool and collected, but I attribute this to his experience and vision more than to the fact that he's right and I'm wrong.

It was a hard lesson for me to learn, as my passionate "rants" were ignored or driven into the ground for lack of merit, and it is only by learning to appeal to reason and logic that I've tried to prevent this discussion from becoming counterproductive. I still fumble, and I still let my passion obscure the points I'm trying to make, but that doesn't mean my points are invalid.

#25

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Posted 03 March 2005 - 10:39 PM

If you truely care about changing SENS then why don't you go to the conference in Cambridge this September and have it out once and for all rather than this protracted reasoned rant?



Have what out? No man can stand against those methuselan bristles - he wins! ;)
Seriously, SENS and its DNA repair centric variant neoSENS are, as I have previously said, entirely hypothetical. One may interpret the literature in ways that provide support for either hypothesis - a read of the debate is proof - which is why I suggested an experiment which could help determine the role of the nucleus in influencing mtDNA damage. The SENS core philosophy, however, appears to be driven by the engineering of solutions with less emphasis on a requirement to understand the underlying mechanisms. As I said, before, that's a fine approach so long as the informational landscape is not changing - and so long as the map used is reasonably accurate. Constructing such a map means taking into account all relevant information at hand. But the word relevant can be very subjective. Which brings us back to your fine suggestion which is to attend the SENS conference. Is this a formal invitation? Should Jay and I be getting ready for London's bleak skies?

I think the challenge offered by Reason and Kevin to publish some of the ideas behind neoSENS is a sensible one. There is sufficient information to construct the necessary framework to support the central hypothesis. Once published, the natural evolution would be to present those findings and discuss them with interested parties. If this can be accomplished prior to September, and if we are formally invited, we would be delighted to attend and present.

#26 jaydfox

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Posted 03 March 2005 - 10:57 PM

Once published, the natural evolution would be to present those findings and discuss them with interested parties. If this can be accomplished prior to September, and if we are formally invited, we would be delighted to attend and present.

Six months. A tight deadline indeed. Worse yet, abstract submission deadlines are June 15th.

I've read two dozen papers in the last two weeks, and I have a stack of about six or eight dozen more to go through, and a wishlist of yet another few dozen. I can read all those papers in the next two to three months, but publishing, nay, submitting for publishing the papers in time to reach the September deadline, let alone the June deadline, is a steep challenge.

Which brings us back to your fine suggestion which is to attend the SENS conference. Is this a formal invitation? Should Jay and I be getting ready for London's bleak skies?

Well, looking at the abstract submission form, I see that we can apply as Invited, Oral, and Poster. Since we're not invited, and not likely to be without being published, that would leave oral and poster. Oral spots are limited, and I assume predicated on being published. What is "Poster"? Just a full-color poster in the foyer?

Given the travel expense, I don't think I'd attend unless Harold (or I [lol] ... [mellow] ) were presenting.

#27 ag24

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Posted 03 March 2005 - 11:53 PM

For Jay and others unfamiliar with the conventions of conferences:

Anyone, regardless of affiliation or publication record, can submit an abstract at the website. The abstract is a short (~200-word) description of the work that will be presented. This work does not need to be experimental -- theoretical work is admissible too. Out of the submitted abstracts, a number are chosen for oral presentation (in slots half the length of the invited talks). Those that are not chosen for this are displayed as posters, which means the presenter gets a space roughly four feet square to use as they wish to present the work. In 2003 there were about 80 posters -- i.e., more than there were talks (invited plus submitted combined). Posters are not a second-rate way to present one's work: everyone starts by presenting that way. This is demonstrated by the fact that there are periods set aside in the meeting as "poster sessions" -- tiimes when the delegates wander around reading the posters and talking to the authors. Typically each poster presenter is assigned a specific hour when they are asked to be near their poster so that everyone else (except those doing it at the same time - this is a well-known unsolved problem in science) can ask them questions. Poster presenters also get to publish their work in the proceedings volume (submission deadline: the date of the meeting), just like invited and oral presenters.

The above is an entirely generic conference format - the SENS meetings are not unusual in this regard. (What is distinctive about the SENS conference posters is that they are set up in the conservatory that is an annexe to the bar, the poster sessions are after dinner, and all drinks are free during poster sessions. That tends to make for good attendance...)

#28

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Posted 04 March 2005 - 07:34 AM

Sounds terrific .. especially the proximity to the bar. (Good God - English Ale! ) [lol]
On the other hand I would like to get these notions of ours published before any such forays.

#29 ag24

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Posted 04 March 2005 - 11:35 AM

One other thing I should perhaps have emphasised is that it is customary to present **unpublished** work at conferences. Conferences focused mainly on published work are not so obviously worth the registration fee.

#30 jwb1234567890

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Posted 04 March 2005 - 05:48 PM

Personally, I value Prometheus' contributions here at ImmInst and I hope that he continues his critique of SENS.  He makes strong arguments and I doubt that Dr. de Grey is anything but grateful for being kept on his toes.



your dialog comes off as rather hostile....  [glasses]


I also value Proms contributions.. I forwarded on one of his threads to a Phd doing aging research (which in hindsight was a mistake as many gerontologists see the word immortal and run a mile)

This thread is a hostile one check out the title, I am trying to keep to the theme;)

And he does rant and generally they are reasonable.

I used to live in Lyndhurst briefly about 4 years ago, hows the neighbourhood doing?

Jack




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