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Revisiting the need for evolving SENS


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#1

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Posted 28 May 2006 - 04:48 AM


I'm sure that many of you are eagerly awaiting the publication of Technology Review's "SENS Challenge" article. If you are expecting Aubrey to deconstruct his detractors' arguments in typical style then you will not be disappointed. Neither will you discover that his critics have revealed any new dimensions of biology that undermine SENS. Same old, same old as they say.. And another glorious victory for SENS and its supporters.

Since those criticisms and rebuttals were written (and will shortly be published) however, some interesting studies have been reported that stand to obliterate one of the pillars on which SENS is founded:

1. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7753-8.
Transferable anticancer innate immunity in spontaneous regression/complete resistance mice.
Hicks AM, Riedlinger G, Willingham MC, Alexander-Miller MA, Von Kap-Herr C, Pettenati MJ, Sanders AM, Weir HM, Du W, Kim J, Simpson AJ, Old LJ, Cui Z.

2. Hum Mol Genet. 2006 Jun 1;15(11):1757-68.
Mitochondrial localization of telomerase as a determinant for hydrogen peroxide-induced mitochondrial DNA damage and apoptosis.
Santos JH, Meyer JN, Van Houten B.

The first article reports on a strain of mouse that is completely resistant to cancer and from whom cancer resistance is transferable by a process as simple as a blood transfusion. The second article reports on the discovery that telomerase acts as a stem cell quality control mechanism - in its absence a stem cell's genome would become increasingly vulnerable to propagating cancer causing mutations.

Also of note is another recent study:

3. Curr Biol. 2006 May 23;16(10):R359-60.
Gene expression becomes heterogeneous with age.
Somel M, Khaitovich P, Bahn S, Paabo S, Lachmann M.

Here we see evidence that as aging progresses a decrease in specific expression of genes occurs. In effect cells slowly lose their identity as they become more random in their gene expression. The consequences are a loss of tissue/organ function and increased risk of cancer. Such stochastic changes in gene expression could well be a result of accumulation of nuclear DNA (nDNA) damage due to insufficient repair and maintenance mechanisms.

For those familiar with SENS they would immediately recognise the implication for WILT - the SENS approach of dealing with cancer - as being made both redundant (1) and dangerous (2) by these findings. This is no cause for alarm though, since these findings also promise that innate immunity can deal with cancer and that telomerase can once more be considered as a safe means of extending functional cell lifespan. The third study mentioned underlines that nDNA damage can play a greater role than just increasing the risk of cancer but also contributes to tissue/organ dysfunction.


What do these studies tell us? Firstly, that it is time to critically re-examine the usefullness of WILT in the SENS collective and secondly to consider that nDNA damage contributes more to aging than cancer and therefore requires to be addressed as such.

#2 maestro949

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Posted 28 May 2006 - 05:39 PM

Lots of good info prometheus, particularly on the cancer front though the deteriorating gene expression finds seem to be an even more important as it points to a potential root cause of cancer and other maladies that are results of senescence and validates the idea that most cancers are a symptom of aging - young people rarely get cancer.

#3 reason

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Posted 28 May 2006 - 05:48 PM

The best way to evolve SENS is to get more money behind SENS research. If the research is moving rapidly, and thus the science changing rapidly, SENS will naturally evolve more towards its blanket philosophy/statement of goals side and away from specific scientific position side.

#4 eternaltraveler

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Posted 28 May 2006 - 08:24 PM

Since those criticisms and rebuttals were written (and will shortly be published) however, some interesting studies have been reported that stand to obliterate one of the pillars on which SENS is founded:


I found those articles very interesting myself. However if someone tried to win the SENS challenge by showing that SENS isn't the best way to accomplish dramatic life extension, that there is instead a better way, that would be even a greater victory for us than Aubrey simply winning the challenge, because it would force the admission that radical life extension is not only possible, but very foreseeable.

#5

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Posted 28 May 2006 - 10:23 PM

I found those articles very interesting myself. However if someone tried to win the SENS challenge by showing that SENS isn't the best way to accomplish dramatic life extension, that there is instead a better way, that would be even a greater victory for us than Aubrey simply winning the challenge, because it would force the admission that radical life extension is not only possible, but very foreseeable.


Indeed. Perhaps Aubrey is too accomplished at defending the theoretical basis of his work, to the degree that genuine opportunties for improvement may be excluded.

The best way to evolve SENS is to get more money behind SENS research.


No doubt, but to clarify my point: even theories are not cast in stone and are subject to improvement -- at this stage SENS remains a hypothesis.

#6 Lazarus Long

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Posted 30 May 2006 - 05:38 AM

There is also the idea of covering all your bases. This article is illuminating for more than what it says, it also demonstrates that the meme is becoming mainstreamed quite effectively and then a demand for funding can follow.

http://www.imminst.o...44

The real question will then be where to best apply those funds and not whether there is enough. It won't be money that ultimately solves these problems it will be people, perhaps people enhanced by computers but people nonetheless.

#7

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Posted 30 May 2006 - 06:15 AM

If the research is moving rapidly, and thus the science changing rapidly, SENS will naturally evolve more towards its blanket philosophy/statement of goals side and away from specific scientific position side.


Until it does evolve into a statement of goals, SENS becomes increasingly at risk of potentially discrediting criticism - particularly as visibility increases. The central principle of SENS is a timeless approach behind most great inventions. Some of the present implementation strategies, however, are becoming long in the tooth and rapidly falling behind what is the state of art in biological knowledge. Admittedly, it is difficult to make changes without it appearing like a victory for its detractors.

#8 maestro949

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Posted 30 May 2006 - 11:00 AM

Admittedly, it is difficult to make changes without it appearing like a victory for its detractors.


Nonetheless its critical to constantly reshape the strategy as new evidence unfolds and I suspect SENS will go through many refinements and generations of evolution over time. Not adapting to new emergent ideas and evidence will certainly plague SENS moreso than making adjustments based on objective and constructive criticism. I look forward to the challenges and criticisms from other scientists as there is no further evidence that an approach has merit than dialogue even if it starts out as "Yes we can" vs. "No you can't." If this dialogue can evolve to the next stage then both sides will need to dive into details and start explaining the "hows" and "whys" which will lead to a refinement of the problem statement and roadmap which can only be a win for longevity research in general.

#9 Live Forever

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Posted 30 May 2006 - 09:50 PM

SENS is (in theory) completely seperate from the M-Prize, correct? It was my understanding that SENS is just one theory competing for the M-Prize, but that could be incorrect.

#10 John Schloendorn

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Posted 31 May 2006 - 01:44 AM

SENS is not currently competing for the Mprize. SENS is designed for humans, the Mprize for... well, you would have guessed. It is unfortunate that mouse and human aging are quite dissimilar. For example, the only SENS research that is currently directly funded by the MF is medical bioremediation. The age-related storage diseases that this paradigm seeks to combat account for up to two thirds of all human deaths in developed countries, but are not normally causes of death in the lab mouse. I feel this lack of synergy is unavoidable and endurable.

In part, the Mprize is designed as a backup if SENS (the IBG approach) should suffer major failures either in terms of technology or sociology.

It has been brought forward by SENS critics that the Mprize might suffer from its administrative association with the (in their view) unproductive other SENS initiatives.




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