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Aubrey's IBG


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#1 John Schloendorn

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Posted 01 January 2005 - 05:18 AM


You sure know about Aubrey's proposal of an Institute of Biomedical Gerontology devoted to the development of engineered negligible senescence . I have made a little survey to asses how much material and human resources we are ready to throw at this type of project at this time. As you may have noticed, the survey is heavily advertised at major transhumanist web sites. In addition, a large selection of biomedical researchers have been invited.

If you think Aubrey's project is any good, do not hesitate to indicate your support here.

I wonder if you can think of any other participant groups that should be invited, such as potential financial supporters. Have any address list of excentric billionaires around? Please post your responses here, rather than contacting such persons directly, to avoid multiple inquiries.

Best wishes, John.

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Posted 01 January 2005 - 11:21 AM

I have one billionaire in mind. His name is Paul Allen.

He has funded the winning team of the X prize, creating the first successful commercial space craft. He has also established the Allen Institute for Brain science to expand our scientific understanding of the brain. I would seriously consider contacting Paul Allen through formal channels of communication and presenting Aubrey's proposal to him. I would rather see one formal, well written request for Mr. Allen's attention, rather than a barrage of informal inquiries which could turn him off immediately to Aubrey's proposal.

Failing that, Richard Branson of Virgin Atlantic may be another excentric billionaire worth contacting. He is planning to establish his Virgin Galactic company using a refined design of Paul Allen's spacecraft to take tourists into space.

#3 John Schloendorn

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Posted 01 January 2005 - 12:40 PM

Hmm, you are right. We should make a seperate project of contacting billionaires in a coordinated way. For a start, how could we solve the excruciating difficulty of getting through to them at all?

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#4 nanodoc

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Posted 01 January 2005 - 07:26 PM

Thats simple. I have a 21 year old daughter who is a model, and absolutely great at communicating. On a small scale, she's talked to others, convincing them of the virtues of nano, or of anything for that matter. She can sell ice to an Eskimo if need be. Send her over to England, and she'll be able to talk to Branson, or Paul for that matter! She's the blonde on the home page of my website.
Ed
www.encinosmiledr.com

#5 reason

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Posted 01 January 2005 - 08:24 PM

Hmm. I would have thought that separate similar proposals from different organizations would have more weight than one proposal made through a coordinating agency.

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

#6 lightowl

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Posted 01 January 2005 - 08:27 PM

Getting wealthy people to see the potential impact of the longevity cause and then ultimately convincing them to contribute their resources ( money and influence ) is one of the most powerful tools we have to achieve longer and healthier lives for everybody. When influential people start contributing, many people will listen to what they have to say about why and how aging interventions can happen. This process is a landslide starter and will eventually ignite by itself when the meme has spread wide enough. We have the power to accelerate this process. The best example, as to my knowledge, is the Methuselah Mouse Prize (MMP). There are multiple wealthy donors to the MMP. Some of which have chosen to remain anonymous. I think one reason for this is that there is still a strong deathist meme that puts a negative spot on all contributors from a public perspective. This spot will weaken as the longevity notion becomes more main stream.

I think it is important to realize that wealthy people don't just give away money to something they don't know anything about. It is up to us to inform them to our best abilities. In addition to concrete unbiased information, a list of non-anonymous prominent supporters would greatly improve the chances of catching their attention. This "Reference List" is a common method for promoting a business. In such case the list would be composed of prominent customers.

I made a quick scan of ImmInst to find a few subjects with relevance to thread:

Why Doesn't Kurzweil Really Donate to the MMP?
http://www.imminst.o...t=ST&f=1&t=4832

ImmInst Contacting John Sperling
http://www.imminst.o...ST&f=142&t=3006

What would you do with three billion dollars?
http://www.imminst.o...ST&f=137&t=3077

Potential funding source for life extension
http://www.imminst.o...ST&f=161&t=4342

Aubrey's IBG
http://www.imminst.o...ST&f=142&t=4979

Imminst fundraising brainstorm
http://www.imminst.o...ST&f=137&t=3076

A prize that surges in value
http://www.imminst.o...ST&f=161&t=4817

The subject has moved here:
Billionaires
http://www.imminst.o...ST&f=142&t=4982

Edited by lightowl, 07 January 2005 - 06:04 AM.


#7 John Schloendorn

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Posted 01 January 2005 - 10:57 PM

Maybe we should move the billionaire thing to a new thread here.

#8 reason

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Posted 02 January 2005 - 12:19 AM

I commented in that other thread - synopsis is that less contacting, more work on the backup materials and community prior to contacting is the best way forward.

Reason
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#9 John Schloendorn

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Posted 03 January 2005 - 09:00 AM

Just a little update:
This is day 3 of the survey. Although no advertisement is in place yet, except this post, we already have:

- 16 participants
- 5 of which would join up, some with a biology background
- Announcements of over $30.000 donations instant cash from different participants
- Announcements of much more money when the institute is in place and successful

Not too bad for the first three days I reckon. Preparations to invite a large number of aging researchers are running hot.

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#10 John Schloendorn

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Posted 04 January 2005 - 02:28 PM

For a pasttime while the survey is running, enjoy an entirely imaginary story:

It is summer 2005. During the analysis of the survey data we came across a strange entry by a participant who used a pseudonym and promised $1 billion instant cash plus another $2 billion over the course of 10 years to fund the IBG. Just to see what happens next, Aubrey wrote him an e-mail. In the course of the negotiations that followed, we were able to confirm that the person in question is a high government official of a middle eastern developing country named Nediria. The Nedirian regime came to power during a series of civil wars in the 1980s, after the Soviets gave up their occupaton of the country. Human rights have never existed in Nediria and the only laws that do exist are a particularly bloody interpretation of the Sharia, which is, however, only enforced when it serves the interests of the government. The Nedirian dictator is known for megalomania, comparing himself to Hitler, commiting haphazard mass arrests and endorsing torture. Basically, the only reason he is still in power is that Nediria does not have much oil.

The point is, they mean it. The entire government elite of Nediria grew fond of the Idea that living forever would be a nice thing to do and they are ready to squeeze the last cent out of their country in order to make it real. We do not even have to locate the institute within Nediria. All they want is to be among the first that will enjoy any anti-aging interventions we develop, but they do not ask for the exclusive right to do so. As it turns out, one Nedirian government official had already made a substantial contribution to the Methuselah Prize in early 2005, when his occupation had not been discovered.

What do you think happens next?

#11 John Schloendorn

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Posted 07 January 2005 - 01:51 AM

Nobody's got time for a pasttime, do you? [thumb]

#12 lightowl

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Posted 07 January 2005 - 11:49 AM

Survey mentioned in KurzweilAI newsletter.

*************************
Survey to guide fundraising
strategies for human-aging research
KurzweilAI.net Jan. 7, 2005
*************************
A survey to guide fundraising
strategies for the Methuselah
Foundation and the future Institute
of Biomedical Gerontology is
currently being conducted. The
Institute of Biomedical Gerontology,
as envisioned by biogerontologist
Dr. Aubrey de Grey of Cambridge
University, is a "Manhattan Project"
dedicated to finding a true cure for
human aging...
http://www.kurzweila...ID=4128&m=13977



#13 John Schloendorn

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Posted 08 January 2005 - 04:56 AM

Yes, the Kurzweil people were very cooperative. That bunch of computer nerds and heartfelt immortalists sure make powerful allies. Kurzweil people, if you can read this, thanks guys for your support!

Edited by John Schloendorn, 08 January 2005 - 06:48 AM.


#14 treonsverdery

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Posted 08 January 2005 - 11:06 PM

The blonde thing works well Just looking at her I think she must have wonderful mitochondia This might work:
Ive read that there are persons paying to be cloned or to arrive at that I think those people aren't just motivated to have a fraternal twin I think they have immortalist urges
Your daughter might advertise that Italian cloning doctors practical research I read something about wealthy middle eastern n asian cloning clients Your daughters part: progenitor tissue that becomes oocytes. thats right they put their nucleus with her egg
models arrange their bodies to look attractive, while the cloning clients are having a look she tucks her head near her chest then says

You know if I grew a whole new body then just tucked my head full of ideas just like this that the nerves communicated n grew together Id be beautiful clever n immortal just like you Ms gulbenkian

The blonde might then rapidly bring up the physicians Christopher Reeve grant then say

You know if you want to be immortal just fund Chris Reeve grant plus Aubreys IBG Your new body will be just the right size to be a young immortal

Treon I percieve Aubrey thinking at high volume :support the IBG

#15 Karomesis

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Posted 09 January 2005 - 01:28 AM

I find the monetary limitations extremely frustrating. [ang] I have attempted to conjure up publicity ideas for the cause. One of them is using large SUV's and having them embossed with various websites worthy of mention all over, including this one. Any criticisms are gladly welcomed, as I plan on implementing this lunacy in the near future. [thumb]

#16 treonsverdery

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Posted 09 January 2005 - 02:09 AM

Altoids liners fine NLP reread item numerous times wide area reach

Edited by treonsverdery, 09 January 2005 - 03:54 AM.


#17 benzealley

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Posted 18 January 2005 - 04:32 PM

For a pasttime while the survey is running, enjoy an entirely imaginary story:

...

What do you think happens next?


*hops onto a nearby troll to get his head up high enough to be visible*

That was interesting...

I think nobody bites, because even if the offer can be trusted, $1bn isn't enough to get the effort completed and realistically, being associated with any such group would cripple the immortalist political stance too badly in the longer term to be worth the trade-off.

On the other hand, were the offer two orders of magnitude greater, I think we'd be morally obliged to go for it. Realistically, the impact in terms of suffering of your Nedirian rulers surviving somewhat longer is likely to be trivial compared to the gain for the whole species.

And besides, Bush Jr. Jr. or Bush Jr. Jr. Jr. would no doubt get to them eventually... ;)

--
Ben
"There are risks and costs to a program of action. But they are far less than the long-range risks and costs of comfortable inaction."
- John F. Kennedy

#18 eternaltraveler

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Posted 18 January 2005 - 05:58 PM

Questions:

Can we get any of Aubrey's IBG to be funded by California's stem cell money?

Why don't we start going after potentially cooperative governments? Singapore, Japan, China, Korea? Many others.

I think the trick here is to find out whoever these countries scientific advisers are and convince them. Not nearly so hard as contacting billionaires but potentially with the same kind of influence. Contacting scientists in general is not difficult. I know when I see a scientist on the news for some new breakthrough I can actually send them an email and they will respond. It shouldn't be terribly difficult to arrange for someone like Aubrey to meet with them. That’s when the convincing begins.

If we got some country to sponsor this, the IBG would be completely funded in one shot.

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Posted 23 January 2005 - 11:44 PM

The Institute of Biomedical Gerontology, in the way that Aubrey has conceived it, is unlikely to - and does not need to - come into existence.

It is unlikely because it is based on a set of assumptions about the causes of aging and the anti-senescence strategies that emerge based on those causes that the scientific community are not embracing. Namely:
1. Obviating mitochondrial mutations
2. Degrading intracellular junk
3. Preventing and curing cancer
4. Removing unwanted, toxic cells
5. Breaking extracellular crosslinks

Aubrey's strategy for dealing with (1) is convoluted, and in my view unnecessary, if it is considered in the larger context of genomic maintenance and (3) is a relic that belongs in the same category as chemotherapy and radiotherapy. No consideration (or solution) has been provided for nuclear mutations or for the immune disorder problem. Neither have stem cells been mentioned as a solution other than to compensate for the solution for (3). (2), (4) and (5) are valid aging contributors and represent therapeutic goals but are secondary to the issue of genomic mutations, and could be solved in part in whole by a solution to the same.

More importantly, however, the IBG does not need to come into existence. Rather than attempting to raise an enormous amount of funding in order to create a "Manhattan Project" style scientific behemoth - which would rely on the premise that Aubrey's SENS is correct and merely needs the funding and brains to develop the technology - it is a far superior strategy to resource a number of investigative lines of research to explore possibilities in independent labs with the objective being to provide a substantial proof of concept that one or more components of aging can be therapeutically treated.

Edited by prometheus, 24 January 2005 - 03:21 AM.


#20 John Schloendorn

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Posted 24 January 2005 - 01:05 AM

We are currently making a questionnaire to gather a large set of researcher's opinions on how an IBG should be designed, that is including what is a SENS and what not. (This was Aubrey's initiative)
Personally, I strongly favor the use of cellular replacement in some form to solve nearly any problem of aging. But let's see what the senior researchers' have to say.
As far as I'm concerned, it would certainly be an option to spread much of the IBG's activities to many research groups with a traditional organization, which would be coordinated by a rather small central agency. This may have the advantage that the group leaders could perhaps secure some of the funding they are already receiving.

Btw, you should fix that "does need to" in the top line of your post - will make it easier to get your point ;-)

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Posted 24 January 2005 - 03:30 AM

Thanks for pointing it out John. As you properly interpreted I was questioning the validity of the IBG in its present conceptual incarnation.

I think a good example was the human genome project international collaboration which saw many different labs cooperate to complete a single objective. Of course, their objective was relatively simplistic although time consuming, whilst an anti-senescence intervention would require many different approaches to the problem.

For those willing to read through the lines the take home point is that any such venture needs to be solidly scientifically founded in order to have sufficient credibility to mobilize even the most liberal elements within the scientific community .

#22 jaydfox

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Posted 24 January 2005 - 01:17 PM

If I may... Another take home point, for those willing to read between the lines, is the need for a stronger emphasis on addressing nuclear DNA repair and/or robustness. In the long term, it doesn't matter how much intracellular junk we clean up if the DNA is intentionally manufacturing that junk in the first place, due to several lifetimes' worth of accumulated damage.

Body-wide DNA transplants will become an option at some point, and in the shorter term, stem cell therapies could replace many affected tissues, so it's probably not 100% necessary to address nuclear DNA damage. Of course, using the same logic, the same could be said of mitochondrial DNA damage, etc.

In any event, slowing that initial rate of damage seems like a good option, if not to obviate the need for periodic "treatments", at least to reduce the needed frequency of such treatments.

Aubrey's plan to move mitochondrial DNA to the nucleus is based on the assumption that it is much safer there, and that it would be too difficult to try to engineer as effective a DNA-robustness scheme in the mitochondrial genome as already exists in the nucleus.

Well, engineering an even more robust DNA-protection scheme within the nucleus might seem equally as challenging. But, to borrow from Dr. de Grey, as he would move the mitochondrial DNA to the nucleus to take advantage of an existing DNA-defense scheme: Is there a better DNA-defense scheme for the nucleus than that which already is in use?

Why yes, there is. Genes related to calorie restriction, and other such pre-existing genes expressed during similar periods of stress, stresses that might otherwise increase DNA damage rates. We don't have to invent a better nuclear anti-oxidant, though some of those certainly seem to be in the pipeline. No, we just need to find the ones that nature has already built, but left unactivated or underutilized for various reasons.

CR-mimetics are currently a big item, so there's no need for us to get involved there, per se. But a more concerted effort to study the relationships among multiple DNA-repair factors and stress-related genes, in an attempt to maximize effectiveness, does not seem to be underway. And here it is that we could make an impact. Notice also that the model organism of choice here doesn't have to necessarily have a lifetime of 3 years.

For those reading between the lines, this is leading to something far less expensive than the billion-dollar IBG to research, and even far less expensive than researching any one of the seven deadly things in mice.

Will this cure aging? No. Will it become one ingredient in an overall anti-aging scheme? Probably. A better-built engine, with regular maintenance, does not require a more expensive motor oil to get more mileage than a shoddy engine. But better oil still improves overall lifetime. No point spending twenty grand on the engine, and then getting cheap on the oil.

Note also that such a project, by its small size, would be easily implementable by ImmInst with its current human resources, and would be good practice for when the time comes to implement the IBG.

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#23 ag24

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Posted 24 January 2005 - 02:46 PM

The IBG outline at my site is in need of considerable improvement, there's no doubt about that. To answer five points on the science and then two on the IBG concept:

- The reason only five of my seven SENS strands feature there is because I viewed the other two (cell replacement and eliminating extracellular junk) as sufficiently mainstream that no further injection of funding is needed. I still have that view.

- My approach to cancer is (as people here probably know) based on the view that no existing or imminent approach will delay cancer deaths by more than 10-20 years.

- My reason for not mentioning other nuclear mutations is that I think they don't matter in anytrhing like a normal lifetime; our DNA repair and maintenance machinery has evolved to be good enough to stop us from dying of cancer before middle age, and the rest of our genes, in which dysfunction has to occur not just in one cell but in a fair proportion of the cells in a tissue in order to be harmful, get a free ride. Jan Vijg has been trying to prove this logic wrong for a decade or more and has so far only provided a lot of evidence that it's correct.

- Intracellular junk, extracellular crosslinks and most types of toxic cells (e.g. excessive visceral fat) are caused by normal metabolic processes, not by mutations.

- Immunosenescence is a combination of having too many cells of some types and too few of others. Thus it is addressed by two of the existing SENS strands. In fact it will probably be best addressed as a side-effect of WILT (my cancer proposal), as all the cells in question (except the thymus itself, which is a straight cellularity problem already seeing success) are white blood cells whose behaviour can be manipulated by genetic changes to blood stem cells which we'll be refreshing every decade.

- The IBG would have an advantage over normal academia in making quick progress in these areas because it would not be beholden to the usual academic career structure. Science would move a lot faster if those who were doing the actual work had many years of labe experience and did not have as their primary goal the securing of their next job in a year or three. The IBG would not be populated by Ph.D. students and postdocs but by senior technicians.

- The reason I support the Methuselah Mouse Prize as well as the IBG is precisely because I recognise that I may be wrong on the science. In an ideal world there would be several IBG's competing for the MMP -- rather like the X Prize.

#24 jaydfox

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Posted 24 January 2005 - 04:09 PM

Nothing like controversy to get good scientists to make better public arguments. :))

As to the idea of several IBG's, this would be the ideal scenario, and probably require at least the estimated $62.5 million ($100 million in my opinion) value for the MMP, or more specifically, the Rejuvenation Prize.

Actually, I was thinking about that Reversal/Rejuvenation Prize thing. The new structure allows us to award the prize far more often, as the old structure (the Reversal Prize) would basically require someone to come up with an intervention that doubles remaining life expectancy. Not quite the the tripling (trebling? Is that a British English thing?) that de Grey is calling for, but nonetheless a big step.

I was thinking also of the idea of small, frequent awards versus a single winner-takes-all award. The current formulation allows us to award small increments on the way to the main goal of tripling remaining lifespan. We've had the issue come up of how to sustain interest upon reaching our goal, and the current system seems like it will succeed to some degree. (Though, to be honest, once that tripling is achieved, further incremental gains, while exciting, will nonetheless seem anticlimactic in mice. At this point, the focus should probably shift to a new prize, perhaps in a longer-lived species like dogs or monkeys or lemurs or something.)

I have an idea, and it's just an idea, but here goes. Actually, it's not even my idea, to be honest, as I think John or someone else here raised the idea as well.

I think we should still have a winner-takes-all threshold. The current record for the rejuvenation Prize is 1356 days, an average of 6 mice in the top decile of a controlled study. As I recall, this represented a 15% increase in late life, started at 19 months, so I'm assuming the mean for the control group was therefore about ((1/1.15)*(1356-19*30))+19*30, or about 1253 days.

Actually, checking the math, I see that the 15% lifespan increase was total lifespan, not just the late-life portion. The late-life increase in lifespan was therefore much higher, on the order of 30% or so, just eyeballing the numbers I can find on the web (43.6 months versus 37.6 months, with and without CR). Good to know, as I thought that 15% sounded a bit low for CR.

Okay, so we're at 30% or so. Getting to 50%, if started at 19 months, would require getting out to something like 1454 days, which would award... What? The website is sketchy on the details. The formula is laid out in detail for the Longevity Prize, but not so for the Rejuvenation Prize.

If the RP is awarded the same way as the LP, then the award in this case would be about 6.7% of the RP fund. In other words, with a $10 million Reversal Prize, only about $670,000 of it would be awarded.

So picture the year 2016. What happens for that incremental gain, from adding 155% to adding 205% late life, which takes us past the tripling threshold? What fraction of our $50 million prize would be awarded? About 16%.

I think what we need is, in addition to the current structure, a winner-takes-all threshold once remaining late-life has been tripled. It doesn't need to be a new prize, as having three would only further spread thin our thin resources. However, perhaps we could award half the prize money in addition to awarding the usual small percentage. Just an idea.

For example, using 19 months as our threshold, and assuming a typical control group's mean of top decile at 38 months, then our threshold would be 76 months, or just over six years. Using a nice round number like 2300 days should suffice. So let's say someone gets up to 1985 days, and then a new study takes it all the way to 2380 days. This new study would only net 16.6% of the prize. But if we first award half the prize, then 16.6% of the remaining money, this study, which passed the "tripling" threshold, would actually net 58.3% of the prize money. If we could get the prize up to $100 million, this would be just about the $62.5 million that has been postulated as necessary.

#25 John Schloendorn

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Posted 25 January 2005 - 12:31 AM

(Aubrey) The reason only five of my seven SENS strands feature there is because I viewed the other two (cell replacement and eliminating extracellular junk) as sufficiently mainstream that no further injection of funding is needed. I still have that view.

Luckily, the development of cell replacement is mainstream. It is its application to anti-aging which is not. Mainstreamers just seek to replace cells damaged by single age-related diseases, most often in genetic mouse models of these diseases, which is good, but eventually not good enough. I would like to see all these single efforts combined to treat genetically normal but aged mice.
I fully agree on junk.

(Aubrey) My approach to cancer is (as people here probably know) based on the view that no existing or imminent approach will delay cancer deaths by more than 10-20 years.

Do you have any compelling argument, why high-dose chemotherapy followed by complete replacement of all rapidly dividing cells from ex vivo sources could be insufficient? (This would not require any technology that WILT does not. Thus we may even decide between the two at a much later stage.) I believe considerable effort should be put into avoiding the complications and suffering that might result from WILT.

(Aubrey) Immunosenescence...

Hmm I have to catch up on that one.

(Aubrey) The reason I support the Methuselah Mouse Prize as well as the IBG is precisely because I recognise that I may be wrong on the science. In an ideal world there would be several IBG's competing for the MMP -- rather like the X Prize.

[thumb] What a vision...

It has troubled me for a while that one IBG would sacrifice the power of competition. It would be more like NASA than like X-prize...

However, history knows successful examples of the similar Apollo, and Manhattan projects. When the sponsors are determined and rich enough, a centralized agency may be a way to go. There is barely anybody as determined as we are, but rich... erm, well...

Jay, the winner-takes-all threshold it wasn't my idea, (I think David's) but if I had anything to say, I'd vote for it.

#26 Da55id

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Posted 25 January 2005 - 03:12 AM

It has troubled me for a while that one IBG would sacrifice the power of competition. It would be more like NASA than like X-prize...

However, history knows successful examples of the similar Apollo, and Manhattan projects. When the sponsors are determined and rich enough, a centralized agency may be a way to go. There is barely anybody as determined as we are, but rich... erm, well...

Jay, the winner-takes-all threshold it wasn't my idea, (I think David's) but if I had anything to say, I'd vote for it.


The reason Apollo and Manhattan succeeded is that they were both competitions - WAR - one very hot and one very cold.

dg

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Posted 25 January 2005 - 08:51 AM

My reason for not mentioning other nuclear mutations is that I think they don't matter in anytrhing like a normal lifetime; our DNA repair and maintenance machinery has evolved to be good enough to stop us from dying of cancer before middle age, and the rest of our genes, in which dysfunction has to occur not just in one cell but in a fair proportion of the cells in a tissue in order to be harmful, get a free ride.  Jan Vijg has been trying to prove this logic wrong for a decade or more and has so far only provided a lot of evidence that it's correct.

- Intracellular junk, extracellular crosslinks and most types of toxic cells (e.g. excessive visceral fat) are caused by normal metabolic processes, not by mutations.


Good to hear from you Aubrey, always fun and interesting to debate SENS issues with their architect .

From the above I take it that you view nuclear mutations as only responsible for cancer, and since, as you say, cancer generally begins to manifest pathologically in middle age, then the danger is limited to cancer in the middle aged. According to you, nuclear mutations are unrelated to aging and since, from a SENS perspective you have a solution for cancer, that's the end of nuclear mutations. But I think not. I am convinced you have grossly underestimated the effect of nuclear mutations on aging.

If we consider cancer, the prospect of decreasing morbidity by optimizing nuclear DNA maintenance would be a tremendous boon in itself since if cancer is caused by mutations then an optimal DNA repair system would provide a life-long deterrent. But this is not a discussion on a prospective cancer therapy but on the value of research into nuclear DNA repair as an anti-senescence therapy.

So let's look at your assertion that nuclear DNA mutations are not related to aging as this is at the heart of your proposed SENS and, in my view, its Achilles heel.

A review of the relevant literature for research that links aging to DNA damage shows considerable evidence from two groups of studies:
a) premature aging syndromes in humans
b) induced premature aging in model organisms such as mice
A third group of studies that are relevant are those of nonagenarians and centenarians and their incidence of cancer which is comparatively lower than that of the general population. From these studies one can safely draw the conclusion that there is some correlation between aging and DNA damage.

What remains to be discovered are what the mechanisms by which the rate of DNA damage influence aging.

We have good evidence that loss or gain of function mutations will induce tumorigenesis via tumor suppressor genes (TSGs) or oncogenes (OGs) respectively. This, as you say, is a manifestation of middle age. One may observe that the number and location of TSGs or OGs in comparison to the rest of the nuclear genome is rather small, suggesting that it is a statistical possibility that these "high value targets" will eventually be hit in the ongoing process of DNA damage which goes unrepaired. One may ask what is happening to the rest of the genome that is being constantly assaulted by DNA lesions, of which some are permanently left unrepaired?

You may recall a study on human 40+ brain aging in Nature last year (1). What was interesting about this study was that they monitored the transcriptional status of hundreds of genes in the human brain, and observed that after a particular age certain genes began to be downregulated. Examination of the relevant DNA sequences associated with those genes showed signs of DNA damage. The authors suggested that DNA damage contributed to reduced gene expression in the human brain after the age of 40. It would not be surprising if this DNA damage/gene downregulation effect was also present in tissues other than the brain.

One may consider a hypothetical situation where the rate of DNA repair completely compensated for all DNA lesions so that no mutations could occur. Would that would have any impact on aging rate? I dare say that it most certainly would.

Such a line of investigation would be a worthwhile IBG type project.


(1) Gene regulation and DNA damage in the ageing human brain.
Nature. 2004 Jun 24;429(6994):883-91
File is attached for those interested.

Attached Files


Edited by prometheus, 25 January 2005 - 09:18 AM.


#28 jaydfox

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Posted 25 January 2005 - 04:48 PM

My approach to cancer is (as people here probably know) based on the view that no existing or imminent approach will delay cancer deaths by more than 10-20 years.

Do you have any compelling argument, why high-dose chemotherapy followed by complete replacement of all rapidly dividing cells from ex vivo sources could be insufficient? (This would not require any technology that WILT does not. Thus we may even decide between the two at a much later stage.) I believe considerable effort should be put into avoiding the complications and suffering that might result from WILT.

Well, if I may.

As we all hopefully know, the mortality rate doubles every 8 years or so. For most age-related diseases, the mortality rate for a particular disease typically doubles every 6 to 10 years, with faster doubling periods indicating diseases which become more and more prevalent in old age. Cancer would be one of those.

Now, dying from cancer need not take hundreds of tumors: typically, one malignant tumor will suffice. If cancer mortality rates double every 7 years or so (just an educated guess), then it stands to reason that, if your odds of developing a malignant tumor are 1 in 10 at age 80, then the odds are about 1 in 5 at age 87 (just making up the numbers).

Well, at some point, the odds are so high that you are probably going to develop multiple tumors per year. Luckily, there seems to be a plateau in the rate of cancer formation. However, whether this plateau would apply to everyone, or only to those lucky enough not to have died by the time they reach 100, I can't say. My gut feeling is that, if you should have died from cancer in your 50's, but cancer treatments saved you, then you're probably the type of person whose cancer formation rate will not plateau as early as the typical centenarian's. In other words, you might need to be in permanent chemo, fighting multiple malignant tumors, for the rest of your life.

You see, chemo doesn't cure cancer and simultaneously innoculate you against further cancer. It just cures the one cancer. Stop treatment, and the next round of cancer is free to attack your now weakened body.

So I agree with Dr. de Grey that treatment will be a losing battle. By society's scale, 10-20 years of extra life is a boon. But for us immortalists, who know how much more life is possible and desirable, those 10-20 years are only going to be a single step on the route to escape velocity.

A long-term cure for cancer would thus involve securing nuclear DNA. Using de Grey's WILT strategy, we can expect only an order of magnitude or better results than continuous chemo. Sure, WILT will prevent a malignant tumor from growing big enough to kill you. But what happens when your genome is so damaged that ten or fifteen or fifty malignant tumors are forming every year? We may not need to secure the nuclear DNA right away, but it will have to be done, sooner or later. That, or WGRT (Whole-body Genome Replacement Therapy). It's not a very catchy acronym anyway.

And thankfully, improving DNA-repair is not any more expensive to research than the other areas of SENS, and probably quite a bit cheaper. Sure, securing DNA against all mutations is probably next to impossible. But nature is already capable of decreasing DNA damage rates by a hefty percentage in times of stress, so we can start there. It makes sense to look to bacteria to find enzymes that can break down tough intracellular junk. Doesn't it also make sense to look to other species for genetic material (encoding proteins, enzymes, mRNA, whatever...) that can increase DNA-repair rates, or otherwise better protect nuclear DNA? Some would take us in the direction of studying extremely long-lived species, and that study certainly has it place. But there's still so much to learn about basic DNA-repair strategies (which are not inherently species- or phyla-specific) from short-lived, cheap species.

Anyway, just nudging the debate along.

#29 eternaltraveler

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Posted 25 January 2005 - 06:11 PM

Do you have any compelling argument, why high-dose chemotherapy followed by complete replacement of all rapidly dividing cells from ex vivo sources could be insufficient? (This would not require any technology that WILT does not. Thus we may even decide between the two at a much later stage.) I believe considerable effort should be put into avoiding the complications and suffering that might result from WILT.


I have a very compelling and very simple argument.

There are plenty of cancers that are not due to rapidly dividing cells. My grandfather currently has cancer that his physicans plan to do absolutely nothing about. Why? Well he's 85 right now and they estimate it will be more than 20 years before this cancer becomes a danger. The treatment is far more likely to be the cause of his death rather than the cancer it self.

Another simple argument is that many kinds of chemotherapy are potent carcinogens (even the more gentle modern kinds certainly aren't good for you). People often develop new cancers as a result of their chemo.

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#30 eternaltraveler

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Posted 25 January 2005 - 06:14 PM

a real cure for cancer would have to be something like WILT. This however is one of Aubrey's 7 that I personally believe will be achieved later rather than sooner (perhaps last out of the 7)




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