Reason = rambling crackpot

Today's fun media mention.

http://www.boston.co...e_for_the_ages/

http://www.fightagin...ives/000382.php

The Aubrey de Grey - Snuffy Smith resemblance isn't something I'd considered before either...

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

keep rambling on.. [lol]

Hmm, their website is crawling at the moment, and I can't get past the ads at the top before it craps out.

Still, it's been an honor to work with and be inspired by such an invading crackpot as yourself.

Cool. More publicity.

It is amazing how many different stripes of people are so arrogant (or ignorant). Professors, journalists, politicians, etc... I am amazed at how quickly they resort to ad hominem attacks. You know what, it makes me feel that we are winning the PR battle. The other side is either too dumb to come up with intelligent challenges or they are so scared that they immediately resort to demonization.

Damn these fine articles - making me spray porridge all over my screen as well as getting it stuck in my nasal passages - could not contain the laughter.

I am delighted for you Reason - enjoy the traffic!

It is also gratifying to see Justin cop some flak over his irresponsible editorial.

Back to the TR Forum, however, Estep critiques SENS:

... unlike Sherwin Nuland or other casual critics of the SENS plan -- and unacknowledged by Dr. de Grey -- mainstream scientists have produced substantial evidence not addressed by de Grey and his plan. More importantly, certain of these data are related in a way that gives the immortalist or transhumanist particular discomfort since they suggest that the SENS plan does not address the primary -- and maybe the most difficult to control -- general aspect of aging: entropy.

In plain English, the loss of order and information essential for biological function.


Also known as mutation - in the nuclear genome as well as mitochondrial. This is a valid point that has yet to be ackowledged.

Aubrey's response to this point:

He alludes to the existence of "substantial evidence not
addressed" by me and SENS, but the only references he
gives are to the changes of gene expression with age,
which of course occur but do not tell us anything about
what can be done to reverse them.


It is not Estep's concern to find a solution to a problem that Aubrey chooses to ignore, merely to point out what is a glaring omission of SENS. Aubrey is obviously sidestepping the issue and using Estep's references as a point of contention, a tactic that he used in a recent exchange in these forums.

The DNA damage problem will continue to be the major source of criticism of SENS in its present incarnation. It's time that SENS addressed it.

Edited by prometheus, 03 February 2005 - 10:55 PM.

In all fairness to Aubrey, I should point out that he believes that SENS already addresses the DNA damage problem. Mitochondrial DNA damage is dealt with his proposal of moving the mitochondrial genome into the relatively less mutagenic environment of the nucleus and nuclear DNA damage is dealt with via the two pronged strategy of WILT - destroy all telomerase in the body and periodically replace telomerase positive cell dependent tissues using telomerase negative stem cells.

Both strategies rely on science and technology as yet undiscovered, and in my view are convoluted approaches to solving the DNA damage problem which can be dealt with far more elegantly. Present gene therapy technology enable persistent and non-genome integrating expression of transgenes. Furthermore, such expression can be controlled using inducible promoter systems able to switch transgene activity on by enabling the coupling of certain conditions to transgene expression.

Increasing the performance of DNA maintenance systems seems a far more direct solution to the problem - a strategy that can be therapeutically validated using contemporary technology, and be made available within this decade.

Back to the TR Forum, however, Estep critiques SENS:

... unlike Sherwin Nuland or other casual critics of the SENS plan -- and unacknowledged by Dr. de Grey -- mainstream scientists have produced substantial evidence not addressed by de Grey and his plan. More importantly, certain of these data are related in a way that gives the immortalist or transhumanist particular discomfort since they suggest that the SENS plan does not address the primary -- and maybe the most difficult to control -- general aspect of aging: entropy.

In plain English, the loss of order and information essential for biological function.


Also known as mutation -  in the nuclear genome as well as mitochondrial. This is a valid point that has yet to be ackowledged.

The DNA damage problem will continue to be the major source of criticism of SENS in its present incarnation. It's time that SENS addressed it.

These are legitimate criticisms, unlike what we've been exposed to recently in the media. Unfortunately I'm no expert in this area, but entropy is a fundamental reality in this universe and we'll have to face that reality as the attempt is made to extend human lives beyond their evolutionary limits.

Aubrey's timeline for life extension may be somewhat optimistic, but I think it's more realistic compared to other biogerentologists who have very conservative predictions for human lifespans in the future.

I am impressed!


I know about editors, navigators, advisors, and now directors, aside from full members and basic members, of this here ImmInst org.

Glad to know about directors.

I am chastened, in the face of such learning in the matter of life extension.

And I am still at the stage of distinguishing the mundane from the arcane, the drab world from the garb world, the dismal life from the ideal life, and now most recently, the creational universe from the recreational universe.

I think your concern about life extension is into the mundane, drab, dismal, and creational dimensions of human existence and his universe. Congratulations!

You don't belong to the arcane, garb, ideal, and recreational world of Buddhists and some philosophers of today who are into dense writing in the exposition of their thoughts.

What do you say, shall we consign longevity to engineers and technicians, instead of biologists, medical doctors, chemists? but these are also in fact engineers and technicians.

Thanks for your contributions to my education.

So, Reason you are the founder of longevity and fightaging? Amazing! I can't say the same thing about myself, how you can put so much time and labor into this web activity and publicity, and yet have time for the mundane, drab, dismal and creational life of your income-generating work, home, and family.

Some people are indeed more versatile, resourceful, and productive than others.

Susma

Aubrey's timeline for life extension may be somewhat optimistic, but I think it's more realistic compared to other biogerentologists who have very conservative predictions for human lifespans in the future.

Closer to realism in terms of what is possible, I should add - but what actually happens in terms of funding and actual research done in the years ahead is very much up in the air. Hence the need for all this activism, spreading the word, etc.

So, Reason you are the founder of longevity and fightaging? Amazing! I can't say the same thing about myself, how you can put so much time and labor into this web activity and publicity, and yet have time for the mundane, drab, dismal and creational life of your income-generating work, home, and family.

Some people are indeed more versatile, resourceful, and productive than others.

This assumes I have a life outside doing this stuff

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

Actually prometheus,

Aubrey's response to the entropy is required for life argument is

"Estep's error in his argument about entropy is to overlook
the fact that cells introduced into the body in a cell therapy
(of any kind) will in general have less entropy than the ones
they replace did. He is quite right that they consume
information while they are settling in, but thereafter they
provide it. This can maintain a high degree of order
indefinitely, even in the face of increasing entropy of all
cells while in situ. "

which I think says it pretty well..

Actually prometheus, Aubrey's response to the entropy is required for life argument is

"Estep's error in his argument about entropy is to overlook
the fact that cells introduced into the body in a cell therapy
(of any kind) will in general have less entropy than the ones
they replace did. He is quite right that they consume
information while they are settling in, but thereafter they
provide it. This can maintain a high degree of order
indefinitely, even in the face of increasing entropy of all
cells while in situ. "

which I think says it pretty well..

In fact what Aubrey's response says is that new stem cells that are grafted/transplanted into the host have less entropy (DNA damage/mutation) than the host cells. A statement that would be correct providing the source of stem cells has less DNA damage. This, as I explained in the previous post, is one arm of WILT (the other being to eliminate telomerase expression).

The proviso, as Estep mentioned, is whether we can develop the technology to direct stem cells to repopulate and regenerate specific tissues. In due course I am confident this will be achieved and that such approaches will form the core of the next evolution of medicine which is directed regeneration.

Is this the best solution for the problem? And is such a solution in keeping with Aubrey's self-proclaimed "engineering approach" of finding the shortest distance between two points? Not necessarily when a far more rapid and implementable solution of dealing with the root of the problem - DNA damage - is available.

Furthermore, completely regenerative therapies may not be suitable for all sorts of tissue. Consider the brain as a special example: when dealing with Parkinson's disease, replacing damaged dopamine producing cells in the substantia nigra using stem cells is a fine approach. Rapidly replacing neurons associated with cognitive brain functions and long term memory, however, could have serious side effects involving loss of memory and existing personality traits. In such critical neurons it would be preferable to replace supporting glial cells using stem cells and rather then replace the neurons themselves aim to slow down their aging process by increasing genomic integrity. Eventually even these cells would have to be replaced, but by slowing down the rate of replacement would have less of an impact on personality.

What Aubrey's response does not address, and wherein a superior solution lies, is the foundation for cellular entropy - DNA damage. Increasing the performance of DNA integrity systems in cells as well as removing the telomerase limited cell division ceiling would provide for the fastest way to implement a reduction in senescence and cancer.

It kind of reminds me of the debate between the hydrogen fuel cell camp and the hybrid-engine (with zero-net-CO2 emission fuels) camp.

The former is much more ambitious, and in the long run, probably a better solution, assuming that certain technical barriers are overcome. Yet they ignore the massive economic burden that shifting to such an economy would bring, when hybrid cars can provide a good bridge to get through the next decade, and an emphasis on zero-net-CO2 emission fuels would eliminate much of the need to improve on that design for some time to come.

Who's right and who's wrong? I don't know. Like many of these debates, there are major technical issues to consider, but also major economic issues. But it's plain silly for the hydrogen camp to ignore the merits of hybrid engines with zero-net-CO2 emission fuels. If nothing else, the orders of magnitude in cost difference almost demand that we proceed with hybrids first, just to buy us time to improve the tech for hydrogen cars and infrastructure.

Who knows, maybe WILT will be the way to go. I'm certainly less qualified than either de Grey or Prometheus to make a judgment on that issue. But I can at least see that the DNA maintenance approach is far less expensive to research, relies on available or nearly available technology, and can use any of a variety of cheaper, shorter-lived organisms to do the initial research, with more focused validation research in mice.

My thinking is that the 7 targets of SENS are things that de Grey sees as mandatory to fix. Fix 6 of the 7, and you're still gonna die of "aging" eventually. Maybe you can sustain someone with the 7 points of SENS without improving DNA repair. But A) the time when our technical ability to implement all 7 aspects of SENS well enough to ensure that DNA repair is obviated is probably a long ways away, probably a decade or two after SENS even becomes available, which is itself several decades away, and B) better DNA repair can only make SENS more effective, and require a less-perfect implementation of SENS to get the job done.

So even if it's not "mandatory", it still seems like a really good idea. The upshot is, it can be researched, validated, and put to human safety trials in less than a decade, perhaps up to two decades if we're terribly conservative, and be available as a bridge for those who might not otherwise last long enough for SENS, which could be three to six decades away.

Reason = rambling crackpot

Maybe we should collect such names, and put them as trophies under the imminst name of the members that attracted them. (read my envy? )

Actually, the hydrogen fuel cell analogy was kind of off the cuff, but in my walk to the breakroom to get some cold/pain medicine (getting over a particularly bad bout with the flu), I thought of a better way to use the analogy.

Disclaimer: First of all, don't draw too much from this analogy, as analogies can only be so useful. Maybe the hydrogen fuel cell direction is the wrong direction, and SENS is the right direction, or vice versa. I'm just looking at the dynamics of the setting up the plans to move forward.

Think of SENS as the hydrogren fuel cell camp, putting in place a vision that removes our dependence on (foreign) oil. A bold and ambitious plan, but one that requires fancy new tech and a huge new infrastructure (much like the many, many, many new doctors, nurses, hospitals, etc., that would be required to administer the longevity treatments, assuming that everybody wants them).

Okay, that's all and well. On the other side is the fuel economy camp: hybrid technology, better aerodynamics, better tires (better grip to frictive energy loss ratio), lighter materials, etc.

As I see it, the hydrogen camp wants little to do with the fuel economy camp. With hydrogen fuel, we don't have the limited supply of fossil fuels, nor the political risks associated therewith, so what's the issue? Hydrogen's virtually unlimited, and with domestic power supplies (wind, solar, nuclear, etc.), the political risks of foreign dependence are mitigated, as is the issue of non-renewables (well, except for nuclear, but fusion's on the way...)

Well, I guess if you've got all the hydrogen in the world, it's not a big issue. But, wouldn't the size/cost of the huge new infrastructure required to put hydrogen into play be reduced considerably if less hydrogen were needed in the first place? And wouldn't it be convenient to drivers if they could drive a lot farther on a tank of H if they get better fuel economy? And given the considerably smaller costs of improving fuel economy, wouldn't it make sense for the hydrogen camp to embrace the ideas of the fuel economy camp? Regardless of whether or not the fuel economy camp thinks that hydrogen fuel is necessary?

So what if Prometheus doesn't like all aspects of SENS. Hey, would it even matter if he thought the idea was plain wrong on all counts? I don't think so. What matters is that he and other scientists are raising a very valid concern, and it wouldn't hurt to add it to SENS. It makes SENS more robust. And luckily, it would A) be one of the cheaper aspects of SENS to research, and B) it's research that will happen in a less ambitious form anyway (e.g. CR mimetics, a more primitive version of what Prometheus and others propose), so the cost would be something borne by the economy, rather than the IBG, to a certain extent.

There's no reason a hydrogen-fuel cell powered car couldn't use regenerative braking to a battery/capacitor, be aerodynamically sleek, have efficient tires, and be very light and strong. Likewise, I don't see why SENS couldn't incorporate some better nuclear DNA management. Sure, it would make the plan even more ambitious, which might make it look like curing aging is harder, and I know de Grey wants to make it clear that curing aging is not incredibly difficult, even if it is fairly difficult.

two years ago there was zero groundswell of articles dealing with reversing aging - now there is. The M Prize and SENs proposals are bringing the conversation out of the closet...and as you would expect, many folks don't like the way the lapels look. Well, if they don't like the first one, then lets everybody tailor the experiment that suits them ;-)

(from Ghandi)
First they ignore you: This period is now at the middle
Then they laugh at you: This is just starting...
Then they fight you: We won't like this part
Then we win: