16 replies to this topic

[John Schloendorn]

It seems to me that there is a strong consensus that robust mouse rejuvenation, or some other psychological break-through is going to release massive amounts of funding for the development of human rejuvenation therapies. I would like to have a closer look at this idea.

Deathists seem to me to emphasize the undesirability of rejuvenation over its infeasibility lately. Do you agree with this observation? Quite amazing things have already been demonstrated in worms and the public is almost certainly unaware of why these results mechanistically have relatively little to do with future mammalian rejuvenation. Thus, further pushing for demonstrations of the feasibility of life-extension may be somewhat on the wrong track.

Should more attention (i.e. millions of dollars, if we can raise them) be invested in tilting the public opinion, rather than in actual attempts of mouse life extension?

Should more plans be made for the case that large scale public support can never be obtained for the idea of human life extension, even if it were demonstrably possible?

[Lazarus Long]

Deathists seem to me to emphasize the undesirability of rejuvenation over its infeasibility lately. Do you agree with this observation?

Absolutely John I have noticed the exact same thing and it implies they actually agree that time, tech, and basic science are on our side and they are seeking to preempt our attempts before they can create hope.

[Lazarus Long]

In my view, lots more work needs to be done on basic science before we can start cheering.

Indubitably Prometheus, I was just commenting on the fact that it appears that the opposition seems to be crediting the possibility as real too. This is a serious strategic vulnerability IMHO.

In fact I suspect we have far more realistic perspectives than they do but it is interesting to note how the push is to preempt as if they have already granted the potential of the tech as inevitable.

Edited by Lazarus Long, 16 February 2005 - 12:37 PM.

[eternaltraveler]

Plus we don't need to convince the majority of people for massive funding to be available. Even 10% of the people in this country would probably be enough. That's 30 million people. If on average they donated just 20 bucks a piece thats still 600 million dollars. If there's just a few particularly weathly people in that 30 million then the total would likely be significantly higher.

This says nothing of government or corporate funding.

The funding will be available after robust mouse rejuvenation exists.

[ag24]

What has been omitted in this thread so far is the role of stated scientific opinion. The only reason I'm so sure that RMR will trigger the War On Aging is that I'm sure that my senior colleagues will mostly respond in the media to the achievement of RMR by saying that, yes indeed, we may be in range of RHR. Public opinion will follow the stated scientific consensus in this just as it always does. John is quite right that the public don't know the details of why sextupling worm lifespan means little for humans, but (my favourite phrase) they don't need to know: they just see what my colleagues say and don't say on the TV about what it means, and draw the correct conclusion.

[jaydfox]

Pardon my ignorance, but I can only read so many papers a day. It may be a while before I'm caught up.

I remember discussions about WILT where de Grey stated that WILT would be ineffective in mice, due to their small size relative to the growth limit of tumors imposed by WILT (and due to their longer telomeres, but we can engineer those to the length in humans for comparison, I assume).

I assume that even shorter telomeres could be used (shorter than in humans if necessary), with the consequent increase in frequency of stem cell replenishments (which will have to be more often to due higher metabolism and cell turnover anyway). Instead of every ten years, we're looking at every year, perhaps even every few months. In a lab, that's doable, right?

It's possible, I suppose, with frequent enough reseedings. However, I get the impression that WILT will not be nearly as easy or effective in mice as in humans. How does this bode for engineering RMR? Will the other 6 aspects of SENS be sufficient to make up for this deficiency in the 7th aspect?

I'm not addressing the human efficacy of WILT, just the mouse efficacy. Obviously, if it can be made to work in mice, then that's all the more reason to believe it will be effective in humans. Conversely, even if it's not possible in mice, that's not evidence that it won't work in humans. In this respect, I'm assuming that mice are not the ideal research model for WILT. That's beside the point. What is the point is that funding is predicated on RMR. Which means funding is predicated on the effectiveness of WILT in mice.

[John Schloendorn]

The only reason I'm so sure that RMR will trigger the War On Aging is that I'm sure that my senior colleagues will mostly respond in the media to the achievement of RMR by saying that, yes indeed, we may be in range of RHR.

Good point. That's how things went in that touching Dragon Tyrant story I just finished. Sniff.

[John Schloendorn]

But I'll have another go. What will happen to the public could mimick what I have experienced in a number of personal conversations. It goes roughly like this:

s.o. "Curing aging, well sure that'd be nice, but it's impossible!"
J.S. "So? Well here's what they did to a worm, here's the results of a recent straw poll of the world leading biogerontologists at IABG10, and here's the concept of escape velocity."
s.o. "Argh - WHAT? Are you insane? There would be overpopulation, and anyways aging is just what makes us human!"
J.S. [Reiterates http://www.gen.cam.a...ns/concerns.htm]
s.o. "You're a dreamer! Curing aging is impossible!"
J.S. "Remember were we started?"
s.o. "Ok, I openly admit, I'm a bit out of arguments right now, but if I had studied these arguments for as long as you did, I'm sure I could beat you easily!"
J.S. "Darn..."

Where would they run, where would they hide? To admit that one was wrong on such an outrageously important, and yet fundamentally easy to see-through matter as the desirability of healthy life extension is to admit that one was just extremely stupid for one's entire life. What would one say to the dependents of those 100,000 people a day who died because of one's stupidity and consequent inaction? The need for self-esteem won't have it. I've seen such staggering amounts of coping, suppression and irrationality, whenever "life-extension" was only alluded to. Hence are my doubts that even a rejuvenated mouse and a bunch of enthusiastic senior gerontologists can change that over night. Maybe it takes as much as a personal encounter with a RHR recipient to really get through to people. Remember the catholic pope who finally apologized to Galilei, admitting that the earth is actually a sphere? I think it was in 1987...

Still, in sum, I would agree with Elrond that RMR might give us at least something, possibliy enough, and with Aubrey that this is the best shot we've presently got.

Edited by John Schloendorn, 21 February 2005 - 11:20 AM.

[John Schloendorn]

I'm assuming that mice are not the ideal research model for WILT. That's beside the point. What is the point is that funding is predicated on RMR. Which means funding is predicated on the effectiveness of WILT in mice.

WILT is problematic, not only for this reason, but this is another good reason. The major reason to believe that WILT would be less effective in mice (telomere lenght/body size ratio) may be *fairly* straightforward to address by using late-generation telomerase knockouts and/or short-telomered mouse species (peromyscus) to do the further WILT engineering with.

If one attempts to go SENS without WILT, then one may consider using germline engineering to confer increased cancer resistance to these mice, in order to keep them alive long enough to demonstrate the full extend of the anti aging interventions. But one could not win a MMP with it, nor be anywhere near as convincing to the public as when the entire intervention were late-life.

It may also not be a hopeless case of optimism to wager that cellular replacement in all dividing tissues will do enough to reduce cancer to allow for RMR without WILT, but using a much more primitive cell ablation scheme. At least it should be worth a shot.

In the end, I think we should just wait for (and work to promote) the future development of cellular replacement technology, before we make a definite choice on WILT.

[John Schloendorn]

Prom, if one replaces WILT (WILT in the literal sense, i.e. ONLY deletion of telomere lengthening) by another, much easier cell ablation scheme, but sticks with the cell replenishment (as I suggested) then nDNA mutations would still be obviated. (Provided that the replacement cells are chosen appropriately, i.e. do not contain mutations)

[jaydfox]

Prom, if one replaces WILT (WILT in the literal sense, i.e. ONLY deletion of telomere lengthening) by another, much easier cell ablation scheme, but sticks with the cell replenishment (as I suggested) then nDNA mutations would still be obviated. (Provided that the replacement cells are chosen appropriately, i.e. do not contain mutations)

But SENS as presently constituted has no such backup plan, and its architect is not only not considering such options, but actively resisting them.

It may also not be a hopeless case of optimism to wager that cellular replacement in all dividing tissues will do enough to reduce cancer to allow for RMR without WILT, but using a much more primitive cell ablation scheme. At least it should be worth a shot.

That's what we've been trying to say!

[John Schloendorn]

I can see that Aubrey is open to the idea that other cell ablation schemes than WILT are useful and promising. For example:

Sounds good to me. All I would really say is that in this context WILT is a sort of insurance policy to make sure that we aren't relying on perfect 100% elimination of all the cells with the suiucide genes.

And, if the SENS2 program is any indication for Aubrey's priority distribution, then I can see that Aubrey strongly pushes for cellular replenishment schemes: Three out of ten sessions focus exclusively on cell replenishment methods and others (cancer, immune, ect) can be expected to make indirect reference to it. Furthermore, the cancer people can be expected to be all about cellular ablation without WILT (Telling from their present work they're supposed to present). Now what on earth makes you call this behavior "actively resisting" cell replacement options?

[jaydfox]

Well, he's resisting it here, at least with respect to increasing DNA integrity, and he has done so consistently for some time. However, I'm glad to hear that he's at least pursuing the alternatives in his scientific arena.

Furthermore, I've been trying to get across that we don't need WILT as a last resort, because its risks outweight its benefits. Sure, keep it on the back burner, but don't keep it on the front burner with DNA repair on the back burner. DNA repair belongs on the front burner.

Pushing WILT as the primary weapon against DNA damage, if not his main scientific weapon in his arsenal, seems like a publicity stunt. Which Prometheus has been arguing against for some time.