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#31 jwb1234567890

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Posted 04 March 2005 - 05:52 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.

Unfortunately it is not within my powers to give you a formal invitation as I am unconnected with it. For sure if you do come over to blighty you should be prepared for any weather... today it was snowy then sleety then rainy and finally the sun came out.

Well your theories are compelling and you have easily got enough there for it be classed as novel and innovative so I hope you do end up presenting your paper in Cambridge. It is true that it is a fair outlay of cash and more time will make your theories more mature but on the other hand no body here is getting any younger:) Anyhow I hope I get to go to the conference and see your presentation there.

And at the end of the day you get to have world class gerontologists looking at your work, if it survives that review then Aubreys going to be hard pressed to keep it out of SENS, that would be senseless.


#32 jaydfox

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Posted 04 March 2005 - 06:18 PM

...Aubreys going to be hard pressed to keep it out of SENS, that would be senseless.

Again with the SENS jokes... [huh] Someone should knock some SENS into you people! [:o]

#33 jaydfox

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Posted 04 March 2005 - 10:07 PM

>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.

I didn't see anyone else address this, so forgive me if someone did.

As far as I can tell, Aubrey inferred the ten year figure from two studies (don't have the references, but Aubrey surely can provide them if you'd like):
1) age of onset of dyskeratosis congenita
2) no substantially earlier phenotype for gut or blood disorders in telomerase-knockout mice in late generations.

In other words, gut and blood disorders from telomeric catastrophe (is there a more precise technical term for this?) should occur not much earlier than skin disorders, and skin disorders are predicted to come not much earlier than 10 years at worst, so we're looking at a decadal reseeding time, give or take a small margin.

The main problem with this is that (2) was done in mice, not humans. The second problem is that this seems to be in direct conflict with studies pointed out by Prometheus on gut stem cell division rates.

Which is why I bothered to go to the effort of summarizing the gut issue here. Basically, if Prometheus is right, WILT won't work. If de Grey is right, then WILT might not be as necessary as he claims. (Note I say "as necessary", as opposed to "necessary". It might still be necessary, so we shouldn't abandon WILT by any means.)

Quote from the SENS website, where I pulled (1):

The telomere reserve of neonatal stem cells suffices for about a decade, judging from the age of onset of dyskeratosis congenita, a disease associated with inadequate telomere maintenance. So, in theory, a decadal repopulation of all our stem cell populations with new ones whose telomeres had been restored ex vivo, but which had no telomerase or ALT genes of their own, should maintain the relevant tissues indefinitely while preventing any cancer from reaching a life-threatening stage.

#34 ag24

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Posted 04 March 2005 - 10:34 PM

Good question Jay. See Abkowitz et al 2000, Blood 96:3399 for a calculation of blood stem cell division rates in humans (cited in the WILT paper, incidentally). Shortly after the WILT paper was published, Abkowitz's group came up with a considerably slower rate: see Exp Hematol 32:1040. I should probably add this to the relevant page on my site. Dyskeratosis congenita is named for its skin phenotype but sufferers get blood problems at the same time usually. The age of onset of DC is actually a rather over-pessimistic estimate as cell division is far faster before birth.

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