From: Joao Pedro de Magalhaes (joao.magalhaes@fundp.ac.be)
Date: Mon May 01 2000 - 03:54:38 MDT
Hi!
Robert Bradbury wrote:
>
>I wrote:
>> Cloning experiments are useful for they contradict in many ways the theory
>> of DNA accumulating mutations (this particular experiment doesn't do that
>> because the cells were "aged" in vitro after being taken from a fetus but
>> other experiments do just that, despite the data no being conclusive).
>>
>
>I disagree. With the cloning success rates so low, you have no idea
>whether the failures are due to scientific methodology or whether
>you have a situation where only 5% of the cells contain an "intact"
>developmental program.
I believe -- can't find the reference -- some Asian scientists cloning mice
did find a correlation between donor age of the nucleus and the chances of
creating a viable clone. However, for DNA mutations to cause aging they must
accumulate a great number of mutations per cell, of which a few you would
expect to be present in clones visibly affecting their physiology. There
are, of course, other arguments: perhaps the DNA was damaged but was correct
by the superior power of the egg to repair DNA (the repair of the telomeres
in this experiment is a good example of DNA repair); or the fact that in
this particular experiment the control clones (with nucleus from cells not
aged in vitro) did not show a different success in creating viable calfs.
Without being conclusive, I still think clones do harm the DNA mutation
theory.
>The cloning experiments *may* be saying something very interesting
>about the DNA mutation theory. The only way I can see to shed some
>light on this will be when we have good DNA polymorphism chips
>that can allow you to measure the "noise" (mutation) level in the genome.
>Then you take 2000 cells, split them, measure the effective mutation
>level in each "clone" at the same time you try to make an organism
>out of them. If the mutation rate (genome noise level) is lower
>in those clones that produce successful organisms, then you
>have a smoking gun for the DNA mutation accumulation theory.
Well, of course that if someone does that we'll have some answers.
John K Clark wrote:
> "In a related experiment, the team cloned five calf fetuses from adult cells
> kept in culture until senescence. They removed the fetuses at 6 weeks
> of gestation so they could compare their cells with those of normal fetal
> calves. The clones' cells divided an average of 93 times compared to
> only 61 for cells from normal calves. If this increased life-span extends
> to the whole animal, Lanes says, there is "a real possibility" that cloned
> animals might live as much as 50% longer than their normal counterparts
> --up to 180 to 200 years in the case of humans--an idea, he says, that
> "is going to raise an eyebrow or two.""
>
> That's even more direct evidence. I grant you it still doesn't prove the
> entire animal will live longer but it does give considerable weight to
> that idea; and a increase from 61 to 93 divisions is not small and is not
> theoretical, it's a concrete experimental result.
Mice having shorter telomeres at birth do not live less than controls. There
is no correlation between in vitro doubling potential from cells taken
post-partum and life span. Therefore it is unlikely that we will witness a
50% or close increase in the life span in these animals. I personaly am more
interested in seeing the results from Blasco's knock in telomerase mice.
> > Ever since Fossil's book, everyone has thought that "aging" is
> > associated with telomere shortening and quite simply that is crap.
>
>It sounds like you're saying that there is no possibility telomere shortening
>has anything to do with aging, not in any way shape or form. Skepticism is
>always healthy in science but cynicism is not and I don't think the evidence
>can support such an extreme view.
As I believe I've said before, telomeres do appear to be related to aging
but are hardly the final picture.
Best regards.
---
Joao Pedro de Magalhaes
The University of Namur (FUNDP)
Unit of Cellular Biochemistry & Biology
Rue de Bruxelles, 61
B-5000 Namur BELGIUM
Fax: + 32 81 724135
Phone: + 32 81 724133
Reason's Triumph: http://users.compaqnet.be/jpnitya/
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