Re : Telomeres and stuff

From: Joao Pedro de Magalhaes (
Date: Mon May 01 2000 - 03:54:38 MDT


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

>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
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