From: Joao Pedro de Magalhaes (joao.magalhaes@fundp.ac.be)
Date: Tue May 02 2000 - 05:23:05 MDT
Hi!
First of all, I'm very busy for the next two weeks and therefore this is
sort of a quick reply.
CurtAdams wrote:
>> And it's been known since the 60's that
>> cells from old animals put in a tissue culture divide less than that of
>younger
>> ones from the same species,
>
>Actually there are studies on both sides of that; just recently I saw a
>mention
>of some study that "conclusively proved" old human cells do not divide less
>than cells from young adults (so obviously the issue is still open).
I mantain my previous statement that cells taken from human donors
post-partum do no show a correlation between population doublings in vitro
and age of donor. For refs check Cristofalo and de Francheschi (I hope to
have the bibliography of my website ready in the next couple of weeks, check
it out and you will find all relevant articles there). I can also tell you
that studies done in our lab -- though not published for only a few samples
were taken -- reached the same conclusion.
>Fetal
>cells *do* outlast adult cells; but that may be a different process.
I agree.
>But telomere lengths differ between organisms. Mice
>have very long telomeres; we don't.
I think it's nice to point that humans have the shortest telomeres amongst
all studied primates in a given study (I'll give the ref later if you want
it). Another interesting point is that average telomere lenght might not be
involved in aging but, on the other hand, specific telomere lenght in only
one or a few chromossomes might affect aging (thus biasing most of our
current reasoning).
John K Clark wrote.
> >There is no correlation between in vitro doubling potential from cells taken
> >post-partum and life span.
>
> you get more in vitro cell divisions from long
>lived species than from short lived ones.
ANother interesting idea: long-lived species are bigger in size and mass,
which means their cells need to endure more divisions during development and
even adulthood (actually I believe somewhere I have an article showing a
relation between mass of a spoecies and replicative potential of its cells
in vitro).
Robert J. Bradbury wrote:
>> 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.
>
>That would be a useful bit of information. What would be *very* interesting
>would be to compare clones produced from normally dividing cells, such
>as intestinal cells as I believe was the case with Dolly, cells with
>replicative potential (liver), and non-dividing cells (neurons, muscle, ???).
>The question is whether the non-dividing cell can be dedifferentated
>back to a dividing state.
I may be wrong but I believe scientists have accomplished in creating
dividing stem cells from post-mitotic tissues such as neurons (must search
reference).
>If you could do that, then you could use
>cells from young, middle-aged & old animals and really get a handle
>on the degree to which mutation accumulation damages genome integrity.
That would be a very useful experiment.
>Joao, you may know the answer to this. Wasn't there a report
>(perhaps from Univ. of Hawaii?) that telomerase knockout mice *do*
>show signs of inability to develop and/or accelerated aging after
>3-4 generations?
I believe you answered your own question in a posterior post.
>If that is true, it might suggest that normal
>telomere lengths in adults would be sufficient to develop 2nd
>generation and perhaps even 3rd generation organs from stem cells
>remaining in the adult body, *without* the necessity of lengthening
>the telomeres through cloning or other processes. Presumably
>more terminally differentiated cells (that have gone through
>more cell divisions) would be a poorer source material due
>to shorter telomeres, *if* you could regress them to a
>stem cell state. Now, given the shorter telomeres in humans
>it would be unclear whether the stem cells in adult humans
>could be used to grow replacement organs.
>
>What we need is the # of cell generations required to produce
>a 3-5 kg organ from a single cell, the normal adult human telomere
>length and how much each cell division subtracts from the telomeres.
I don't have time but I think that can be calculated easily for in vitro
cells. As for in vivo, you would find a harder time defining the amount of
telomeres lost per generation for it depends on tissues but eventually would
get and aproximate value.
Best regards and I apologize if I wrote any imperfection.
---
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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