From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Mon Mar 10 2003 - 13:46:40 MST
On Mon, 10 Mar 2003, Joao Magalhaes wrote:
> Yet I'm not so sure about your other examples of accelerated aging
> diseases. I read last week's Science paper on these disease and I'm
> still not convinced. I have a hunch that understanding the Werner
> protein will be crucial to understand aging, but I think you have to be
> careful if you assume the other diseases you mention to be accelerated
> aging.
I understand -- I would consider them more "partial" diseases of
aging, in that they usually promote certain kinds of cancer.
> It's a similar problem to that of using animal models. You can
> never be sure that similar mechanisms are at work, so I would advise
> caution when extrapolating into human aging.
I know, I've got a recent paper on the ATM gene in Nature that
discusses the fact that the serine that gets phorphorylated to
trigger the entire cascade of DNA repair in response to ionizing
radiation only exists in the mammals and frogs -- not in the
homologues in lower organisms like C. Elegans.
However, because we have all the genes recognized now, if we can't
figure out how the entire DNA repair system works in less than 5
years, then we are going to look really stupid.
I'm reasonably convinced that double strand break repair is a major
cause of aging (it corrupts the code) and that how fast you age
depends a lot on whether the cells tip DSBR towards homologous
recombination (HR) which allows gene conversion, therefore increasing
the likelyhood of cancer or non-homologous end-joining (NHEJ)
which literally corrupts the code. Corrupting the code is very
bad from a programmer's point of view -- from a biologist's point
of view it leads to a number of downstream negative consequences.
I think how fast and in which tissues you age depends to a large
extent on whether DSBR is tipped towards HR or NHEJ. Either path
is likely to involve some of the DNA repair genes that either contribute
to causing DSB or fixing them (you have something like 120+ DNA repair
genes but there are less than probably 2 dozen involved in the
increased cancer/aging syndromes.
I've got a paper half-written about this, if I ever get it finished
I'll send you an advance copy.
> Finally, I have an optimistic (?) article published in this month's
> issue of The Futurist on aging and longevity entitled "Winning the war
> against aging".
I know, I saw it but haven't had a chance to read it yet. (I get The
Futurist but rarely have time to read much in it.)
> BTW, where do you live nowadays, Robert? I'm thinking of doing a
> postdoc in the US next year, but I'm not sure yet where will I end up.
Right now I'm in Seattle, but things are very much up in the air
as to if and where Robiobotics may end up. It could be Reno or
perhaps even Quebec.
Best,
Robert
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