[extropy-chat] AGING: real progress

Robert J. Bradbury bradbury at aeiveos.com
Sun Feb 22 16:39:10 UTC 2004


We seem to be in relative agreement with the similarity of genetic
programs in eukaryotes as well as the "all bets are off" perspective
when one goes from unicellular or small multicellular (potentially
short-lived) organisms to larger longer lived organisms.

So clearly the extrapolation of small, short-lived to large, long-lived
needs to be resolved.  I do not believe that will be easy.

I would grant that less apoptosis (p66 -/-) could easily extend lifespan.
The next question I would ask is whether such mice have a higher rate
of death from cancer?  If so this would imply that short lived animals
may be on the same balance as longer lived animals -- increased apoptosis
results in increased cell death which leads to aging, lack of apoptosis
leads to increased cancer rates that kill you via another path.

This is an important question because it involves whether or not
short-lived and long-lived species are on the same cancer vs. aging
tradeoff or on different paths.

> Although Warner mentions his ideas in the context of models of accelerated
> aging, I tend to see the delayed aging witnessed in p66 mice as similar.
> You can also easily extrapolate these models into Werner's syndrome.

Be very careful with linking these two (p66 and WS).  p66 may be
involved in the apoptosis pathway which if successful may prevent
the development of cancer but would require a complementary program
in stem cell development to provide replacement cells for cells lost
due to apoptosis.  WS is very different as I believe the WS gene is
an exonuclease meaning that it is going to corrupt the DNA code
during any repair process.

In short, the decision is:
a) Do I kill cells that have sustained damage -- hoping that new cells
   derived from stem cells will take over their functions?
b) Do I try to repair cells even though I may be producing a corrupted
   genome in those cells in the process?  (And of course the corrupted
   genome has greater chances of causing problems in the future.)

I do not believe that nature has developed a good genetic program
that resolves these questions.  Without the view that genomes are
genetic programs with patches on top of patches on top of patches
I believe it will be difficult to fully understand them.


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