From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Thu Dec 28 2000 - 10:56:04 MST
CYMM ASKS:
> But Robert, fruit flies are relativerly shortlived, postmitotic
> critters that don't run into the problems that longlived creatures with
> more or less permanent mitotic tissues face.
True, I've not noticed anyone claiming that flies dye from cancer.
Such are the risks of self-renewal that solving one problem creates
another.
> What'll happen to the material that's shunted away from Kreb's Cycle...???
> what sort of degradation will it undergo... and are organisms like us
> prepared to deal with such??? would we see an increase in browning
> reactions etc.... ??? Which won't be debilitating in a fruitfly...because
> of timescales...but will in us.
The most recent information I've seen is that they don't currently
know what molecule the gene transports (they are working on figuring
that out). My suspicion is that it may be something that feeds
into the mitochondrial respiratory chain in such a way that
it results in a greater production of free radicals. So by blocking
cellular absorption of that nutrient, you may (a) be forcing the
cells to burn only the "cleanest" fuel available; or (b) be forcing
the cells to run "leaner", producing less overall pollution (free
radicals). Whatever the molecule is that isn't getting used is,
it probably gets recycled through a less damaging pathway or simply is
excreted. Or the molecule may end up being used, just at a slower
rate -- the scientists said the activity of the gene was only
"partially" blocked, and that it appeared that knocking the gene
out entirely would shorten lifespan (perhaps because the flies
are really starving).
If the cells are running lean, they may have a lower circulating
glucose level, therefore there would be a decrease in browning
(protein glycation) reactions. I don't know enough about fly
physiology to know the degree to which various organs do what
ours do (i.e. our liver breaking down glycogen to produce
circulating sugar for muscle or brain activity). We not only
need to know what molecule(s) the gene transports but also
the tissues in which it is active. As I think I mentioned
previously, using this approach in humans may be difficult
if we produce a drug that blocks the activity of that gene
in humans but that turns out to make you feel hungry all the
time (as people on CR generally do).
Robert
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