From: Aubrey de Grey (ag24@gen.cam.ac.uk)
Date: Wed Apr 30 2003 - 14:38:11 MDT
Robert Bradbury wrote:
> The bottom line from my perspective is that if the cell wants to use
> H2O2 as a signaling molecule it will do so and taking all the Vitamin E
> and C in the world isn't going to prevent that. (Which isn't to say
> that Vitamin E might be highly useful to keep cholesterol from becoming
> oxidized and contributing to the formation of plaques). It seems
> unlikely that antioxidants are going to impact much on oxidative damage
> to DNA (and therefore cancer and some aspects of aging).
Right. This is the prime example of my contention that what will work
best against aging is reversal of accumulated damage, rather than any
attempt to pre-empt the formation of that damage by messing about with
bioactive molecules. See various of my recent publications.
Ramez Naam wrote:
> It's strange, though, that up-regulation of endogenous anti-oxidants
> /does/ slow aging. We know of a couple fruit fly models and at least
> one mouse model where the organisms have been genetically engineered
> to have higher levels of superoxide dismutase or catalase, and have
> (apparently as a result) had slower aging, longer mean and maximum
> lifespan, and greater resistance to stress.
>
> In the mouse model, the catalase is specifically targeted to the
> mitochondria. The fact that upregulating endogenous anti-oxidants in
> the mitochondria extends life seems to support the mitochondrial free
> radical theory of aging.
I confess I was extremely surprised at the mitochondrial catalase result
-- not least because it seems to go against the argument that Robert
gives above and with which I agree. I'm less concerned about successes
in flies and worms, because there the rate of free radical production is
really high and the pathways involved in translating this into aging
are probably a lot more simple and direct, more important than subtle
signalling stuff. My reading of the mitochondrial catalase result is
that this is a (rare, in mammals) similar case, where one is modulating
something that has so direct an effect on aging that the signalling
issue is somehow sidestepped (very much as Robert wrote in his second
post). But beware -- it may only work in lab mice, as CR seems to.
Aubrey de Grey
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