From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Wed Apr 10 2002 - 06:23:23 MDT
On 9 Apr 2002, Mike Linksvayer wrote:
> Quoting from a cite posted to the CR list today:
>
> Initial theories that CR acted mainly through retarding growth
> and development, reducing the metabolic rate and body fat have not
> been born out. CR seems to modify biologic activities at every
> level, affecting physiologic, molecular, and genomic processes
> [45]. More specifically, CR reduces insulin-like growth factor 1
> levels [46], reduces oxidative stress [47] and bolsters DNA repair
> and genomic stability [48, 49]. Regarding the latter, Guarente's
> group [50] have just identified a mechanism in yeast through which
> CR might mediate its effects. CR boosts Sir2, a protein needed for
> a phenomenon called silencing which turns genes off at particular
> chromosomal regions.
>
> CR doesn't appear to work by slowing down metabolism, though it is
> systemic, details unknown as noted.
I'd disagree. I'm moderately certain that its been shown in
multiple studies, including primate studies, that CR lowers
body temperature (and so therefore metabolism must be lower).
I suppose one could split hairs here and propose that only
disposal of excess mitochondrial hydrogen ion gradient
(that contributes to heat production) is lower and not
actual "metabolism", but thats a very fine distinction.
In either case the result is lower free radical production
which would contribute to lower DNA damage.
The gene silencing mechanism would imply that the genes are
likely to be wrapped around histones which would shelter the
DNA to some extent from free radical damage. Of course there
will be a big hurdle in extrapolating the yeast work to higher
organisms because single celled organisms will want to carry
on even in the presence or DNA damage while multi-cellular
organisms may want to eliminate cells with such damage to
reduce the chance that they will become cancerous.
[Mike, if you have the full post to the CR list with references,
I'd appreciate a copy of it. Thanks.]
Robert
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