Re: caloric restriction

From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Fri Apr 12 2002 - 07:45:03 MDT


On 11 Apr 2002, Mike Linksvayer wrote:

> Two ideas/questions: Could metabolism be more efficient
> rather than lower?

Sure. There seem to be indications that when electron
transport chain in the mitochondria gets overloaded,
i.e. blocked in the downstream components because
they are already "working", that the upstream components
may start to produce more free radicals.

So a more "efficient" metabolism is one where the
overall flux never overloads the chain. I.e. when
you have to hand off your "product" to someone there
is always someone available to take it.

In contrast a "lower" metabolism is one where the
overall transport of energy through the system is
less. What would really seem to matter is the
electron flux/protein. You could make it more
efficient by simply having more mitochondria
available so that there is a lower probability
that individual mitochondria will develop traffic
jams that lead to free radical production. Of
course since the production and breakdown of
mitochondria consumes energy there has to be
"optimal" production point in this system.

> Could lower metabolism be an effect of CR, but not
> a/the life extension mechanism?

Perhaps, but things seem to be leaning in the direction
that metabolism produces free radicals, free radicals
damage DNA, damaged DNA decreases longevity.

> Human metabolism varies quite a bit among individuals

In terms of whether you store or burn calories yes,
but not in terms of absolute body temperature.
The core "metabolism" seems to be relatively fixed.

> (and individuals "practicing CR", though there's no
> rigorous definition that), but I haven't heard of any
> correlation with longevity.

You want to consider that several very long lived species
are not homeotherms. These include tortoises, lobsters,
giant clams and perhaps rockfish.

There is definately evidence that as you raise the
operating temperature of the species, it becomes
increasingly difficult to preserve the genome in
a reliable state. One can compensate for this
by increasing the G-C content of the genome over
evolutionary time but this is something that only
occurs gradually and has definate limits (running
into the constraints of the genetic code).

[Mike, if you have Ed's direct email address could you send
it to me offlist? Thanks.]

Robert



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