[extropy-chat] where to go with supplementation in a post-Nick-Lane world ?

[Robert Bradbury]

On 9/25/06, Ensel Sharon <user at dhp.com> wrote:

>
> Is that the goal ?  Is the goal an absolute reduction in oxygen
> consumption ?  Or is it a reduction in oxygen consumption relative to
> supply?


There is "plenty" of supply (if there isn't your body will force you to
breathe faster).

Scientists dealing with longevity and the antioxidant theory of
> aging, etc., speak of an "athlete paradox" wherein high levels of fitness
> and athletic output seem to prolong longevity, and yet it is clear that
> there is a quite marked increase in oxygen use.


Much of the O2 consumption in athletes goes to the muscles which should be
considered "special" tissues as they were designed to be able to support
high O2 consumption (muscle cells, unlike almost all other cells in the
body, can be considered to an extent "multi-nuclear" and therefore
"multi-genomic" -- so damage to individual genomes in muscles (from free
radicals) are less likely to result in cell death (at least that is my
current thinking).

Athletes channeling O2 and glucose to the muscles are probably saving their
other tissues from being "aged" by them.  The only exception to this would
be the few athletes which must maintain very high caloric intakes (4000+
calories/day) for decades -- I don't know whether this has been shown to
increase longevity -- I would strongly doubt it due to the excess work load
placed on the digestive tract.  But as far as I'm aware this is relatively
unstudied.

The book I mentioned speaks of oxygen traveling through the respiratory
> chains of mitochondria, and becoming "backed up" (for lack of a better
> term, and for lack of a deeper understaning on my part) because no further
> ATP (or heat) is needed, and it is there, in the mitochondria that the
> free radicals "leak".


This is relatively accurate (though simplified).  The problem is the
relative ratio of CoQ10 to downstream electron acceptors (which are
unoccupied) in the mitochondrial respiratory chain.  The longer CoQ10 is
sitting around with extra electrons the greater the probability that it will
transfer electrons to oxygen producing superoxide.

Further, it is there, in unprotected (relative to nucleic) mitochondrial
> DNA that the free radicals do their damage.  The nucleus, it would seem,
> has a fair amount of protection against both free radical damage and copy
> errors (again, relative to mito DNA) ...


This is an open question.  You have to bear in mind genome redundancy.  You
have hundreds of copies of each mitochondrial genome in a cell -- damaging
one doesn't do much harm.  You only have 2 (or 1 in the case of X|Y) copies
of your nuclear genome -- damage those and you have much larger problems.
So mitochondrial genomes could (and probably do) sustain much higher levels
of accumulated damage.  But nature has probably "balanced" the investment in
defenses and repair such that nuclear and mitochondrial DNA go bad at
relatively the same rate.  (Studies have proven that mitochondrial DNA
damage accumulates with age just as cancer demonstrates that horribly
pathogenic mutations are occurring in the nuclear DNA.)

... and so perhaps this line of thought will not be as benefical as you
> think, because if this new wrinkle in the antiox theory of aging bears any
> fruit, it is not nucleic DNA that you need to worry about as much as mito
> DNA.


I'm well aware of both  theories (they are formally known as the somatic
mutation theory of aging and the mitochondrial DNA damage theory of aging).
I'm currently of the opinion that the somatic (nuclear) DNA mutation problem
is of greater consequence than the mitochondrial DNA mutation problem.

Which kind of goes back to my original question:  if you are abreast of
> these developments (which may in fact be completely
> wrong/broken/etc./dontshootthemessenger)


Oh, on the ExI list  we don't shoot the messenger...  We just keel haul
them.  Then if they survive that we dismantle their body (the atoms from
poorly informed messengers can clearly be used for something better) being
sure we have extracted the information content from their brain so we can
make a million or so copies of said messenger and run them in basement
simulations (i.e. simulations running in simulations running in
simulations).  But unlike in The Matrix, where most people don't know they
are running in a simulation, *we* make sure poorly informed messengers
*know* they are running in a basement simulation *and* that there is no way
out (if you happened to find a way to "die", we'd just restart the
simulation).  But I digress...

are they causing you to rethink the entire "supplement anti-ox to prevent
> nucleic free-rad damage" ?
>
> It would seem not.
>

I think there are some things which may be of limited benefit and am
reasonably sure we don't fully understand things well enough to know what
they are (resveratrol and metformin consideration are products of the last
3-5 years of research and a much better understanding of what is really
going on).  But I am completely convinced that the best solutions will
involve engineering the genome so aging happens extremely slowly or not at
all.  I think we are relatively close to having both the technology and
engineering capabilities to do this.  So I'd *much* prefer to see people who
are investing their money in supplements [1] instead investing it in
companies that would be engineering non-aging genomes.

Robert

1. The amount of money spent on supplements which for the most part only
provide marginal benefits could fund thousands of researchers focused on
really fixing the genome.
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