Free Radicals, more constraints
kruged at ESSEX.HSC.COLORADO.EDU
Fri Jan 27 18:23:45 EST 1995
There are four concepts I wish to include in the ongoing free radical
First is that the various free radical scavangers have
preferential cell comparatments which limit the interactions they can
affect. Vit. E for instance is preferentially located in the lipid
membranes and hydrophobic areas, while Vit. C tends to localize in the
hydrophylic regions. The number and type of free radical interactions
in arm's reach is consequently reduced. A number and variety of
antioxidants may be necessary to cover all the ongoing interactions.
Second, the handshake each free radical scavanger requires for
accepting the wayward electrons is probably somewhat unique. There
probably is not a scavanger "for all seasons", and therefore a panoply of
antioxidants may be necessary to cover all free radical reactions.
Third, although scavangers may intercept much of the free
radical "bombs" it is a rare biological system which is 100% efficient.
In enzymology disulfide bonds are broken or oxidized during some
purification steps and must be reduce or rejoined specifically to regain
enzymatic function. Although scavangers may prevent some oxidation they
probably do little to repair damage once it happens.
Fourth, time and time again nature has been shown to be even more
concervative than American Republican Talk Show Hosts. The mechanisms
evolved in the early sexually reproducing multicellular organisms for
insuring a turnover of the members of the adult population have probably
been retained over the millions of subsequent years. These probably have
been modified, but probably retained in some form. Add to these new
mechanisms as evolution increased the complexity of the organisms. For
there to be more than five independent processes contributing to finite
lifespan would surprise me little.
Summary? The elucidation of the free radical based organism
damage will reach a point where only marginal improvement in some aspect
of old age vitality is achieved by intercepting the free radicals.
Replacement of declining hormone levels or trophic factors or increasing
the number of controled cell doublings, or invoking the lost capacity of
regeneration as in amphibians or some other venues will have to be
employed to extend healthy lifespan.
To think that just because a remedy dosen't produce a dramatic
result in a complex system that it is not involved is faulty logic, just
as saying that since a five legged stool dosen't fall down when you
take any one of them away proves that the legs do not hold the stool up.
Conclusion/suggestions? Caloric restriction to date has produced
the most dramatic life extension, but it achieves only an extension.
This method has revealed that certain diseases are coincidental with ageing,
but not essential. Although this old observation may not lead to a cure,
it is extremely important for ageing theory purposes. The question
becomes what continues to degrade the organism in the reduced calorie
nutritional condition. Since not all free radicals derive from leaky
mitochondria or other conditions found in the fat and sassy organism the
best place to look for a larger life extension effect would be in the
calorically restricted orgamism using an array of antioxidants and free
I appologize for insulting anyones intelligence, but the
discussion seemed to be getting too symplistic.
Edward C. Krug Ph.D. E-mail= kruged at essex.hsc.colorado.edu
303-270-7234 (vox), 303-270-8681 (fax) Univ. of Colorado Med. School
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