Free Radicals, more constraints

Edward Krug 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 
radical scavangers.

	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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