X-Message-Number: 14424
Date: Thu, 07 Sep 2000 05:32:08 -0400
From: Paul Wakfer <>
Subject: Re: #14420 - Oxidation theory of aging, etc
References: <>

> Message #14420
> Date: Wed, 06 Sep 2000 00:34:11 -0400
> From: James Swayze <>
> Subject: Re: Oxidation theory of aging, Greg Fahy, Please chime in!

Please note that a certain scientist has many times before requested,
and recently made clear to me once more that he still wishes to remain
only remotely linked to anything involving cryonics for the forseeable
future.
While I have been guilty of violating this in the recent past (partly
because I thought that it was no longer extant) I plan not to do so
again and I ask that everyone please refrain from mentioning his name in
any cryonics related context or publication.

[snip]


> The long and short of the above information and other pertaining to 
oxidation's

> contribution to aging paints a bleak picture indeed. I mean that if oxidation 
is
> the main cause

All *causes* must be classified as to "primariness". Oxidation is only a
cause of any damage in as much as there are insufficient preventative or
repairing chemicals in the right place at the right time. The generation
of such chemicals is more fundamentally up to our genes.

> and at the same time so tied to processes we cannot change

"Cannot change" is an entirely *relative* statement. In time and with
the right methods almost everything can be changed and enhanced even in
a fully developed human.

> then
> aging is not curable at least via this avenue. We can hardly shut down the
> mitochondria.

We do not need to. The ratio of energy to free radical output can be
increased (a combination of acetyl-l-carnitine and phenylbutyl nitrone
has been shown to do just that in older individuals) and the ability of
mitochondrial free radicals to cause damage can be decreased (see
below).

> At the Alcor conference in June Greg Fahy disputed the oxidation

> cause of aging theory and though I can't remember the details of his argument 
now

> it made sense to me at the time. He also put it that it was one if his pet 
peeves

> for the same reason I stated above in that if it is so then our hands are tied
> and he did not seem then to accept such a defeatist position. Greg if you are

> lurking could you please present your position on the matter again, here? 
Thanks.

Greg does not read CryoNet and will not likely be answering your message
except possibly through the intervention of someone else.

Unfortunately, I was not at the Alcor conference to see/hear the details
of Greg's talk. As far as intra (cytosolic/nuclear) and extra cellular
oxidation, I would agree that it is not a major factor in human maximum
longevity per se at the present time, although it is clearly a major
factor in individual and average human longevity extension by means of
disease and decline prevention. In addition, since free radicals
increase the rate of shortening of the telomeric ends of DNA, for those
situations where this becomes a factor limiting longevity (possibly
certain current diseases - AIDS - and eventually everyone, if maxiumum
longevity is extended sufficiently) their general reduction will also
become a factor involved in any addition increase in maximum longevity.

However, a current leading theory of aging, "The Mitochondrial Free
Radical Theory of Aging", recently expounded in a book by Aubrey de Grey
makes an excellent case that free radical damage to mitochondrial DNA
(not nearly as protected or as repairable as nuclear DNA) may be the
major determinant of human longevity. The catalase and SOD mimetics used
on the nematods in the recent experiments are mainly mitochondrial
antioxidants and generally ones which cannot be augmented in the
mitochondria by any direct means in humans. As I recall there was
already a much earlier experiment where fruit flies were genetically
altered to upregulate their SOD production and this doubled their
lifespan.

There are several potential avenues by which mitochondrial free radical
production or its damaging effects may be reduced. Short term proven
possibilities are the use of vitamin E, alpha lipoic acid, CoQ10, and
the (yet unavailable as a supplement) spin-trap phenylbutyl nitrone
(PBN), the last of which has been proven to extend maximum lifespan in
mice. Caloric restriction also definitely decreases the free radical
load on mitochondria and has been shown to increase maximum lifespan in
every species tested. In the longer run new mitochondrial antioxidant
drugs may be brought forth, and the genes for the 13 remaining proteins
which are generated by the mitochondrial DNA may be migrated into the
more protected cell nucleus where most of the other mitochondrially
needed proteins/enzymes have already been transferred over the ages by
evolution.

Finally, oxidation is a necessary part of the non-enzymatic
glycosylation (glycation) process by which damaging advanced glycation
endproducts (AGEs) build up quickly in diabetics (a model of accelerated
aging) and more slowly and inexorably in everyone, to cause
cross-linking and intracellular damage by attaching to receptors. There
are ways (again including calorie restriction) to reduce the rate of
glycation in order to give the body more time to metabolize their
damaging products, and a new anti-AGE, anti-crosslinking product ALT-711
is almost ready to begin phase 3 clinical trials.

The subject matter of oxidation (free radical) damage is extremely large
and I have attempted to merely touch lightly on some of the high points
here.


-- Paul --

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