Another Negative Antioxidant Life Span Study in Rodents
Steve Harris
atherosclerosis prevention, which doesn't apply to rodents. So this doesn't
mean antioxidant supplementation is necessarily worthless in the average
human. But this and many other studies put a money wrench into the theory
that somehow antioxidants interfere with the basic aging process itself.
There is no really good evidence that they do. At least, not in mammals.
Ann N Y Acad Sci 1998 Nov 20;854:352-60
The effect of long-term dietary supplementation with antioxidants.
Meydani M, Lipman RD, Han SN, Wu D, Beharka A, Martin KR, Bronson R, Cao G,
Smith D, Meydani SN.
JM USDA-Human Nutrition Research Center on Aging at Tufts University,
Boston, Massachusetts, USA. meyda...@hnrc.tufts.edu
The impact of diet and specific food groups on aging and age-associated
degenerative diseases has been widely recognized in recent years. The modern
concept of the free radical theory of aging takes as its basis a shift in
the antioxidant/prooxidant balance that leads to increased oxidative stress,
dysregulation of cellular function, and aging. In the context of this
theory, antioxidants can influence the primary "intrinsic" aging process as
well as several secondary age-associated pathological processes. For the
latter, several epidemiological and clinical studies have revealed potential
roles for dietary antioxidants in the age-associated decline of immune
function and the reduction of risk of morbidity and mortality from cancer
and heart disease. We reported that long-term supplementation with vitamin E
enhances immune function in aged animals and elderly subjects. We have also
found that the beneficial effect of vitamin E in the reduction of risk of
atherosclerosis is, in part, associated with molecular modulation of the
interaction of immune and endothelial cells. Even though the effects of
dietary antioxidants on aging have been mostly observed in relation to
age-associated diseases, the effects cannot be totally separated from those
related to the intrinsic aging process. For modulation of the aging process
by antioxidants, earlier reports have indicated that antioxidant feeding
increased the median life span of mice to some extent. To further delineate
the effect of dietary antioxidants on aging and longevity, middle-aged (18
mo) C57BL/6NIA male mice were fed ad libitum semisynthetic AIN-76 diets
supplemented with different antioxidants (vitamin E, glutathione, melatonin,
and strawberry extract). We found that dietary antioxidants had no effect on
the pathological outcome or on mean and maximum life span of the mice, which
was observed despite the reduced level of lipid peroxidation products,
4-hydroxynonenol, in the liver of animals supplemented with vitamin E and
strawberry extract (1.34 +/- 0.4 and 1.6 +/- 0.5 nmol/g, respectively)
compared to animals fed the control diet (2.35 +/- 1.4 nmol/g). However,
vitamin E-supplemented mice had significantly lower lung viral levels
following influenza infection, a viral challenge associated with oxidative
stress. These and other observations indicate that, at present, the effects
of dietary antioxidants are mainly demonstrated in connection with
age-associated diseases in which oxidative stress appears to be intimately
involved. Further studies are needed to determine the effect of antioxidant
supplementation on longevity in the context of moderate caloric restriction.
Publication Types:
Review
Review, Tutorial
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CBI
"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
news:a6h84i$i63$1...@slb4.atl.mindspring.net...
> Probably the main impact of antioxidant supplmentation in humans will be
in
> atherosclerosis prevention, which doesn't apply to rodents. So this
doesn't
> mean antioxidant supplementation is necessarily worthless in the average
> human. But this and many other studies put a money wrench into the theory
> that somehow antioxidants interfere with the basic aging process itself.
> There is no really good evidence that they do. At least, not in mammals.
>
I'm sure you will correct me if I am wrong, but don't rodents make ascorbic
acid by their own metabolism? If this is the case then that provides another
fundamental difference which would make rodent studies on the topic not very
applicable to humans. Not that I disagree with your conclusions.
--
CBI, MD
Eggs Pancakes Syrup Toast Coffee
life, but did improve quality of life...
GOOD!
________________________
THUS SAYETH WithBACON
Nelson J. Navarro
"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
news:a6h84i$i63$1...@slb4.atl.mindspring.net...
in
> atherosclerosis prevention, which doesn't apply to rodents. So this
doesn't
> mean antioxidant supplementation is necessarily worthless in the average
> human. But this and many other studies put a money wrench into the theory
> that somehow antioxidants interfere with the basic aging process itself.
> There is no really good evidence that they do. At least, not in mammals.
>
Of course it may be simply that no one has tried the right antioxidant yet.
If neither NtBHA, (R+)-ALA nor any of M.P. Murphy's mitochondrial specific
antioxidants are shown to have any effect on aging, then I'll probably come
over to your camp.
Tom Matthews
> Probably the main impact of antioxidant supplmentation in humans will be in
> atherosclerosis prevention, which doesn't apply to rodents. So this doesn't
> mean antioxidant supplementation is necessarily worthless in the average
> human. But this and many other studies put a money wrench into the theory
> that somehow antioxidants interfere with the basic aging process itself.
> There is no really good evidence that they do. At least, not in mammals.
Except that there are virtually no such studies on "modern" antioxidants
such as PBN, NtBHA, RLA, carnosine, N-acetyl-L-carnosine, etc. Some of
which, granted, may have effects by means other than being antioxidants.
Frankly, I don't much care *why* something extends my life, just so long
as it does. In addition, if some "cocktail" will cause me to gain an
extra 10-15 years then I also don't care if it has reduced my "basic
aging rate" or not (in however arbitrary fashion you wish to define that
term for an individual).
--Tom Matthews
MoreLife for us all - http://morelife.org
Reality based tools for More Life in quantity & quality
Max Watt
> Of course it may be simply that no one has tried the right antioxidant yet.
> If neither NtBHA, (R+)-ALA nor any of M.P. Murphy's mitochondrial specific
> antioxidants are shown to have any effect on aging, then I'll probably come
> over to your camp.
PBN is a very potent anti-oxidant, and has been shown to extend rodent
life spans. NtBHA appears to be the active moiety of PBN, so one
would expect it to extend rodent life span too. For ALA the
possibility is theoretically justified, as the mechanism is thought to
be the same a PBN/NtBHA.
Nelson J. Navarro
"Max Watt" <maxwa...@yahoo.com> wrote in message
news:870a5d01.02031...@posting.google.com...
> "Nelson J. Navarro" <nnav...@adelphia.net> wrote in message
news:<QN0j8.6511$RB.14...@news1.news.adelphia.net>...
>
> > Of course it may be simply that no one has tried the right antioxidant
yet.
> > If neither NtBHA, (R+)-ALA nor any of M.P. Murphy's mitochondrial
specific
> > antioxidants are shown to have any effect on aging, then I'll probably
come
> > over to your camp.
>
> PBN is a very potent anti-oxidant, and has been shown to extend rodent
> life spans.
If I recall correctly, its effect on life span seems to be real, but not
very robust.
NtBHA appears to be the active moiety of PBN, so one
> would expect it to extend rodent life span too.
That's certainly what we're hoping for.
What I find encouraging is the fact that NtBHA seems to be much more
effective than PBN in vitro.
For ALA the
> possibility is theoretically justified, as the mechanism is thought to
> be the same a PBN/NtBHA.
Well, it appears they are similar in some ways (if I recall correctly, ALA
and NtBHA both restore/protect aconitase in the mitochondrial matrix), and
different in others (NtBHA seems to enhance proteasome activity, but I've
not seen any studies indicating the same for ALA; also, I believe NtBHA
directly quenches superoxide, but not ALA, although I believe DHLA does).
Regards,
Nelson Navarro
Thomas Carter
> atherosclerosis prevention, which doesn't apply to rodents. So this doesn't
> mean antioxidant supplementation is necessarily worthless in the average
> human. But this and many other studies put a money wrench into the theory
> that somehow antioxidants interfere with the basic aging process itself.
> There is no really good evidence that they do. At least, not in mammals.
>
>
>
> Ann N Y Acad Sci 1998 Nov 20;854:352-60
>
>
It certanly is a challenge for supplement users to explain why they
expect great benefits from antioxidants when their distant cousins see
very few. The full text of the above article references a few
beneficial studies, but no real headliners. The N Y Academy of Science
has now made its full text free on line and their format in which
similar articles are grouped together in one volumn makes for some
great browsing. For instance this article is in a volumn practicle
interventions to slow the aging process. It is the best collection I
have seen, and I expect to be reading it for the next week or month.
Just paste Ann N Y Acad Sci in the medline search box, click on any
article, Then the Academy icon, then archives, then 1998, then volumn
854.
Also, the NEJM and "Circulation" have now made one year old archives
available in full text so I have updated my search string for full
text articles.
Here 'tis.
(("Am J Clin Nutr" AND 1999:2000[dp]) OR ("Am J Respir Cell Mol Biol"
AND 1997:2001[dp]) OR (Ann N Y Acad Sci AND 1998:2100[dp]) OR
("Biochem J" AND 1996:2000[dp]) OR ("Biol Reprod" AND 1998:2000[dp])
OR ("Blood"[ta] AND 1996:2000[dp]) OR (BMJ AND 1994:2001[dp]) OR
(“Circulation”[ta] AND 1995:2001/03[dp]) OR (“Clin
Cancer Res” AND 1999:2001[dp]) OR ("Curr Biol") OR
("diabetes"[ta] AND 1998:2100/01[dp] OR ("FASEB j" AND 1998:2000[dp])
OR ("endocr rev" AND 1997:2000[dp]) OR ("endocrinology" AND
1997:2000[dp]) OR ("EMBO J" AND 1997:2000[dp]) OR ("Genetics"[ta] AND
1998:2000[dp]) OR ("J Appl Physiol" AND 1997:2000[dp]) OR ("j biol
chem" AND 1995:2000[dp]) OR ("J Cell Biol" AND 1997:2001/06[dp]) OR
("J Clin Endocrinol Metab" AND 1998:2000[dp]) OR ("J Clin Invest" AND
1996:2100[dp]) OR ("J Endocrinol" AND 1997:2000[dp]) OR ("J Exp Biol"
AND 1992:2010[dp]) OR J Korean Med Sci AND 1996:2010[dp]) OR ("J
Neurosci" AND 1997:2000[dp]) OR ("J Nutr" AND 1997:2000[dp]) OR ("J
Virol" AND 1998:2000[dp]) OR (medline pmc [sb]) OR ("Mol Biol Cell"
AND 1997:2001/06[dp]) OR ("Mol Endocrinol" AND 1997:2000[dp]) OR (N
Engl J Med AND 1993:2001/03[dp] OR ("Proc Natl Acad Sci U S A" AND
1996:2001[dp])) AND (Review[pt])
See my post at the url below for a brief explanation on how to use
and customize the search string for your own needs. Or search
sci.life-extension for my name and the words; "we all like".
Michael C Price
Big deal.
Try cofactors such as the B-vitamins and minerals
Cheers
Michael C Price
Dave
Steve Harris wrote:
> Probably the main impact of antioxidant supplmentation in humans will be in
> atherosclerosis prevention, which doesn't apply to rodents. So this doesn't
> mean antioxidant supplementation is necessarily worthless in the average
> human. But this and many other studies put a money wrench into the theory
> that somehow antioxidants interfere with the basic aging process itself.
> There is no really good evidence that they do. At least, not in mammals.
Interesting study. I would be interested to know whether you feel that
anti-oxidant supplementation may be of value during periods of increased
oxidative stress, such as exercise in particular, or in general have any
benefit in extending the quality of life or *average* life span in
humans. You mention the preventative use of anti-oxidants in
atherosclerosis; what about the preventative use in other degenerative
diseases, which, while amelioration of such may not directly interrupt
the aging process, would certainly seem to *indirectly* do so (at least
in so far as *median* life span is concerned). I notice that the
authors did not observe any increase in median life span, but did
mention earlier "reports" to the contrary.
Dave
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Dave
CBI wrote:
The supplemental anti-oxidants fed to the mice in the study did not
include vitamin C; at least, I did not see any mention of such.
Dave
> --
> CBI, MD
Dave
Tom Matthews wrote:
> Steve Harris wrote:
>
>> Probably the main impact of antioxidant supplmentation in humans will
>> be in
>> atherosclerosis prevention, which doesn't apply to rodents. So this
>> doesn't
>> mean antioxidant supplementation is necessarily worthless in the average
>> human. But this and many other studies put a money wrench into the theory
>> that somehow antioxidants interfere with the basic aging process itself.
>> There is no really good evidence that they do. At least, not in mammals.
>
>
>
> Except that there are virtually no such studies on "modern" antioxidants
> such as PBN, NtBHA, RLA, carnosine, N-acetyl-L-carnosine, etc. Some of
> which, granted, may have effects by means other than being antioxidants.
> Frankly, I don't much care *why* something extends my life, just so long
> as it does. In addition, if some "cocktail" will cause me to gain an
> extra 10-15 years then I also don't care if it has reduced my "basic
> aging rate" or not (in however arbitrary fashion you wish to define that
> term for an individual).
Yeah, I'm quite pragmatic when it comes to the science of aging as well.
Dave
>
> --Tom Matthews
>
> MoreLife for us all - http://morelife.org
> Reality based tools for More Life in quantity & quality
>
Dave
Thomas Carter wrote:
> "Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message news:<a6h84i$i63$1...@slb4.atl.mindspring.net>...
>
>>Probably the main impact of antioxidant supplmentation in humans will be in
>>atherosclerosis prevention, which doesn't apply to rodents. So this doesn't
>>mean antioxidant supplementation is necessarily worthless in the average
>>human. But this and many other studies put a money wrench into the theory
>>that somehow antioxidants interfere with the basic aging process itself.
>>There is no really good evidence that they do. At least, not in mammals.
>>
>>
>>
>>Ann N Y Acad Sci 1998 Nov 20;854:352-60
>>
>>
>>
> Hi Steve and all,
> It certanly is a challenge for supplement users to explain why they
> expect great benefits from antioxidants when their distant cousins see
> very few. The full text of the above article references a few
> beneficial studies, but no real headliners. The N Y Academy of Science
> has now made its full text free on line and their format in which
> similar articles are grouped together in one volumn makes for some
> great browsing. For instance this article is in a volumn practicle [sic]
> interventions to slow the aging process. It is the best collection I
There is a whole volume dedicated to "practical interventions to slow
the aging process?" Wow. Sounds just what I've been looking for;
thanks for the info!
Dave
Peter H. Proctor
>From: "Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com>
>Subject: Another Negative Antioxidant Life Span Study in Rodents
>Date: Sun, 10 Mar 2002 20:20:08 -0700
>Probably the main impact of antioxidant supplmentation in humans will be in
>atherosclerosis prevention, which doesn't apply to rodents. So this doesn't
>mean antioxidant supplementation is necessarily worthless in the average
>human. But this and many other studies put a money wrench into the theory
>that somehow antioxidants interfere with the basic aging process itself.
>There is no really good evidence that they do. At least, not in mammals.
Here is the key Phrase:
." These and other observations indicate that, at present, the effects
>of dietary antioxidants are mainly demonstrated in connection with
>age-associated diseases in which oxidative stress appears to be intimately
>involved. "
This reflects the distinction between the "samll" and "large" theories
of oxidative stress and aging. The "Small" theory says that activated
species are involved in identifiable pathological processes which eventually
produce things like atherosclerosis and cancer. This is pretty well
established.
Most people eventually die from one of these things. So, the
role of oxidative stress in "aging" is clear, if perhaps indirect. OTOH,
the "strong" theory says that aging per se is somehow directly related to
oxidative stress. The evidence for this is much less clear.
Dr P
Peter H. Proctor
>From: "CBI" <00...@mindspring.com>
>Subject: Re: Another Negative Antioxidant Life Span Study in Rodents
>Date: Sun, 10 Mar 2002 22:56:16 -0500
>I'm sure you will correct me if I am wrong, but don't rodents make ascorbic
>acid by their own metabolism? If this is the case then that provides another
>fundamental difference which would make rodent studies on the topic not very
>applicable to humans. Not that I disagree with your conclusions.
Another issue is that reducing antioxidants often ( usually ? ) also act
as prooxidants. OTOH, PBN doesn't do this and can extend maximum lifespan.
Dr P
Peter H. Proctor
>From: "Nelson J. Navarro" <nnav...@adelphia.net>
>Subject: Re: Another Negative Antioxidant Life Span Study in Rodents
>That's certainly what we're hoping for.
>What I find encouraging is the fact that NtBHA seems to be much more
>effective than PBN in vitro.
NtBHA connects the Nitrone spin traps such as PBN with the nitroxide
spin labels such as TEMPO. The latter are quickly reduced to their
corresponding hydroxylamine "prodrug" forms in vivo. The "HA" in NtBHA stands
for hydroxylamine.
The hydroxylamine derivative reacts with superoxide to (re)generate
the nitroxide, which then acts as 1) a spin trap, 2) an SOD, or 3) a
competitive inhibitor of the reaction between superoxide and nitric oxide to
produce peroxinitrite ( an important mediator of pathogenesis ).
Dr P
Steve Harris
news:F61E23FA9FE4F761.72ECB283...@lp.airnews.net...
COMMENT:
Probably you're going to have to do more explaining than that. For the
audience here: "Spin trap" is generally used to describe PBN-type non-free
radical compounds containing nitrone:
C=N-->O
C
Here the arrow shows that both electrons in the bond are contributed by the
oxygen, giving the bond a formal charge separation (ie, it's a little bit
wierd).
Nitrones are not radicals but react with radicals to eat the extra radical
electron and form the corresponding nitroxide:
C-N-0'
C
Where ' stands for the "radical" or unpaired electron. These compounds
(TEMPO the example) are stable analogs of nitric oxide:
:N-O' where the nitrogen is bonded to two other things instead of just
sporting an electron pair as I've drawn it for NO'. Nitroxides, as stable
radicals, have an over-all molecular spin, and are used as spin-labels to
put a free radical on organics (some other bond in the molecule is used for
this, so the NO' stays unchanged), which allows them to be "seen" with
electron spin spectroscopy (ESR).
But now here you say that hydroxylamines
C-N-OH
C
can lose a proton to superoxide, regenerating the nitoxyl C2- N-O' But
you then call that a "spin trap". Nitroxides, being radicals, can form
spin-adducts with things like superoxide O2'- and in that sense "trap" the
radicals. And TEMPO has been used as a cerebral resuscitation drug, as has
PBN, so the general sponging of radicals is probably similar with these as
it is in NtBHA. But "spin trap" (not a radical) and "spin label" (a radical)
are used quite differently and not interchangably in the literature, as you
well know (I see your many patents on these things).
SBH
Steve Harris
news:3C8CBED2...@morelife.org...
> Steve Harris wrote:
>
> > Probably the main impact of antioxidant supplmentation in humans will be
in
> > atherosclerosis prevention, which doesn't apply to rodents. So this
doesn't
> > mean antioxidant supplementation is necessarily worthless in the average
> > human. But this and many other studies put a money wrench into the
theory
> > that somehow antioxidants interfere with the basic aging process itself.
> > There is no really good evidence that they do. At least, not in mammals.
>
>
> Except that there are virtually no such studies on "modern" antioxidants
> such as PBN, NtBHA, RLA, carnosine, N-acetyl-L-carnosine, etc.
COMMENT:
But that becomes an endless comment, because the combo of antioxidants used
today is never the one that will be in vogue tomorrow. The experiment
described was done to try to answer critics who always complained about
things like C and E being used alone. But if you use combos of vitamins and
minerals you now run into people saying it's not a good experiment because
it didn't include "PBN, NtBHA, RLA, carnosine, N-acetyl-L-carnosine, etc."
And if those are negative, something else will be brought up as being
necessary. As noted, this approaches religion. The premises are not only
data-free, they're data-proof.
SBH
Tom Matthews
Though not yet directly proven, all the benefits of PBN are likely to be even
more true for its active and non-toxic moiety, N-tert-butyl-hydroxylamine (NtBHA).
For a summary of the literature on this see:
http://morelife.org/lifespan/reaching/researchems/NtBHA.html
Tom Matthews
> In article <a6h84i$i63$1...@slb4.atl.mindspring.net> "Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> writes:
>
>>From: "Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com>
>>Subject: Another Negative Antioxidant Life Span Study in Rodents
>>Date: Sun, 10 Mar 2002 20:20:08 -0700
>>
>
>>Probably the main impact of antioxidant supplmentation in humans will be in
>>atherosclerosis prevention, which doesn't apply to rodents. So this doesn't
>>mean antioxidant supplementation is necessarily worthless in the average
>>human. But this and many other studies put a money wrench into the theory
>>that somehow antioxidants interfere with the basic aging process itself.
>>There is no really good evidence that they do. At least, not in mammals.
>>
>
> Here is the key Phrase:
>
>> " These and other observations indicate that, at present, the effects
>>of dietary antioxidants are mainly demonstrated in connection with
>>age-associated diseases in which oxidative stress appears to be intimately
>>involved. "
>>
> This reflects the distinction between the "samll" and "large" theories
> of oxidative stress and aging. The "Small" theory says that activated
> species are involved in identifiable pathological processes which eventually
> produce things like atherosclerosis and cancer. This is pretty well
> established.
>
> Most people eventually die from one of these things. So, the
> role of oxidative stress in "aging" is clear, if perhaps indirect. OTOH,
> the "strong" theory says that aging per se is somehow directly related to
> oxidative stress. The evidence for this is much less clear.
Thank you, Peter, for this excellent description of the differences. I
am in total agreement with this view. However, I also think that there
is reasonable evidence that many more specific pathologies than
athersclerosis and cancer can be inhibited and greatly put off the use
of diet and supplements. Some of these are merely quality of life
disabling, but others lead to early mortality which can be made later by
dietary means including supplements.
In these ways, by inhibiting many individual pathologies and life-quality
disabling conditions, dietary methods including supplements can have a
major benefit for both average life length and overall life quality.
Tom Matthews
COMMENT:
Nonsense! You are simply attempting to support a poorly designed study
by attempting to smear the critics. Lack of proof of a premise is not
proof of its falsity, which is what *you* appear to be implying! I say
*that* is more akin to religion!
I have already argued why the use of those three antioxidants in the
form given was likely to fail. This was in another message on another
thread (Supplement Cocktails [was Re: Oxidation/polymerization of
polyunsaturates (was Re: alpha lipoic acid eliminates wrinkles?) which I
notice you chose not to answer. Very frankly, it is almost as if the
researchers wanted to see a negative result on supplements to bolster
the establishment view, since I find it hard to believe that they were
that ignorant of the modern literature on the subject.
My argument that a well design set of supplements to cover all known
interactions and tendencies toward isolated, tissue-specific pro-oxidant
effects can still work to increase average lifespan and has not yet been
tested.
My comment about the "modern" antioxidants that I named was related to
possibilities of radically increasing life quality, extending average
lifespan, and possibly extending maximum lifespan.
I remind you that oxidation effects are known to cause accelerated
telomere shortening and that antioxidants (again in the right
combinations) may inhibit this shortening rate.
Finally, I am not talking about antioxidants merely. Another major area
are antiglycation dietary and supplemental methods. And then there are
cell differentiation inducing substances such as D3 and tributyrin which
have recently been discussed on sle. In general, there are a host of
chemical supplements many of which have been shown to have clear
beneficial effects (some in terms of life quality and others in terms of
specific pathology reduction) which are not necessarily related to any
antioxidant ability.
Peter H. Proctor
>From: Tom Matthews <t...@morelife.org>
>Subject: Re: Another Negative Antioxidant Life Span Study in Rodents
>Date: Fri, 15 Mar 2002 02:43:28 -0500
>Peter H. Proctor wrote:
>> This reflects the distinction between the "samll" and "large" theories
>> of oxidative stress and aging. The "Small" theory says that activated
>> species are involved in identifiable pathological processes which eventually
>> produce things like atherosclerosis and cancer. This is pretty well
>> established.
>>
>> Most people eventually die from one of these things. So, the
>> role of oxidative stress in "aging" is clear, if perhaps indirect. OTOH,
>> the "strong" theory says that aging per se is somehow directly related to
>> oxidative stress. The evidence for this is much less clear.
>..... However, I also think that there
>is reasonable evidence that many more specific pathologies than
>athersclerosis and cancer can be inhibited and greatly put off the use
>of diet and supplements. Some of these are merely quality of life
>disabling, but others lead to early mortality which can be made later by
>dietary means including supplements.
Agree. In fact, in a review, I make the point that " The term
free radical pathogenesis is perhaps redundant". This is because oxidative
stress is so intimately related to just about everything that makes tissues go
bad. As for suppliments, e.g., B12, folate, and B6 lower homocysteine,
which may exert ist effects on (say) atherosclerosis and alzheimer's by
generating active oxygen species.
Dr P
Dave
Steve Harris wrote:
> "Tom Matthews" <t...@morelife.org> wrote in message
> news:3C8CBED2...@morelife.org...
>
>>Steve Harris wrote:
>>
>>
>>>Probably the main impact of antioxidant supplmentation in humans will be
>>>
> in
>
>>>atherosclerosis prevention, which doesn't apply to rodents. So this
>>>
> doesn't
>
>>>mean antioxidant supplementation is necessarily worthless in the average
>>>human. But this and many other studies put a money wrench into the
>>>
> theory
>
>>>that somehow antioxidants interfere with the basic aging process itself.
>>>There is no really good evidence that they do. At least, not in mammals.
>>>
>>
>>Except that there are virtually no such studies on "modern" antioxidants
>>such as PBN, NtBHA, RLA, carnosine, N-acetyl-L-carnosine, etc.
>>
>
>
> COMMENT:
>
> But that becomes an endless comment, because the combo of antioxidants used
> today is never the one that will be in vogue tomorrow. The experiment
That is always true in science; we keep testing and retesting new
things, until we finally (and hopefully) stumble upon a drug(s) that "work."
I think your statement would have more relevance if all "anti-oxidants"
could be lumped together as sharing a single, common mechanism of
action, varying say, only by the degree of potency in which they exert
their effects. However, this is clearly not the case, as the compounds
mentioned above affect many biological parameters that are not likely
influenced by Vitamin C, E., etc.
Dave
Dave B
Yeah good point. And people don't normally live the cushy, stable lives of
lab rats. Try the experiment out on NY sewer rats instead. ;-)
<snip>
Nelson J. Navarro
> "Tom Matthews" <t...@morelife.org> wrote in message
> news:3C8CBED2...@morelife.org...
> > Steve Harris wrote:
> >
> > > Probably the main impact of antioxidant supplmentation in humans will
be
> in
> > > atherosclerosis prevention, which doesn't apply to rodents. So this
> doesn't
> > > mean antioxidant supplementation is necessarily worthless in the
average
> > > human. But this and many other studies put a money wrench into the
> theory
> > > that somehow antioxidants interfere with the basic aging process
itself.
> > > There is no really good evidence that they do. At least, not in
mammals.
> >
> >
> > Except that there are virtually no such studies on "modern" antioxidants
> > such as PBN, NtBHA, RLA, carnosine, N-acetyl-L-carnosine, etc.
>
>
> COMMENT:
>
> But that becomes an endless comment, because the combo of antioxidants
used
> today is never the one that will be in vogue tomorrow.
Well sure it does, but that's because science is progressing.
The computers manufactured five years from now will be better than the one I
have now; cars will be more sophisticated;
anti-diabetic drugs will be more effective, etc.; why wouldn't the same be
true of newly discovered antioxidants?
As evidence mounts that oxidative damage to mitochondria plays a significant
role in aging, and new compounds are discovered that protect mitochondria
much more effectively than "Vitamin E", for example, we will need to test
them before we say they won't work, no?
Regards,
Nelson Navarro
Steve Harris
> > COMMENT:
> >
> > But that becomes an endless comment, because the combo of antioxidants
> used
> > today is never the one that will be in vogue tomorrow.
>
> Well sure it does, but that's because science is progressing.
>
> The computers manufactured five years from now will be better than the one
I
> have now; cars will be more sophisticated;
> anti-diabetic drugs will be more effective, etc.; why wouldn't the same be
> true of newly discovered antioxidants?
"Progressing" means progressing from something that works to something that
works better, as with computers. Antioxidants basically don't "work" very
well, if at all in people, and never have (show me the study that they
lengthen life). The belief that they will one day is touching, but I'm
afraid it remains to be proven.
> As evidence mounts that oxidative damage to mitochondria plays a
significant
> role in aging, and new compounds are discovered that protect mitochondria
> much more effectively than "Vitamin E", for example, we will need to test
> them before we say they won't work, no?
COMMENT:
Yes. But until then, you have only a theory. And not a very good one. You're
made of more than just mitochondria.
I've given you the counter-theory here before. Free radicals are the signals
used by the body's inflammatory system, which is necessary for
infection-fighting, normal healing, and for fighting some (not all) kinds of
cancer. Free radicals (including deliberately produced ones like NO.)
aren't just garbage to be expunged in every possible way you can think of,
but rather instead are often important signals, not to be ignored. You can't
just willy-nilly shotgun them, and the system which uses them, out of
existence for long, without expecting to pay a price. Nature didn't give it
all of that complicated radical-producing and radical-sensing machinery to
you, for nothing.
How long can you shotgun the entire free radical signal pathways in your
body, and get away with it? Perhaps hours, if you're treating some really
bad and inappropriate inflammation, such as reperfusion injury. Maybe days,
if lucky. Not months or years, unless you'd like to live in a plastic
bubble. If anybody comes up with something that protects mitochondia from
free radicals they produce, if it is to be used for a life-time it's going
to have to be remarkable for its *specificity*, NOT its generality.
But I see that the dopey spirit of Pearson and Shaw is still alive and well
on at least one newsgroup.
Dave B
Dr. Packer, one of the world's leading researchers on antioxidants,
apparently feels differently. So do many other scientists who have looked
at the same data you have. What up with dat?
Knows All'@hotmail.com John 'Knows All
news:a6ugke$nfs$1...@slb7.atl.mindspring.net...
> Antioxidants basically don't "work" very
> well, if at all in people, and never have (show me the study that they
> lengthen life).
If antioxidants don't work, then why does your body have an antioxidant
system?
~ Antioxidant Supplements ~
http://info.naturalhealthperspective.com/antioxidants.html
"The Primary OBJECTIVE of taking a variety of the right antioxidant
supplements is NOT to create an antioxidant defense system; but rather to
boost your body's enzymatic antioxidant defense system (which consists of
glutathione reductase/peroxidase and other important antioxidant enzymes
like superoxide dismutase and catalase)." [25,26,29]
It is all a matter of definition. :-)
Nobody is shot gunning anything. It is simply a matter of boosting your
body's natural enzymatic antioxidant defense system.
Again, it is all a matter of vocabulary.
You can take measures to strengthen your immune system, your muscles, your
endurance, your heart, as well as your bodies detoxification's system. So
why not your body's natural enzymatic antioxidant defense system?
The facts are that reductionists pigs like you, don't even have the tools
required to evaluate complex systems. And, you certainly have no incentive
to even attempt to put yourself financially out of business. So, how can
you produce the ANSWER when you don't even know what the QUESTION is?
Any fool can be NEGATIVE. So please continue to make a fool of yourself in
public, Steve. And, let the truly innovative people make progress on their
own dime.
--
John Gohde,
Achieving good Nutrition is an Art, NOT a Science!
The nutrition of eating a healthy diet is the foundation of the biomedical
model of natural health. Weighing in at 16 webpages, Nutrition
(www.Food.NaturalHealthPerspective.com/) is now with more documentation and
sharper terminology than ever before.
Dave B
> "Nelson J. Navarro" <nnav...@adelphia.net> wrote in message
> news:fDvk8.1632$Zr3.6...@news1.news.adelphia.net...
>> > COMMENT:
>> >
>> > But that becomes an endless comment, because the combo of antioxidants
>> used
>> > today is never the one that will be in vogue tomorrow.
>>
>> Well sure it does, but that's because science is progressing.
>>
>> The computers manufactured five years from now will be better than the
>> one
> I
>> have now; cars will be more sophisticated;
>> anti-diabetic drugs will be more effective, etc.; why wouldn't the same
>> be true of newly discovered antioxidants?
>
>
> "Progressing" means progressing from something that works to something
> that works better, as with computers. Antioxidants basically don't "work"
> very well, if at all in people, and never have (show me the study that
> they lengthen life). The belief that they will one day is touching, but
> I'm afraid it remains to be proven.
But people have only been taking supplements for 40 years at most. It's a
whole new area. I'll keep in mind what you have to say regarding
antioxidants and lifespan. But I am most interested in the potential
ability of large doses to reduce the damage from acute insults on the body.
I would agree that in the garden of eden all one needs is diet but things
are a little different on 21st century earth.
You admit that antioxidant supplements are beneficial for heart disease yet
dismiss the idea that they might be helpful for anything else. And what
about diabetes? An extremely common condition largely characterized by high
oxidative stress. How about protection of DNA?
Still, your profession has come a long way. If you'd made some of your
statements on the benefits of antioxidants for heart disease 50 years ago
you would have been just as ridiculed and dismissed as the Shute brothers.
>
>> As evidence mounts that oxidative damage to mitochondria plays a
> significant
>> role in aging, and new compounds are discovered that protect mitochondria
>> much more effectively than "Vitamin E", for example, we will need to test
>> them before we say they won't work, no?
>
> COMMENT:
>
> Yes. But until then, you have only a theory. And not a very good one.
> You're made of more than just mitochondria.
>
> I've given you the counter-theory here before. Free radicals are the
> signals used by the body's inflammatory system, which is necessary for
> infection-fighting, normal healing, and for fighting some (not all) kinds
> of
> cancer. Free radicals (including deliberately produced ones like NO.)
> aren't just garbage to be expunged in every possible way you can think of,
> but rather instead are often important signals, not to be ignored. You
> can't just willy-nilly shotgun them, and the system which uses them, out
> of existence for long, without expecting to pay a price. Nature didn't
> give it all of that complicated radical-producing and radical-sensing
> machinery to you, for nothing.
Are you suggesting that large exogenous doses of antioxidants could
potentially reduce free radicals to such an extent that the body's natural
ability to use them for beneficial purposes becomes impaired? I have been
under the impression that while the body does indeed require free radicals
to be healthy, the problem is nearly always an excess of them.
> How long can you shotgun the entire free radical signal pathways in your
> body, and get away with it?
That's it - no more blueberries and spinach for me. I'm going on
unfortified rat chow till I die. :-)
Perhaps hours, if you're treating some really
> bad and inappropriate inflammation, such as reperfusion injury. Maybe
> days,
> if lucky. Not months or years, unless you'd like to live in a plastic
> bubble.
There is evidence to support this assertion? It goes both ways, you know.
If anybody comes up with something that protects mitochondia from
> free radicals they produce, if it is to be used for a life-time it's going
> to have to be remarkable for its *specificity*, NOT its generality.
> But I see that the dopey spirit of Pearson and Shaw is still alive and
> well on at least one newsgroup.
They seem to be doing pretty well judging by the recent issue of Life
Extension Magazine. And you too. :-)
Dave B.
CBI
"John 'Knows All'" <John 'Knows All'@hotmail.com> wrote in message
news:ZIAk8.12213$tP2.1...@bgtnsc05-news.ops.worldnet.att.net...
> Steve Harris <sbhar...@ix.netcom.com> wrote in message
> news:a6ugke$nfs$1...@slb7.atl.mindspring.net...
>
> > Antioxidants basically don't "work" very
> > well, if at all in people, and never have (show me the study that they
> > lengthen life).
>
> If antioxidants don't work, then why does your body have an antioxidant
> system?
>
If your body needs more antioxidants why doesn't it just make more? The
default assumption has always got to be that evolution has selected the most
advantageous traits. Mistakes don't get widely spread, only traits that
confer an advantage.
--
CBI, MD
Dave B
>
> "John 'Knows All'" <John 'Knows All'@hotmail.com> wrote in message
> news:ZIAk8.12213$tP2.1...@bgtnsc05-news.ops.worldnet.att.net...
>> Steve Harris <sbhar...@ix.netcom.com> wrote in message
>> news:a6ugke$nfs$1...@slb7.atl.mindspring.net...
>>
>> > Antioxidants basically don't "work" very
>> > well, if at all in people, and never have (show me the study that they
>> > lengthen life).
>>
>> If antioxidants don't work, then why does your body have an antioxidant
>> system?
>>
>
> If your body needs more antioxidants why doesn't it just make more?
Well, alot of people are idiots (myself included.) I think it's safe to
assume that their bodies are as well.
The
> default assumption has always got to be that evolution has selected the
> most advantageous traits. Mistakes don't get widely spread, only traits
> that confer an advantage.
That's why we can do things like smoke cigarettes for decades before we get
cancer. But evolution has not come even far enough. Now natural evolution
has reversed entirely. The only hope left is medical science or a profound
elevation in conciousness.
> --
> CBI, MD
watchman
Because .. it NEVER was 'supposed' to NEED more antioxidants than supplied
by our food.
But since man is a herbivore .. and the iron from the meat we eat
but aren't supposed to builds to toxic levels and rusts/oxidizes
destroying what antioxidants we DO have .. the body is INCAPABLE of
absorbing ENOUGH antioxidants from our foods.
Simple ..
Just like Pauling and Harmon have said .. we are rusting/oxidizing away.
Who loves ya.
Tom
--
Jesus was a Vegetarian! http://www.nucleus.com/watchman
Moses was a Mystic! http://www.nucleus.com/watchman/light.html
Chris Allen
> Peter H. Proctor wrote:
> > Another issue is that reducing antioxidants often ( usually ? )
> > also act as prooxidants. OTOH, PBN doesn't do this and can
> > extend maximum lifespan.
> Though not yet directly proven, all the benefits of PBN are likely
> to be even more true for its active and non-toxic moiety,
> N-tert-butyl-hydroxylamine (NtBHA).
But for this to be the case, Tom, NtBHA would have to share an
identical pharmacokinetic* profile with PBN (or, if it doesn't, the
difference would have then to be unimportant regarding PBN benefits).
One clue that it might well be the case that NtBHA _doesn't_ share
PBN's pharmacokinetic profile is the observed difference between PBN
and S-PBN (PBN's sulfo-derivative) neuroprotective effects in rat
brain:
"PBN and S-PBN treatment significantly reduced the loss of ipsilateral
hemispheric tissue whereas only S-PBN tended to reduce the cortical
lesion volume. PBN treatment caused a significant improvement in the
neurological score as compared to saline-treated animals, while S-PBN
alone attenuated the cognitive deficit. Our results suggest that
nitrone radical scavengers are neuroprotective when administered 30
min after FPI in rats. Differences in pharmacokinetics may account for
the observed individual neuroprotective profiles of the two nitrones."
-- J Neurotrauma 2001 Aug;18(8):821-32
PMID: 11526988
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11526988&dopt=Abstract
If the pharmacokinetic profile of NtBHA (as it compares to PBN's
pharmacokinetic profile) is currently unknown, would it be
recommendable (until it _is_ known) to supplement with all three
chemicals -- PBN, S-PBN and NtBHA?
--
* pharmacokinetics:
The movement of foreign substances, particularly drugs, throughout the
body of an animal. Processes that influence the pharmacokinetics of a
compound include uptake, distribution throughout the body tissues, the
length of time the compound remains in the body, and its rate of
clearance (e.g. by metabolism or excretion).
A Dictionary of Science, Oxford University Press (1999)
http://xrefer.com/entry.jsp?xrefid=491173&secid=.-
--
-Chris
Nelson J. Navarro
> "Nelson J. Navarro" <nnav...@adelphia.net> wrote in message
> news:fDvk8.1632$Zr3.6...@news1.news.adelphia.net...
> > > COMMENT:
> > >
> > > But that becomes an endless comment, because the combo of antioxidants
> > used
> > > today is never the one that will be in vogue tomorrow.
> >
> > Well sure it does, but that's because science is progressing.
> >
> > The computers manufactured five years from now will be better than the
one
> I
> > have now; cars will be more sophisticated;
> > anti-diabetic drugs will be more effective, etc.; why wouldn't the same
be
> > true of newly discovered antioxidants?
>
>
> "Progressing" means progressing from something that works to something
that
> works better, as with computers.
Indeed.
Antioxidants basically don't "work" very
> well, if at all in people, and never have (show me the study that they
> lengthen life). The belief that they will one day is touching, but I'm
> afraid it remains to be proven.
I've tried dozens of keys in my front door, and none of them opened the
door; obviously, keys don't work. LOL!
>
>
> > As evidence mounts that oxidative damage to mitochondria plays a
> significant
> > role in aging, and new compounds are discovered that protect
mitochondria
> > much more effectively than "Vitamin E", for example, we will need to
test
> > them before we say they won't work, no?
>
> COMMENT:
>
> Yes. But until then, you have only a theory. And not a very good one.
Best one I've heard so far. You got a better one? Better than, say, the
theory that aging "just happens".
You're
> made of more than just mitochondria.
LOL! And my computer is made of much more than just a microprocessor, but if
the microprocessor doesn't work, neither does the computer.
As I've said, "as evidence mounts that oxidative damage to mitochondria
plays a significant role in aging, and new compounds are discovered that
protect mitochondria much more effectively than "Vitamin E", for example, we
will need to test
them before we say they won't work, no?"
>
> I've given you the counter-theory here before. Free radicals are the
signals
> used by the body's inflammatory system, which is necessary for
> infection-fighting, normal healing, and for fighting some (not all) kinds
of
> cancer. Free radicals (including deliberately produced ones like NO.)
> aren't just garbage to be expunged in every possible way you can think of,
> but rather instead are often important signals, not to be ignored. You
can't
> just willy-nilly shotgun them, and the system which uses them, out of
> existence for long, without expecting to pay a price. Nature didn't give
it
> all of that complicated radical-producing and radical-sensing machinery to
> you, for nothing.
That's not a "counter-theory", that's your favorite straw man. LOL!
>
> How long can you shotgun the entire free radical signal pathways in your
> body, and get away with it? Perhaps hours, if you're treating some really
> bad and inappropriate inflammation, such as reperfusion injury. Maybe
days,
> if lucky. Not months or years, unless you'd like to live in a plastic
> bubble. If anybody comes up with something that protects mitochondia from
> free radicals they produce, if it is to be used for a life-time it's going
> to have to be remarkable for its *specificity*, NOT its generality.
>
> But I see that the dopey spirit of Pearson and Shaw is still alive and
well
> on at least one newsgroup.
If it weren't for that tired old platitude, you'd have nothing to say.
Ok, my car wouldn't work properly if it weren't for friction, I couldn't go
anywhere.
In fact, the whole world wouldn't "work" properly.
Accordingly, you can't just wipe out friction, nothing would work properly.
Yet friction is one of the primary factors driving the "aging" of my car.
Obvoiusly, the key to a long mechanical lifetime for important parts of my
car, is to reduce friction in places like bearings and cylinder walls.
Why would aging be expected to be fundamentally different?
Peter H. Proctor
>From: Dave B <wire...@pacbell.net>
>Subject: Re: Another Negative Antioxidant Life Span Study in Rodents
>Steve Harris wrote:
>> But I see that the dopey spirit of Pearson and Shaw is still alive and
>> well on at least one newsgroup.
>>
>> SBH
>Dr. Packer, one of the world's leading researchers on antioxidants,
>apparently feels differently. So do many other scientists who have looked
>at the same data you have. What up with dat?
If you poll most free radical researchers, they generally take
antioxidants. And yes, we all know they are messengers. See. e.g.,
www.redoxsignalling.com .
Dr P
Peter H. Proctor
>From: Dave B <wire...@pacbell.net>
>Subject: Re: Another Negative Antioxidant Life Span Study in Rodents
>Are you suggesting that large exogenous doses of antioxidants could
>potentially reduce free radicals to such an extent that the body's natural
>ability to use them for beneficial purposes becomes impaired? I have been
>under the impression that while the body does indeed require free radicals
>to be healthy, the problem is nearly always an excess of them.
Exactly. this system is under pretty strict control. One example
involves nitric oxide. At lower levels, it is a messenger. But large
amounts produced in the presence of superoxide make peroxinitrite, an
important part of the immune defense. Same is true of supreoxide itself.
Dr P
John 'the Man'
Once upon a time, our fellow CBI
rambled on about "Re: Another Negative Antioxidant Life Span Study
in Rodents."
Our champion being bored in sci.med.nutrition retorts, thusly ...
Did you become a MD by chance, or were you in control?
In Nature some live and some die by chance alone.
You didn't practice what you are preaching here. Why should I let
fate decide if I live or die?
--
John Gohde,
Achieving good Nutrition is an Art, NOT a Science!
My hidden agenda is to improve my personal health. Beware of anybody
who brags about eating a lousy diet or smoking.
www.Food.NaturalHealthPerspective.com/
Presenting great rules of thumb to eat by!
CBI
"John 'the Man'" <DeMan[28]@hotmail.com> wrote in message
news:9c969usosal80qt16...@4ax.com...
>
> Did you become a MD by chance, or were you in control?
>
Yes, both.
--
CBI, MD
CBI
"Dave B" <wire...@pacbell.net> wrote in message
news:k3Bk8.15728$f93.3327798365@newssvr14.news.prodigy.com...
I freely admit, and often point out, that man's social situation has placed
new demands and interests that are not met by evolutionary factors. That is
not the point. The point is that we must assume that man has evolved the
optimal way until it is shown to be otherwise. Sometimes it will be
otherwise, but the burden of proof is on those who wish to call mother
nature wrong.
--
CBI, MD
John 'the Man'
Once upon a time, our fellow CBI
rambled on about "Re: Another Negative Antioxidant Life Span Study
in Rodents."
Our champion being bored in sci.med.nutrition retorts, thusly ...
>not the point. The point is that we must assume that man has evolved the
>optimal way until it is shown to be otherwise. Sometimes it will be
>otherwise, but the burden of proof is on those who wish to call mother
>nature wrong.
WRONG!
The only thing that we can assume is that man has evolved the optimal
way long enough for him to reproduce.
The only thing that we can assume is that mother nature is only
interested in killing off those past the age of reproduction.
The borden of proof is a fools game.
--
John Gohde,
Achieving good Nutrition is an Art, NOT a Science!
Steve Harris
> > But I see that the dopey spirit of Pearson and Shaw is still alive and
> > well on at least one newsgroup.
>
> They seem to be doing pretty well judging by the recent issue of Life
> Extension Magazine. And you too. :-)
>
> Dave B.
Now, now. Taking resuscitation research money from the LEF (which I do)
doesn't mean I set their policies, or endorse each and every one of their
stands on supplementation (gee, if I did, you'd question my integrity about
THAT, would you not?). I do think LEF is in general a force for health and
not harm, so it's not like taking money from the tobacco industry. And yes,
when the LEF starts pushing PBN, NtBHA, and some of the wilder
non-biochemicals things you've heard about on this group, for the average
person, they'll be hearing from me.
Steve Harris
> If it weren't for that tired old platitude, you'd have nothing to say.
If you do a google search for my handle on the net, you'll find out
immediately how untrue THAT is <g>.
> Ok, my car wouldn't work properly if it weren't for friction, I couldn't
go
> anywhere.
> In fact, the whole world wouldn't "work" properly.
> Accordingly, you can't just wipe out friction, nothing would work
properly.
>
> Yet friction is one of the primary factors driving the "aging" of my car.
>
> Obvoiusly, the key to a long mechanical lifetime for important parts of my
> car, is to reduce friction in places like bearings and cylinder walls.
>
> Why would aging be expected to be fundamentally different?
COMMENT
Umm, because you're not a car? But let's be general: you've just postulated
a wear and tear model, but even if that's what we're seeing in biology, what
makes you think that free radicals are the major source of biological wear
and tear, not to mention the failure of cells to divide to fix it? Nevermind
that antioxidants aren't going to keep your teeth from wearing out--- what
makes you think that they'll keep any adult organ from wearing out? You're
built from all kinds of one-shot devices besides your teeth (alveoli,
glomeruli, neurons) that there's no mechanism for perfectly replacing any of
them as an adult, when you lose one for any reason. Even if you cut yourself
you're left with a scar. It doesn't matter how many antioxidants you take,
you're still left with a scar at some level. It's never perfect. You're not
a perfectly self-repairing device, and that's not because you don't take
enough vitamin E.
Let's take another example: the Hayflick limit. Non-transformed
non-germline cells have a limit on how many times they can divide. This
almost certainly isn't due to oxidative damage, because a dozen experiments
have tried to fix it by dumping antioxidants on cells in dishes, and that
simply hasn't ever worked. To imagine it will work some day with some
antioxidant we haven't found yet, is an article of faith. It's nice, but
it's not science.
The older you get, the less well your cells make protein, divide, repair
themselves and the ground substance between them, and so on. And many
structures you're made of (neurons, muscles cells) can't divide anyway. The
one thing we know about aging is that agelessness, wherever we've definitely
observed it, requires cell division. But guess what? You probably lost the
chance to be entirely subject to reparative cell division when you grew
yourself a brain and filled it with synapse-associated memories.
Now, why do all these age-associated "defects" happen to older cells
(failure to divide, failure to repair without division)? I frame no single
hypotheses. I suspect the reasons are manifold. If they were simple and
easily fixed, I suspect Mother Nature would have done that for some complex
animals (ie, those with brains). We have no good reason to think She ever
has. All candidates for ageless animals are in hyperborean wild places
where there's good reason for skepticism. Can you say Shangri La?
Is it better to have one unifying hypothesis which is unproven, and which
has evidence against it (the non-oxidative Hayflick limit), rather than not
having a unifying hypothesis? Yes, I think so. It's more honest to say you
don't know, when you don't know. You can think of me as as taking the
"strong agnostic" position on the cause(s) of aging. That means I don't
know, but I don't think you do, either.
Dave
Steve Harris wrote:
I'm new to this newsgroup, and quite honestly this is not my area of
expertise. However, it looks to me as though you have challenged the
readers to battle perhaps the most fundamental of human tendencies; that
is, the tendency to believe what 'we' *want* to believe (e.g.,
"faith"). I am admittedly disappointed to see that the vast majority of
responses to this thread are indeed deeply rooted in "faith," and are
devoid of any meaningful scientific dialogue. C'mon people, here is an
opportunity to challenge your *own* wisdom; be *scientific* and use it! :-)
Dave
--
The following is my e-mail address in hexadecimal form:
64616a406e657431706c75732e636f6d
To e-mail me, covert back to corresponding characters.
To the best of my knowledge the address harvesters have
not yet caught on to this method. :-)
Nelson J. Navarro
> "Nelson J. Navarro" <nnav...@adelphia.net> wrote in message
news:xjIk8.1889
> > If it weren't for that tired old platitude, you'd have nothing to say.
>
>
> If you do a google search for my handle on the net, you'll find out
> immediately how untrue THAT is <g>.
>
>
> > Ok, my car wouldn't work properly if it weren't for friction, I couldn't
> go
> > anywhere.
> > In fact, the whole world wouldn't "work" properly.
> > Accordingly, you can't just wipe out friction, nothing would work
> properly.
> >
> > Yet friction is one of the primary factors driving the "aging" of my
car.
> >
> > Obvoiusly, the key to a long mechanical lifetime for important parts of
my
> > car, is to reduce friction in places like bearings and cylinder walls.
> >
> > Why would aging be expected to be fundamentally different?
>
>
> COMMENT
>
> Umm, because you're not a car?
Sorry, I didn't mean to talk over your head.
I merely used an automobile analogy to try to get my point across; the point
being that I'm not advocating (as you seem to imply that I am) a
stoichiometric shotgun attack on free radicals, but rather, the delivery of
the proper agent to the proper location.
But let's be general: you've just postulated
> a wear and tear model, but even if that's what we're seeing in biology,
what
> makes you think that free radicals are the major source of biological wear
> and tear, not to mention the failure of cells to divide to fix it?
What I originally stated was, I believe "oxidative damage to mitochondria
plays a significant role in aging", I neither stated nor implied an
exclusive role, if that's what you're implying.
Nevermind
> that antioxidants aren't going to keep your teeth from wearing out--- what
> makes you think that they'll keep any adult organ from wearing out? You're
> built from all kinds of one-shot devices besides your teeth (alveoli,
> glomeruli, neurons) that there's no mechanism for perfectly replacing any
of
> them as an adult, when you lose one for any reason. Even if you cut
yourself
> you're left with a scar. It doesn't matter how many antioxidants you
take,
> you're still left with a scar at some level. It's never perfect. You're
not
> a perfectly self-repairing device, and that's not because you don't take
> enough vitamin E.
Obviously.
>
> Let's take another example: the Hayflick limit. Non-transformed
> non-germline cells have a limit on how many times they can divide. This
> almost certainly isn't due to oxidative damage, because a dozen
experiments
> have tried to fix it by dumping antioxidants on cells in dishes, and that
> simply hasn't ever worked. To imagine it will work some day with some
> antioxidant we haven't found yet, is an article of faith. It's nice, but
> it's not science.
You're actually claiming that oxidative stress plays no role in the
replicative senescence of cells? LOL!
>
> The older you get, the less well your cells make protein, divide, repair
> themselves and the ground substance between them, and so on. And many
> structures you're made of (neurons, muscles cells) can't divide anyway.
The
> one thing we know about aging is that agelessness, wherever we've
definitely
> observed it, requires cell division. But guess what? You probably lost
the
> chance to be entirely subject to reparative cell division when you grew
> yourself a brain and filled it with synapse-associated memories.
>
> Now, why do all these age-associated "defects" happen to older cells
> (failure to divide, failure to repair without division)? I frame no
single
> hypotheses. I suspect the reasons are manifold. If they were simple and
> easily fixed, I suspect Mother Nature would have done that for some
complex
> animals (ie, those with brains). We have no good reason to think She ever
> has. All candidates for ageless animals are in hyperborean wild places
> where there's good reason for skepticism. Can you say Shangri La?
>
> Is it better to have one unifying hypothesis which is unproven, and which
> has evidence against it (the non-oxidative Hayflick limit),
First, I don't agree with you that oxidative stress plays no role in
replicative senescence; second, I've neither stated nor implied a belief
that oxidative stress by itself fully explains aging.
rather than not
> having a unifying hypothesis? Yes, I think so. It's more honest to say
you
> don't know, when you don't know. You can think of me as as taking the
> "strong agnostic" position on the cause(s) of aging. That means I don't
> know, but I don't think you do, either.
>
I don't claim to know. I do have certain beliefs, however, and I think they
are defensible:
I believe oxidative damage plays a significant, but not necessarily
exclusive role in aging;
I believe we are close to having (if we don't already have) some
antioxidants which will be shown to directly modulate the rate of aging. (By
the way, I also believe that we are relatively close to having some drugs
that will be shown to modulate aging indirectly, possibly through some kind
of PPAR signalling);
I believe that just because vitamin E and strawberry extract and a dozen
other well known antioxidants do nothing to modulate aging doesn't mean that
other antioxidants won't.
Nelson J. Navarro
>
> "Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
> news:a70fcj$a9m$1...@slb7.atl.mindspring.net...
> > "Nelson J. Navarro" <nnav...@adelphia.net> wrote in message
> news:xjIk8.1889
>
they
> are defensible:
>
> I believe oxidative damage plays a significant, but not necessarily
> exclusive role in aging;
> I believe we are close to having (if we don't already have) some
> antioxidants which will be shown to directly modulate the rate of aging.
(By
> the way, I also believe that we are relatively close to having some drugs
> that will be shown to modulate aging indirectly, possibly through some
kind
> of PPAR signalling);
> I believe that just because vitamin E and strawberry extract and a dozen
> other well known antioxidants do nothing to modulate aging doesn't mean
that
> other antioxidants won't.
>
I forgot to add that I use the term "antioxidant" in a broad sense, meant to
include chelators, which would indirectly reduce oxidative stress by
removing ferrous iron, for example.
Steve Harris
> I merely used an automobile analogy to try to get my point across; the
point
> being that I'm not advocating (as you seem to imply that I am) a
> stoichiometric shotgun attack on free radicals, but rather, the delivery
of
> the proper agent to the proper location.
Okay, that's better, but I still don't like some of your candidates. Alpha
lipoic acid, which you mentioned, is a general suppressor of NO synthesis,
probably by affecting redox states in inflammatory cells. It's a two edged
sword-- it can restore NO responsiveness in systems which have been so
oxidized they've lost it, and it can suppress NO synthesis in immune cells
that are making it in response to infections. My point is that it's not just
something you dump on to try to stop or slow aging in the normal person.
That's not even a good thought experiment.
As for NtBHA, or the Murphy-mitochondria-targeted molecules, maybe they'll
be the magic bullets. Maybe not. We know too little about what they do in
biological systems to even guess at this point. For all I know NtBHA might
even generate NO. If it does, it might be great for epithelia, but perhaps
not something you want inside working mitochondria. Who knows?
> What I originally stated was, I believe "oxidative damage to mitochondria
> plays a significant role in aging", I neither stated nor implied an
> exclusive role, if that's what you're implying.
Okay, what's your evidence for a "significant role"?
> > Let's take another example: the Hayflick limit. Non-transformed
> > non-germline cells have a limit on how many times they can divide. This
> > almost certainly isn't due to oxidative damage, because a dozen
> experiments
> > have tried to fix it by dumping antioxidants on cells in dishes, and
that
> > simply hasn't ever worked. To imagine it will work some day with some
> > antioxidant we haven't found yet, is an article of faith. It's nice,
but
> > it's not science.
>
> You're actually claiming that oxidative stress plays no role in the
> replicative senescence of cells? LOL!
Okay, Bub, let's see your evidence. I want it interventional, not
"epidemiologic" (associational). You don't get to claim that cigarettes
cause lung cancer unless you can do a study showing that getting people to
quit cuts their lung cancer risk. You don't get to claim that LDL blood
cholesterol contributes to atherosclerosis unless you can prospectively
change cholesterol in animals or people and show that this has an impact on
the disease.
So, where are these experiments in which replicative senescence of cells has
been significantly altered or eradicated by changing oxidative stress?
> I don't claim to know. I do have certain beliefs, however, and I think
they
> are defensible:
> I believe oxidative damage plays a significant, but not necessarily
> exclusive role in aging;
Well, I don't.
> I believe we are close to having (if we don't already have) some
> antioxidants which will be shown to directly modulate the rate of aging.
Well, I don't.
> (By the way, I also believe that we are relatively close to having some
drugs
> that will be shown to modulate aging indirectly, possibly through some
kind
> of PPAR signaling);
You're talking to a guy who's been trying to get Dr. Spindler to do a
rosiglitazone feeding trial for years. But don't expect much. These great
anti-aging ideas tend to be disappointing.
> I believe that just because vitamin E and strawberry extract and a dozen
> other well known antioxidants do nothing to modulate aging doesn't mean
that
> other antioxidants won't.
No, but it's evidence against the idea. Science is nothing if not
induction. One of the definitions of madness is continuing to do something
again and again, expecting something other than the historical outcome each
time. You can always convince yourself that this time there's a crucial
difference, of course. Wisdom is in realizing it's time to quit and take
stock.
I've beat my head against his wall more than you have. You're enthusiastic,
probably young, evidently inexperienced. Fine. Discoveries are made by such
people. Occasionally. If you can convince somebody to give you grant money,
or you can scrape up enough yourself, have at it.
It's fine if you come here with your enthusiasms. But I'm going to provide
the tempering counterpoint.
Steve Harris
news:FC57E6DDB7145C76.3CBE664A...@lp.airnews.net...
COMMENT:
Well, they sure as hell don't take PBN or NtBHA. Or even alpha lipoic acid.
Packer probably does, but the way you tell the pioneer is that he's the guy
with the arrow in his back. Packer's asking for it, if he keeps at this.
What's up with the difference in how Dr. Packer and I see the world? There
are many possibilities. One of them is that I've gone farther down the
"cocktail trail" than he has, in some ways, and I've "seen the elephant," as
it were, that lurks at the end of it. Or, if you like, the tigers. I've
given large doses of vitamin E, melatonin, PBN, NOS inhibitors, COX
inhibitors, basically the anti-radical anti-inflammation works, to dogs in
resuscitation trials. This works great on the brain but occasionally I see a
dog get pneumonia, and some of them die from it, with complete lung
consolidation, in as little as 12-24 hours, despite heavy IV antibiotics.
And in a very odd way: no fever, no left-shifted neutrophils, no increased
heart rate, no shock (except at the hypoxic end). The last time I saw
anything like that as a physician was treating leukemic patients with no
neutrophils. These dogs have neutrophils, but they're just not working.
Lookie ma-- an immune system, but it does nothing. Hmm.
Dr. Packer works with rats, presumably kept away from infections. When they
do get infected, I doubt he does careful labs and vital signs in the little
critters. And if he does, he's not a physician, and the funny results don't
set off his warning bells. They do mine.
Dave B
> "Peter H. Proctor" <ppro...@neosoft.com> wrote in message
> news:FC57E6DDB7145C76.3CBE664A...@lp.airnews.net...
>> In article <%qAk8.8079$wB4.312...@newssvr21.news.prodigy.com> Dave B
> <wire...@pacbell.net> writes:
>> >From: Dave B <wire...@pacbell.net>
>> >Subject: Re: Another Negative Antioxidant Life Span Study in Rodents
>> >Date: Sat, 16 Mar 2002 05:08:11 GMT
>>
>> >Steve Harris wrote:
>>
>> >> But I see that the dopey spirit of Pearson and Shaw is still alive and
>> >> well on at least one newsgroup.
>> >>
>> >> SBH
>>
>> >Dr. Packer, one of the world's leading researchers on antioxidants,
>> >apparently feels differently. So do many other scientists who have
>> >looked at the same data you have. What up with dat?
>>
>> If you poll most free radical researchers, they generally take
>> antioxidants. And yes, we all know they are messengers. See. e.g.,
>> www.redoxsignalling.com .
>
>
> COMMENT:
>
> Well, they sure as hell don't take PBN or NtBHA. Or even alpha lipoic
> acid. Packer probably does, but the way you tell the pioneer is that he's
> the guy
> with the arrow in his back. Packer's asking for it, if he keeps at this.
He IS 70 years and still working full-time.
>
> What's up with the difference in how Dr. Packer and I see the world?
> There are many possibilities. One of them is that I've gone farther down
> the "cocktail trail" than he has, in some ways, and I've "seen the
> elephant," as it were, that lurks at the end of it. Or, if you like, the
> tigers. I've given large doses of vitamin E, melatonin, PBN, NOS
> inhibitors, COX inhibitors, basically the anti-radical anti-inflammation
> works, to dogs in resuscitation trials. This works great on the brain but
> occasionally I see a dog get pneumonia, and some of them die from it, with
> complete lung consolidation, in as little as 12-24 hours, despite heavy IV
> antibiotics. And in a very odd way: no fever, no left-shifted neutrophils,
> no increased heart rate, no shock (except at the hypoxic end). The last
> time I saw anything like that as a physician was treating leukemic
> patients with no neutrophils. These dogs have neutrophils, but they're
> just not working. Lookie ma-- an immune system, but it does nothing. Hmm.
Maybe those dogs crossed over to the other side and went toward the light
instead of back to your lab. If you want to move your research to humans
I'll volunteer. That'd be a trip. Ever seen Flatliners? ;-)
Seriously, how is taking antioxidant supplements any different from eating
alot of fruits/veggies with a high ORAC value? Besides the lack of all that
sugar. Were the doses used anywhere near comparable to that of the average
life-extender?
On a separate note: Isn't it likely that taking the right antioxidants
would help protect human DNA from radical-induced damage and subsequent
mutations?
> Dr. Packer works with rats, presumably kept away from infections. When
> they do get infected, I doubt he does careful labs and vital signs in the
> little critters. And if he does, he's not a physician, and the funny
> results don't set off his warning bells. They do mine.
I want to check into this further. Thanks for the info.
DB
Dave B
True. I want to believe.
DB
John Dye
wrote:
>Hi Steve and all,
>It certanly is a challenge for supplement users to explain why they
>expect great benefits from antioxidants when their distant cousins see
>very few. The full text of the above article references a few
>beneficial studies, but no real headliners. The N Y Academy of Science
>has now made its full text free on line and their format in which
>similar articles are grouped together in one volumn makes for some
>great browsing. For instance this article is in a volumn practicle
>interventions to slow the aging process. It is the best collection I
>have seen, and I expect to be reading it for the next week or month.
>Just paste Ann N Y Acad Sci in the medline search box, click on any
>article, Then the Academy icon, then archives, then 1998, then volumn
>854.
Thomas,
Thank you very much for this lead into the NY Academy of Science.
It is one of the most valuable links I have seen in a long while.
John
Chris
<FC57E6DDB7145C76.3CBE664A...@lp.airnews.net>,
ppro...@neosoft.com says...
Come down from alt.baldspot for a bit of peace and quiet eh?
Just curious, over the years you seem to have spoken sense steadily and
quietly; what do you take these days & why?
I am not just lazy but it has got to the point where: to remember
something new, I have to forget something old & I just can't see the
antioxidant/vitamin wood for the trees anymore.
(hair growing nicely btw.)
Pip pip
--
Chris Notton
}<////(*>
Dave B
> "Dave B" <wire...@pacbell.net> wrote in message news:4NAk8.15726
>> > But I see that the dopey spirit of Pearson and Shaw is still alive and
>> > well on at least one newsgroup.
>>
>> They seem to be doing pretty well judging by the recent issue of Life
>> Extension Magazine. And you too. :-)
>>
>> Dave B.
>
>
> Now, now. Taking resuscitation research money from the LEF (which I do)
> doesn't mean I set their policies, or endorse each and every one of their
> stands on supplementation (gee, if I did, you'd question my integrity
> about
> THAT, would you not?). I do think LEF is in general a force for health
> and
> not harm, so it's not like taking money from the tobacco industry. And
> yes, when the LEF starts pushing PBN, NtBHA, and some of the wilder
> non-biochemicals things you've heard about on this group, for the average
> person, they'll be hearing from me.
>
> SBH
Oh, I didn't mean it that way. I was honestly commenting on how
Durk and Sandy are doing very well in their court battles for health
freedom and, imo, look pretty good after all these years (don't know how
old they are, tho.) And that you also look and sound good in the issue
(although dropping a few pounds couldn't hurt.)
DB
John 'the Man'
Once upon a time, our fellow Dave
rambled on about "Re: Another Negative Antioxidant Life Span Study
in Rodents."
Our champion being bored in sci.med.nutrition retorts, thusly ...
>I am admittedly disappointed to see that the vast majority of
>responses to this thread are indeed deeply rooted in "faith," and are
>devoid of any meaningful scientific dialogue. C'mon people, here is an
>opportunity to challenge your *own* wisdom; be *scientific* and use it! :-)
Meaning what? Could it be that they don't agree with you?
Steve Harris
And that you also look and sound good in the issue
> (although dropping a few pounds couldn't hurt.)
>
> DB
Yeah. I've got at least 15 more to go. Never have a formal picture taken of
you early in January.
Steve Harris
> >> If you poll most free radical researchers, they generally take
> >> antioxidants. And yes, we all know they are messengers. See. e.g.,
> >> www.redoxsignalling.com .
> >
> >
> > COMMENT:
> >
> > Well, they sure as hell don't take PBN or NtBHA. Or even alpha lipoic
> > acid. Packer probably does, but the way you tell the pioneer is that
he's
> > the guy
> > with the arrow in his back. Packer's asking for it, if he keeps at
this.
>
> He IS 70 years and still working full-time.
Comment:
Well, fine that that's nothing special. He probably takes carnosine and
alpha lipoic acid, but not for 70 years. Whether he takes PBN or not, I have
no idea. I'm willing to wait. I have the feeling we'll see a lot of
infectious deaths in these life extenders, and a lot of comments of the sort
that "Gee, he looked great and would have lived to be 100, but for happening
unluckily to die of pneumonia (or whatever)." And let me know when Packer
has tested his cocktails on rodents with the flu or garden-variety
pneumococcal pneumonia.
> Maybe those dogs crossed over to the other side and went toward the light
> instead of back to your lab. If you want to move your research to humans
> I'll volunteer. That'd be a trip. Ever seen Flatliners? ;-)
Yes, and you don't want to volunteer, as humans that lose a lot of neurons
to post anoxic encephalopathy end up Democrats. It's horrible. Let them go
without oxygen for even longer, and they end up sounding like John Gohde.
And yes, the experiments are very much like in Flatliners, except the dogs
go as long as 15 minutes before being zapped back. They have a long rehab,
but eventually recover. We're eventually going to try for 20.
> Seriously, how is taking antioxidant supplements any different from eating
> alot of fruits/veggies with a high ORAC value? Besides the lack of all
that
> sugar.
We don't know how much of the blueberry polyphenols or whatever you absorb
when you eat them. Also, this is being done with some pretty artificial
radical-traps that are much stronger than anything you see in nature (I
don't know of any natural nitrones in food).
> Were the doses used anywhere near comparable to that of the average
> life-extender?
No, they were much larger than anything anybody's likely to be taking. But
who knows what Durk and Sandy are up to, now? And who knows what chemicals
people having daring, lately? It's a good bet that you body's adapted fairly
well to keep you from having any radical-traps you eat in food suppress your
"pro-oxidative" defenses to the point that your neutrophils are impotent
against bacteria. But when you start shoveling in things like PBN, all bets
are off.
> On a separate note: Isn't it likely that taking the right antioxidants
> would help protect human DNA from radical-induced damage and subsequent
> mutations?
Maybe. It's not impossible that chemicals great for your DNA might push you
over the line on bacteria-fighting. The people of the future might have
fairly short-acting antiaging pills which they all go though drills on how
to use, including stopping them immediately for fever or any sign of
infection. Sort of like the Malthusian Drill in _Brave New World_. The
future will be (I'm sure) a weird place, and who knows what people will do
there? (Did you think 10 years ago you'd have be using a cell phone like you
do?). I'm merely pointing out that powerful medicines generally take a lot
of thought and practice to use correctly. If there is a good anti-free
radical cocktail in the future, it's not likely that it's going to be the
sort of thing that you can just pop and forget every evening, as you do your
vitamin E. "Life extenders" have been spoiled there, as they would have been
using homeopathy. Coming up are drugs that won't be as benign as vitamins.
They will really free-radical reduction to the limit, and they'll have side
effects, as with steroids, that will be spectacular.
Nelson J. Navarro
> "Nelson J. Navarro" <nnav...@adelphia.net> wrote in message
> news:fjQk8.2330$Zr3.1...@news1.news.adelphia.net...
>
> > I merely used an automobile analogy to try to get my point across; the
> point
> > being that I'm not advocating (as you seem to imply that I am) a
> > stoichiometric shotgun attack on free radicals, but rather, the delivery
> of
> > the proper agent to the proper location.
>
> Okay, that's better, but I still don't like some of your candidates. Alpha
> lipoic acid, which you mentioned, is a general suppressor of NO synthesis,
> probably by affecting redox states in inflammatory cells. It's a two edged
> sword-- it can restore NO responsiveness in systems which have been so
> oxidized they've lost it, and it can suppress NO synthesis in immune cells
> that are making it in response to infections. My point is that it's not
just
> something you dump on to try to stop or slow aging in the normal person.
> That's not even a good thought experiment.
Well, lots of people here take ALA, some in rather high dosages, with no ill
effects, as far as I know.
>
> As for NtBHA, or the Murphy-mitochondria-targeted molecules, maybe they'll
> be the magic bullets. Maybe not. We know too little about what they do in
> biological systems to even guess at this point. For all I know NtBHA might
> even generate NO. If it does, it might be great for epithelia, but perhaps
> not something you want inside working mitochondria. Who knows?
It needs to be tested.
>
> > What I originally stated was, I believe "oxidative damage to
mitochondria
> > plays a significant role in aging", I neither stated nor implied an
> > exclusive role, if that's what you're implying.
>
> Okay, what's your evidence for a "significant role"?
I'll guess I'll reply to that in a separate post.
>
>
>
> > > Let's take another example: the Hayflick limit. Non-transformed
> > > non-germline cells have a limit on how many times they can divide.
This
> > > almost certainly isn't due to oxidative damage, because a dozen
> > experiments
> > > have tried to fix it by dumping antioxidants on cells in dishes, and
> that
> > > simply hasn't ever worked. To imagine it will work some day with some
> > > antioxidant we haven't found yet, is an article of faith. It's nice,
> but
> > > it's not science.
> >
> > You're actually claiming that oxidative stress plays no role in the
> > replicative senescence of cells? LOL!
>
> Okay, Bub, let's see your evidence. I want it interventional, not
> "epidemiologic" (associational). You don't get to claim that cigarettes
> cause lung cancer unless you can do a study showing that getting people to
> quit cuts their lung cancer risk. You don't get to claim that LDL blood
> cholesterol contributes to atherosclerosis unless you can prospectively
> change cholesterol in animals or people and show that this has an impact
on
> the disease.
>
> So, where are these experiments in which replicative senescence of cells
has
> been significantly altered or eradicated by changing oxidative stress?
Z Gerontol Geriatr 1999 Apr;32(2):69-75 Related Articles, Books, LinkOut
[Replicative senescence as a model of aging: the role of oxidative stress
and telomere shortening--an overview]
[Article in German]
Saretzki G, von Zglinicki T.
Institut fur Pathologie, Humboldt-Universitat zu Berlin.
Replicative senescence is characterized by the irreversible loss of division
potential of cultivated human and animal cells. Correlations between the
replicative potential in vitro and the age of the donor or the maximal
lifespan of the species suggest replicative senescence to be an appropriate
model for aging. Telomeres of human somatic cells shorten with each cell
division but are stabilized at constant length in tumors and immortal cells
by the enzyme telomerase. The assumption of a causal role of telomere
shortening for the limited lifespan of cells in vitro was borne out
recently. We could demonstrate oxidative stress as a main reason for
telomere shortening. Telomeres are sensors for oxidative damage in the
genome. Telomeres shorten during in vivo aging as well; however, there are
significant differences between individuals. Telomere erosion might play a
major role for the aging of the immune system. Our data suggest that
telomere shortening in vivo could reflect the cumulative amount of oxidative
damage to the organism. It might be useful as a biomarker of aging.
PMID: 10408009 [PubMed - indexed for MEDLINE]
Life Sci 1998;63(11):935-48 Related Articles, Books, LinkOut
Age-dependent telomere shortening is slowed down by enrichment of
intracellular vitamin C via suppression of oxidative stress.
Furumoto K, Inoue E, Nagao N, Hiyama E, Miwa N.
Department of Cell Biochemistry, Hiroshima Prefectural University School of
BioSciences, Shobara, Japan.
Telomeres in eukaryotic somatic cells are destined to the age-dependent
shortening, which has not been demonstrated to correlate to direct lesion of
telomeric DNA by reactive oxygen intermediates (ROI); still less explicable
is the inhibitory effect of ROI-scavenging on telomere shortening. Here, we
succeeded in artificial slowdown of age-dependent telomere shortening to
52-62% of the untreated control, in human vascular endothelial cells, by
addition of the oxidation-resistant type of ascorbic acid (Asc),
Asc-2-O-phosphate (Asc2P), which concurrently achieved both extension of
cellular life-span and prevention of cell size enlargement indicative of
cellular senescence. The results are attributable to a 3.9-fold more marked
enrichment of intracellular Asc (Asc(in)) by addition of Asc2P, subsequently
dephosphorylated before or during transmembrane influx, than by addition of
Asc itself, and also attributed to diminution of intracellular ROI to 53% of
the control level by Asc2P; telomerase activity was at a trace level and
underwent an age-dependent decline, which was significantly decelerated by
Asc2P. Thus, age-dependent telomere-shortening can be decelerated by
suppression of intracellular oxidative stress and/or by telomerase
retention, both of which are achieved by enriched Asc(in) but not by
extracellular Asc overwhelmingly more abundant than Asc(in).
PMID: 9747894
J Biol Chem 2000 Mar 10;275(10):6741-8 Related Articles, Books, LinkOut
N-t-butyl hydroxylamine, a hydrolysis product of alpha-phenyl-N-t-butyl
nitrone, is more potent in delaying senescence in human lung fibroblasts.
Atamna H, Paler-Martinez A, Ames BN.
Division of Biochemistry and Molecular Biology, Department of Molecular and
Cell Biology, University of California, Berkeley, California 94720-3202,
USA.
Alpha-phenyl-N-t-butyl nitrone (PBN), a spin trap, scavenges hydroxyl
radicals, protects tissues from oxidative injury, and delays senescence of
both normal human lung fibroblasts (IMR90) and senescence-accelerated mice.
N-t-butyl hydroxylamine and benzaldehyde are the breakdown products of PBN.
N-t-Butyl hydroxylamine delays senescence of IMR90 cells at concentrations
as low as 10 microM compared with 200 microM PBN to produce a similar
effect, suggesting that N-t-butyl hydroxylamine is the active form of PBN.
N-Benzyl hydroxylamine and N-methyl hydroxylamine compounds unrelated to PBN
were also effective in delaying senescence, suggesting the active functional
group is the N-hydroxylamine. All the N-hydroxylamines tested significantly
decreased the endogenous production of oxidants, as measured by the
oxidation of 2', 7'-dichlorodihydrofluorescin and the increase in the
GSH/GSSG ratio. The acceleration of senescence induced by hydrogen peroxide
is reversed by the N-hydroxylamines. DNA damage, as determined by the level
of apurinic/apyrimidinic sites, also decreased significantly following
treatment with N-hydroxylamines. The N-hydroxylamines appear to be effective
through mitochondria; they delay age-dependent changes in mitochondria as
measured by accumulation of rhodamine-123, they prevent reduction of
cytochrome C(FeIII) by superoxide radical, and they reverse an age-dependent
decay of mitochondrial aconitase, suggesting they react with the superoxide
radical.
PMID: 10702229 [PubMed - indexed for MEDLINE]
>
> > I don't claim to know. I do have certain beliefs, however, and I think
> they
> > are defensible:
> > I believe oxidative damage plays a significant, but not necessarily
> > exclusive role in aging;
>
> Well, I don't.
>
>
> > I believe we are close to having (if we don't already have) some
> > antioxidants which will be shown to directly modulate the rate of aging.
>
> Well, I don't.
I think you're too pessimistic.
>
>
> > (By the way, I also believe that we are relatively close to having some
> drugs
> > that will be shown to modulate aging indirectly, possibly through some
> kind
> > of PPAR signaling);
>
> You're talking to a guy who's been trying to get Dr. Spindler to do a
> rosiglitazone feeding trial for years. But don't expect much. These great
> anti-aging ideas tend to be disappointing.
Have you seen the following? Unlike the PPAR gamma agonist rosiglitazone,
which, if I recall correctly has little or no effect on HDLc, this stuff
boosted HDLc by 80%.
Proc Natl Acad Sci U S A 2001 Apr 24;98(9):5306-11 Related Articles, Books,
LinkOut
A selective peroxisome proliferator-activated receptor delta agonist
promotes reverse cholesterol transport.
Oliver WR Jr, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis
MC, Winegar DA, Sznaidman ML, Lambert MH, Xu HE, Sternbach DD, Kliewer SA,
Hansen BC, Willson TM.
Metabolic Diseases Drug Discovery and Nuclear Receptor Discovery Research,
GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
The peroxisome proliferator-activated receptors (PPARs) are dietary lipid
sensors that regulate fatty acid and carbohydrate metabolism. The
hypolipidemic effects of the fibrate drugs and the antidiabetic effects of
the glitazone drugs in humans are due to activation of the alpha (NR1C1) and
gamma (NR1C3) subtypes, respectively. By contrast, the therapeutic potential
of the delta (NR1C2) subtype is unknown, due in part to the lack of
selective ligands. We have used combinatorial chemistry and structure-based
drug design to develop a potent and subtype-selective PPARdelta agonist,
GW501516. In macrophages, fibroblasts, and intestinal cells, GW501516
increases expression of the reverse cholesterol transporter ATP-binding
cassette A1 and induces apolipoprotein A1-specific cholesterol efflux. When
dosed to insulin-resistant middle-aged obese rhesus monkeys, GW501516 causes
a dramatic dose-dependent rise in serum high density lipoprotein cholesterol
while lowering the levels of small-dense low density lipoprotein, fasting
triglycerides, and fasting insulin. Our results suggest that PPARdelta
agonists may be effective drugs to increase reverse cholesterol transport
and decrease cardiovascular disease associated with the metabolic syndrome
X.
PMID: 11309497
The paper is here:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=113
09497
Regards,
Nelson Navarro
Steve Harris
> Well, lots of people here take ALA, some in rather high dosages, with no
ill
> effects, as far as I know.
Yeah, but how would you? Unless it kills them like flies, you'd miss it.
COMMENT: Sorry, but we need to see the work which backs this claim (this guy
is reviewing his own work-- never the greatest objectivity when that
happens). So long as we're quoting reviews, see the one at the end of this
message. Cell lines with defects in antioxidant defences do not obviously
have accelerated senescence in culture (which is remarkable).
> Life Sci 1998;63(11):935-48 Related Articles, Books, LinkOut
>
> Age-dependent telomere shortening is slowed down by enrichment of
> intracellular vitamin C via suppression of oxidative stress.
>
> Furumoto K, Inoue E, Nagao N, Hiyama E, Miwa N.
>
> Department of Cell Biochemistry, Hiroshima Prefectural University School
of
> BioSciences, Shobara, Japan.
Different guys. And we'd like to see the actual delayed senescence, please.
This is the kind of thing I asked for. It still has problems:
1) The effect is modest, and of the same order as the negative effect of
culturing cells at room pO2 tensions, which are 10 times what they're used
to, and made for. This is known to shorten their replicative life (as Ames'
group showed, and others have shown before him), but fixing poisoning is not
the same as delaying aging. Ames knows this. He's forgotten to do the
obvious test, which is antioxidants at physiologic pO2 tensions.
2) Authors don't show this is a generic antioxidant effect. NtPBN is
presumably similar to plain vanilla hydroxylamine in being an .NO prodrug.
We know .NO is progrowth and anti-senescent in epithelia. How about
fibroblasts? Incidentally, I stood up in the audience at a geriatrics
conference in Washington more than 10 years ago and suggested that since PBN
is a prodrug for .NO, that may mediate some of its effects on circulation in
the brain. Richard Cutler was in the audience. The idea has received some
support since. PBN is a prodrug for NtBHA.
> Have you seen the following? Unlike the PPAR gamma agonist rosiglitazone,
> which, if I recall correctly has little or no effect on HDLc, this stuff
> boosted HDLc by 80%.
>
> Proc Natl Acad Sci U S A 2001 Apr 24;98(9):5306-11
> A selective peroxisome proliferator-activated receptor delta agonist
> promotes reverse cholesterol transport.
Interesting! We need something better than niacin. Hopefully this will
lead to a new class of drug treatment.
Here's the Ames paper on physiologic pO2 culture:
Proc Natl Acad Sci U S A 1995 May 9;92(10):4337-41
Oxidative DNA damage and senescence of human diploid fibroblast cells.
Chen Q, Fischer A, Reagan JD, Yan LJ, Ames BN.
Division of Biochemistry and Molecular Biology, University of California,
Berkeley 94720, USA.
Human diploid fibroblast cells cease growth in culture after a finite number
of population doublings. To address the cause of growth cessation in
senescent IMR-90 human fibroblast cells, we determined the level of
oxidative DNA damage by using 8-oxoguanine excised from DNA and
8-oxo-2'-deoxyguanosine in DNA as markers. Senescent cells excise from DNA
four times more 8-oxoguanine per day than do early-passage young cells. The
steady-state level of 8-oxo-2'-deoxyguanosine in DNA is approximately 35%
higher in senescent cells than in young cells. Measurement of protein
carbonyls shows that senescent cells did not appear to have elevated protein
oxidation. To reduce the level of oxidative damage, we cultured cells under
a more physiological O2 concentration (3%) and compared the replicative life
span to the cells cultured at the O2 concentration of air (20%). We found
that cells grown under 3% O2 achieved 50% more population doublings during
their lifetime. Such an extension of life span resulted from the delayed
onset of senescence and elevation of growth rate and saturation density of
cells at all passages. The spin-trapping agent alpha-phenyl-t-butyl nitrone
(PBN), which can act as an antioxidant, also effectively delayed senescence
and rejuvenated near senescent cells. The effect is dose-dependent and is
most pronounced for cells at the stage just before entry into senescence.
Our data support the hypothesis that oxidative DNA damage contributes to
replicative cessation in human diploid fibroblast cells.
PMID: 7753808 [PubMed - indexed for MEDLINE]
----------------------------------------------------------------------------
----
Here's the mostly negative review on cell culture, senescence, and
oxidation.
Mutat Res 1991 Mar-Nov;256(2-6):177-89
Oxidants and antioxidants in proliferative senescence.
Poot M.
Department of Human Genetics, University of Wurzburg, Germany.
In terms of the amount of experimental research it has generated the free
radical theory of ageing is one of the most popular hypotheses to explain
this ubiquitous phenomenon. From the theory two postulates were derived:
either cellular defence mechanisms against free radical-dependent oxidants
deteriorate during ageing of cells, or essential, unrepairable damages are
imparted to the cell by oxidants regardless of the activity of antioxidant
defence systems. The many reports dealing with a putative breakdown in
antioxidant defence systems failed to positively support this postulate.
However, a minor depletion in cellular glutathione by exposure to a model
lipophilic peroxide led to a significant decrement in DNA and protein
synthesis. In other words, the glutathione redox cycle is intrinsically
fallible with respect to defending the cellular DNA replication system
against this model lipophilic peroxide. Interestingly, after ageing in
culture cells a partial uncoupling of the NADPH-producing and -consuming
systems tends to take place. Experiments involving the addition of
antioxidants to the culture medium have failed to significantly extend the
lifespan of cultured diploid somatic cells. The level of antioxidants
appears to be a modulator rather than a primary determinant of cellular
ageing in culture. Several lines of evidence suggest that DNA damages
accumulate during ageing of the organism, but no oxidant-related DNA damage
has been pinpointed in the cultured cell system. Human mutants with defects
in antioxidant enzymes have not shown conclusive signs of accelerated
ageing. Cells from patients with Werner's syndrome (progeria of the adult),
on the other hand, do not suffer from a defect in their antioxidant defence
system, nor do they accumulate more than normal amounts of autofluorescent
products resulting from lipid peroxidation. The recent finding that Werner's
syndrome constitutes a mutator phenotype may prompt the comparison of
oxidant- and ageing-related mutation spectra in order to investigate a
mutational theory of ageing as a new derivative from the free radical
hypothesis.
PMID: 1722009 [PubMed - indexed for MEDLINE]
mark doran
> Unless it kills them like flies, you'd miss it.
>
Y'know, I've always found that a strange expression. Everywhere you go,
there's flies. Try and kill them, and you can't easily. Manage to kill them,
and soon there's more flies....
Funny we should have such an expression about some of the most successful
species ever!
Fascinating discussion though, gentlemen. I'm learning a lot.
M.
Nelson J. Navarro
> "Nelson J. Navarro" <nnav...@adelphia.net> wrote in message
> news:%m2l8.3636$Zr3.1...@news1.news.adelphia.net...
<snip>
Well, the results of this study were confirmed and extended in a subsequent
study, in which a NO prodrug effect was considered, controlled for, and
ruled out.
FASEB J 2001 Oct;15(12):2196-204 Related Articles, Books, LinkOut
N-t-Butyl hydroxylamine is an antioxidant that reverses age-related changes
in mitochondria in vivo and in vitro.
Atamna H, Robinson C, Ingersoll R, Elliott H, Ames BN.
Department of Molecular and Cell Biology, University of California,
Berkeley/CHORI, Oakland, California 94609, USA.
N-t-butyl hydroxylamine (NtBHA) delays senescence-dependent changes in human
lung fibroblasts (IMR90) (Atamna et al., J. Biol. Chem. 275, 6741-6748). The
current study examines the effect of NtBHA on mitochondria in old and young
rats and human primary fibroblasts (IMR90). In NtBHA-treated rats, the
age-dependent decline in food consumption and ambulatory activity was
reversed without affecting body weight. The respiratory control ratio of
mitochondria from liver of old rats improved after feeding NtBHA. These
findings suggest that NtBHA improved mitochondrial function in vivo. The
age-dependent increase in proteins with thiol-mixed disulfides was
significantly lower in old rats treated with NtBHA. NtBHA was effective only
in old rats; no significant effect was observed in young rats. In IMR90
cells, NtBHA delayed senescence-associated changes in mitochondria and
cellular senescence induced by maintaining the cells under suboptimal levels
of growth factors. Proteasomal activity was also higher in cells treated
with NtBHA than in untreated cells. NtBHA accumulates in cells 10- to
15-fold the extracellular concentration and is maintained by mitochondrial
NADH. NtBHA is an antioxidant that is recycled by mitochondrial electron
transport chain and prevents radical-induced toxicity to mitochondria.
PMID: 11641246 [PubMed - indexed for MEDLINE]
Regards,
Nelson Navarro
Matti Narkia
<a70nk7$7mi$1...@slb6.atl.mindspring.net> "Steve Harris"
<sbha...@ix.RETICULATEDOBJECTcom.com> wrote:
>What's up with the difference in how Dr. Packer and I see the world? There
>are many possibilities. One of them is that I've gone farther down the
>"cocktail trail" than he has, in some ways, and I've "seen the elephant," as
>it were, that lurks at the end of it. Or, if you like, the tigers. I've
>given large doses of vitamin E, melatonin, PBN, NOS inhibitors, COX
>inhibitors, basically the anti-radical anti-inflammation works, to dogs in
>resuscitation trials. This works great on the brain but occasionally I see a
>dog get pneumonia, and some of them die from it, with complete lung
>consolidation, in as little as 12-24 hours, despite heavy IV antibiotics.
>And in a very odd way: no fever, no left-shifted neutrophils, no increased
>heart rate, no shock (except at the hypoxic end). The last time I saw
>anything like that as a physician was treating leukemic patients with no
>neutrophils. These dogs have neutrophils, but they're just not working.
>Lookie ma-- an immune system, but it does nothing. Hmm.
>
A study by Meydani et al. in 1997 found that vitamin E supplementation
improved T-cell mediated immune response in elderly (over 65) people.
Three different daily doses were tried: 60, 200 and 800 mg. All the
doses improved immune response, but interestingly 200 mg dose was most
effective in this. Below the abstract:
Meydani SN, Meydani M, Blumberg JB, Leka LS, Siber G, Loszewski R,
Thompson C, Pedrosa MC, Diamond RD, Stollar BD.
Vitamin E supplementation and in vivo immune response in healthy elderly
subjects. A randomized controlled trial.
JAMA. 1997 May 7;277(17):1380-6.
PMID: 9134944 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9134944&dopt=Abstract
OBJECTIVE: To determine whether long-term supplementation with
vitamin E enhances in vivo, clinically relevant measures of cell-
mediated immunity in healthy elderly subjects. DESIGN: Randomized,
double-blind, placebo-controlled intervention study. SETTING AND
PARTICIPANTS: A total of 88 free-living, healthy subjects at least
65 years of age. INTERVENTION: Subjects were randomly assigned to
a placebo group or to groups consuming 60, 200, or 800 mg/d of
vitamin E for 235 days. MAIN OUTCOME MEASURES: Delayed-type
hypersensitivity skin response (DTH); antibody response to
hepatitis B, tetanus and diphtheria, and pneumococcal vaccines;
and autoantibodies to DNA and thyroglobulin were assessed before
and after supplementation. RESULTS: Supplementation with vitamin E
for 4 months improved certain clinically relevant indexes of cell-
mediated immunity in healthy elderly. Subjects consuming 200 mg/d
of vitamin E had a 65% increase in DTH and a 6-fold increase in
antibody titer to hepatitis B compared with placebo (17% and 3-
fold, respectively), 60-mg/d (41% and 3-fold, respectively), and
800-mg/d (49% and 2.5-fold, respectively) groups. The 200-mg/d
group also had a significant increase in antibody titer to tetanus
vaccine. Subjects in the upper tertile of serum alpha-tocopherol
(vitamin E) concentration (>48.4 micromol/L [2.08 mg/dL]) after
supplementation had higher antibody response to hepatitis B and
DTH. Vitamin E supplementation had no effect on antibody titer to
diphtheria and did not affect immunoglobulin levels or levels of T
and B cells. No significant effect of vitamin E supplementation on
autoantibody levels was observed. CONCLUSIONS: Our results
indicate that a level of vitamin E greater than currently
recommended enhances certain clinically relevant in vivo indexes
of T-cell-mediated function in healthy elderly persons. No adverse
effects were observed with vitamin E supplementation."
-Matti Narkia
Dave
Steve Harris wrote:
> "Nelson J. Navarro" <nnav...@adelphia.net> wrote in message
> news:fDvk8.1632$Zr3.6...@news1.news.adelphia.net...
>
>>>COMMENT:
>>>
>>>But that becomes an endless comment, because the combo of antioxidants
>>>
>>used
>>
>>>today is never the one that will be in vogue tomorrow.
>>>
>>Well sure it does, but that's because science is progressing.
>>
>>The computers manufactured five years from now will be better than the one
>>
> I
>
>>have now; cars will be more sophisticated;
>>anti-diabetic drugs will be more effective, etc.; why wouldn't the same be
>>true of newly discovered antioxidants?
>>
>
>
> "Progressing" means progressing from something that works to something that
> works better, as with computers. Antioxidants basically don't "work" very
> well, if at all in people, and never have (show me the study that they
> lengthen life). The belief that they will one day is touching, but I'm
> afraid it remains to be proven.
>
>
>
>>As evidence mounts that oxidative damage to mitochondria plays a
>>
> significant
>
>>role in aging, and new compounds are discovered that protect mitochondria
>>much more effectively than "Vitamin E", for example, we will need to test
>>them before we say they won't work, no?
>>
>
> COMMENT:
>
> Yes. But until then, you have only a theory. And not a very good one. You're
> made of more than just mitochondria.
>
> I've given you the counter-theory here before. Free radicals are the signals
> used by the body's inflammatory system, which is necessary for
> infection-fighting, normal healing, and for fighting some (not all) kinds of
> cancer. Free radicals (including deliberately produced ones like NO.)
Are there any endogenous free radicals that actually behave as
*anti-oxidants*? I ask because when you mentioned NO, I immediately
began thinking of TEMPO, a "stable free radical" and spin label. Of
course, TEMPO is synthetically produced, but that may me wonder about
the possibility of endogenous radicals behaving as anti-oxidants.
Dave
> aren't just garbage to be expunged in every possible way you can think of,
> but rather instead are often important signals, not to be ignored. You can't
> just willy-nilly shotgun them, and the system which uses them, out of
> existence for long, without expecting to pay a price. Nature didn't give it
> all of that complicated radical-producing and radical-sensing machinery to
> you, for nothing.
>
> How long can you shotgun the entire free radical signal pathways in your
> body, and get away with it? Perhaps hours, if you're treating some really
> bad and inappropriate inflammation, such as reperfusion injury. Maybe days,
> if lucky. Not months or years, unless you'd like to live in a plastic
> bubble. If anybody comes up with something that protects mitochondia from
> free radicals they produce, if it is to be used for a life-time it's going
> to have to be remarkable for its *specificity*, NOT its generality.
>
> But I see that the dopey spirit of Pearson and Shaw is still alive and well
> on at least one newsgroup.
>
> SBH
>
> --
> I welcome Email from strangers with the minimal cleverness to fix my address
> (it's an open-book test). I strongly recommend recipients of unsolicited
> bulk Email ad spam use "http://combat.uxn.com" to get the true corporate
> name of the last ISP address on the viewsource header, then forward message
> & headers to "abuse@[offendingISP]."
>
>
>
Peter H. Proctor
>From: Dave <da...@nospam.com>
>Subject: Re: Another Negative Antioxidant Life Span Study in Rodents
>Date: Mon, 18 Mar 2002 23:37:48 -0800
>Are there any endogenous free radicals that actually behave as
>*anti-oxidants*? I ask because when you mentioned NO, I immediately
>began thinking of TEMPO, a "stable free radical" and spin label. Of
>course, TEMPO is synthetically produced, but that may me wonder about
>the possibility of endogenous radicals behaving as anti-oxidants.
Absolutely correct.... The most prevalent stable free radical in vivo
is the black pigment melanain, which is present in certain brain neuronal
cell bodies in humans, as well as the skin. Other animals have it other
places ( e.g., in liver ). There is also NO itself. BTW, I pointed out
the similarity between NO, TEMPO, etc. in a paper obout 13 years ago.
It is posted at http://www.drproctor.com/Archd.htm
Dr P
Steve Harris
>Are there any endogenous free radicals that actually behave as
>*anti-oxidants*? I ask because when you mentioned NO, I immediately
>began thinking of TEMPO, a "stable free radical" and spin label. Of
>course, TEMPO is synthetically produced, but that may me wonder about
>the possibility of endogenous radicals behaving as anti-oxidants.
>
>Dave
Now you're thinking. Dr. Proctor has mentioned melanin, which is not only
in skin, but probably in the substantia nigra in the brain in part to
suppress free-radical production there which is a side effect of dopamine
metabolism (and without which, the radicals may destroy things and you get
Parkinson's disease).
Nitric oxide (.NO) itself might act as a radical-adduct trap in places where
there's no .O2- (superoxide), which might be a lot of places in your body.
The .NO does indeed trap the radical superoxide, but the resulting
non-radical peroxynitrite (OONO-) is a powerful oxidant, and even nastier
than if it was a free radical.
--
I welcome email from any being clever enough to fix my address. It's open
book. A prize to the first spambot that passes my Turing test.
Chuck
> "Dave B" <wire...@pacbell.net> wrote in message news:4NAk8.15726
> > > But I see that the dopey spirit of Pearson and Shaw is still alive and
> > > well on at least one newsgroup.
> >
> > They seem to be doing pretty well judging by the recent issue of Life
> > Extension Magazine. And you too. :-)
> >
> > Dave B.
>
>
> Now, now. Taking resuscitation research money from the LEF (which I do)
> doesn't mean I set their policies, or endorse each and every one of their
> stands on supplementation (gee, if I did, you'd question my integrity about
> THAT, would you not?). I do think LEF is in general a force for health and
> not harm, so it's not like taking money from the tobacco industry. And yes,
> when the LEF starts pushing PBN, NtBHA, and some of the wilder
> non-biochemicals things you've heard about on this group, for the average
> person, they'll be hearing from me.
>
> SBH
What are your thoughts on using ALT-711 as a drug to help reverse AGE's?
Steve Harris
I think it needs a lot more animal and human testing first. Why, do you
have some? Where'd you get it?
Dave B
>>What are your thoughts on using ALT-711 as a drug to help reverse AGE's?
>
>
> I think it needs a lot more animal and human testing first. Why, do you
> have some? Where'd you get it?
Corner of Adams and Crenshaw. Dude named Leroy will hook you up. But be
careful down there Steve.
Tom Matthews
> Tom Matthews <t...@morelife.org> wrote in message news:<3C91A2E4...@morelife.org>...
>
>>Peter H. Proctor wrote:
>>
>>> Another issue is that reducing antioxidants often ( usually ? )
>>>also act as prooxidants. OTOH, PBN doesn't do this and can
>>>extend maximum lifespan.
>>>
>>Though not yet directly proven, all the benefits of PBN are likely
>>to be even more true for its active and non-toxic moiety,
>>N-tert-butyl-hydroxylamine (NtBHA).
>>
>
> But for this to be the case, Tom, NtBHA would have to share an
> identical pharmacokinetic* profile with PBN (or, if it doesn't, the
> difference would have then to be unimportant regarding PBN benefits).
OR PBN might have some harmful effects which outweigh any "better"
pharmacokinetic profile.
It would be exceedingly strange if these two different chemicals had an
identical pharmacokinetic profile, so that was not even a consideration
in my reasoning.
> One clue that it might well be the case that NtBHA _doesn't_ share
> PBN's pharmacokinetic profile is the observed difference between PBN
> and S-PBN (PBN's sulfo-derivative) neuroprotective effects in rat
> brain:
>
> "PBN and S-PBN treatment significantly reduced the loss of ipsilateral
> hemispheric tissue whereas only S-PBN tended to reduce the cortical
> lesion volume. PBN treatment caused a significant improvement in the
> neurological score as compared to saline-treated animals, while S-PBN
> alone attenuated the cognitive deficit. Our results suggest that
> nitrone radical scavengers are neuroprotective when administered 30
> min after FPI in rats. Differences in pharmacokinetics may account for
> the observed individual neuroprotective profiles of the two nitrones."
> -- J Neurotrauma 2001 Aug;18(8):821-32
> PMID: 11526988
> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11526988&dopt=Abstract
>
> If the pharmacokinetic profile of NtBHA (as it compares to PBN's
> pharmacokinetic profile) is currently unknown, would it be
> recommendable (until it _is_ known) to supplement with all three
> chemicals -- PBN, S-PBN and NtBHA?
I don't think so. I don't even know of the availability of S-PBN and I
have decided against using PBN instead of (or as well as) NtBHA because
of its known toxic benzaldehyde moiety. For more details see:
http://www.morelife.org/lifespan/reaching/researchems/NtBHA.html
--Tom Matthews
MoreLife for us all - http://morelife.org
Reality based tools for More Life in quantity & quality
Chuck
I have a little but I can't say where it came from.
Dave
Peter H. Proctor wrote:
Interestingly, I recently came across a study which suggested that the
potential benefits of L-deprenyl against Parkinson's Disease and [maybe]
Alzheimer's Disease may be mediated by its effect on NO production,
rather than the inhibition of MAO-B.
------------------------------------------------------------
L-deprenyl: nitric oxide production and dilation of cerebral blood
vessels by Thomas T, McLendon C, Thomas G
Woodlands Medical and Research Center, Oldsmar, FL 45677, USA.
Neuroreport 1998 Aug 3; 9(11):2595-600
The monoamine oxidase-B inhibitor L-deprenyl (Selegiline) is effective
in treating Parkinson's disease and possibly Alzheimer's disease. The
neuroprotective property of L-deprenyl may be unrelated to the
inhibition of monoamine oxidase-B. Since nitric oxide (NO) modulates
activities including cerebral blood flow and memory, we examined the
effect of L-deprenyl on NO. L-Deprenyl induced rapid increases in NO
production in brain tissue and cerebral vessels. Vasodilation was
produced by endothelial NO-dependent as well as NO-independent
mechanisms in cerebral vessels. The drug also protected the vascular
endothelium from the toxic effects of amyloid-beta peptide. These novel
actions of selegiline may protect neurons from ischemic or oxidative
damage and suggest new therapeutic applications for L-deprenyl in
vascular and neurodegenerative diseases.
> It is posted at http://www.drproctor.com/Archd.htm
>
> Dr P
>
Peter H. Proctor
>From: Dave <da...@nospam.com>
>Subject: Re: Another Negative Antioxidant Life Span Study in Rodents
>Interestingly, I recently came across a study which suggested that the
>potential benefits of L-deprenyl against Parkinson's Disease and [maybe]
>Alzheimer's Disease may be mediated by its effect on NO production,
>rather than the inhibition of MAO-B.
sometimes it is hard to separate out vascular dementia from alzheimers, and
vice versa. Each is though to contribute to the other.
Dr PO
Peter H Proctor
<sbha...@ix.RETICULATEDOBJECTcom.com> wrote:
>But now here you say that hydroxylamines
>
>C-N-OH
> C
>
>can lose a proton to superoxide, regenerating the nitoxyl C2- N-O' But
>you then call that a "spin trap".
Oops... I meant "spin label". Come fro flying thru to fast...
The hydroxylamines form the connection between the nitrone
spin traps and the Nitroxide spin labels. E.g., TEMPO nitroxide
radical readily gets reduced in vivo to form tempamine. ( which is
analogous to NtBHA ). This then reacts with superoxide to form TEMPO,
which is an SOD-mimetic. So the wheel goes round and round.
Nitroxides, being radicals, can form
>spin-adducts with things like superoxide O2'- and in that sense "trap" the
>radicals.
There is no better trap for free radicals than another free radical
and/or forming a stable radical ( as with the nitrone spin traps ).
Not only is the reaction fast, but eith one terminates free radical
chain reactions. Further, unl;ike reducing antioxidants, nitrones
and nitroxide don't seem to act much as proxidants.
> And TEMPO has been used as a cerebral resuscitation drug, as has
>PBN, so the general sponging of radicals is probably similar with these as
>it is in NtBHA.
The Pharmacological properties of nitrones,
hydroxyulamines, and the coreesponding nitroxides are rather similar
because the all scarf up on the same radicals, if by slightly
different mechanisms. Furhter, one form converts readily to
another. So this NtBHA stuff is not too surprising.
But "spin trap" (not a radical) and "spin label" (a radical)
>are used quite differently and not interchangably in the literature, as you
>well know (I see your many patents on these things).
Yes, I do know the difference. sometimes my fingers don't though
<G>...
Dr P