alpha lipoic acid eliminates wrinkles?
R&M
mbansch314
I doubt if lipoic acid is going to eliminate skin wrinkles. Omega-3 fatty
acids may work though.
Steve Harris
> wife wants to buy this stuff to look younger...any comments??/
Is she using Retin-A already??
--
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
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R&M
"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
news:a4sk4h$51g$1...@slb1.atl.mindspring.net...
Steve Harris
> no to retin a but she uses alpha hydroxy creams...
Well then tell her use the Retin-A instead of the lipoic acid, and get
something for the money that actually has been proven to work.
SBH
diana thorley
On Mon, 18 Feb 2002 19:58:16 -0800, "R&M" <tan...@ixpres.com> wrote:
>wife wants to buy this stuff to look younger...any comments??/
I thought they were all using Botox injections to eliminate wrinkles?.
Also, on the radio and TV today there have been reports of of a study
in the USA which proved that a combination of L-carnitine and lipoic
acid reversed the ageing process. The research company has patented
the combination the formula. Here in the UK these two products will
be missing from the shelves of the Health Food Stores.
DawnoftheForest
>From: "R&M" tan...@ixpres.com
>Date: 2/18/02 10:58 PM Eastern Standard Time
>Message-id: <3c71c...@news.vic.com>
>
>wife wants to buy this stuff to look younger...any comments??/
Though it has merits, alpha lipoic acid will do nothing for wrinkles. It will
relieve your wallet of some weight though.
If wrinkles concern you, don't be stick thin, stay out of the sun and away
from smoking and alcohol.
Exercise, and don't eat refined
sugar or trans fats.
That plan will do more for your skin than any pill ever did :-) Dawn
Steve Harris
news:3c728faf...@news.CIS.DFN.DE...
> Also, on the radio and TV today there have been reports of of a study
> in the USA which proved that a combination of L-carnitine and lipoic
> acid reversed the ageing process.
COMMENT:
They proved no such thing. For all we know, these mice may die at the same
age, but leave good-looking corpses. I once did a similar study with CoQ10,
which was very confusing. Aging is fundamental and is not going to be
greatly changed by two little nutrients (both of which your body can already
make). If you could slow aging this easily, why doesn't your body do it?
Evolution has no reason to want you to age more rapidly when you could be
(at a small synthetic cost) age more slowly.
Whatever the metabolic cost of aging even at a significantly slower rate (as
we see in bats and birds) it must be quite large. Big repairs are being done
in flying critters, and that burns a lot of energy. More than humans have
historically been able to pay on the kind of diet we have historically
gotten, methinks. I hardly think ALC and lipoic acid are going to be The
Answer.
>The research company has patented
> the combination the formula.
Oh, well, THAT increases my confidence.
mark doran
> "diana thorley" <dith...@aol.com> wrote in message
> news:3c728faf...@news.CIS.DFN.DE...
>
> > Also, on the radio and TV today there have been reports of of a study
> > in the USA which proved that a combination of L-carnitine and lipoic
> > acid reversed the ageing process.
>
> COMMENT:
> They proved no such thing. For all we know, these mice may die at the same
> age, but leave good-looking corpses.
Hmm. All the reports I've read so far talk about the experiment having used
elderly rats which perked up noticeably. If there was any increase in
maximum lifespan, it might have been too small to show up clearly: we'd have
to see figures for rats which began the treatment while *young*. We'll
probably get those results in a couple of years (how long do rats usually
live...?)
> I once did a similar study with CoQ10,
> which was very confusing.
Ooo! Do tell! What happened?
Regards,
M.
Jim Jozwiak
in rats?
Thanks,
Jim Jozwiak
Steve Harris
news:3c72e33b$0$233$cc9e...@news.dial.pipex.com...
> > I once did a similar study with CoQ10,
> > which was very confusing.
>
> Ooo! Do tell! What happened?
>
> Regards,
Half the mice got CoQ10 at 0.1% of dry diet for their entire lives, after
weaning. That's a LOT. (About like 7-10 GRAMS a day for people).
I didn't see as much of the "nursing home" appearance of old C57Bl0/CH3
hybrid mice, which results from hip arthritis (the back legs drag some) and
possibly spinal stenosis (since the mice quit grooming their hind quarters
and rears, which makes me think they can't feel them as well). The CoQ10
mice weren't as gray. They ran around and seemed to have lots more energy at
33 months (which is getting fairly old for a mouse-- it's about mean life
span in the long lived hybrids).
But they died nearly on schedule (only the mean life span increased, so the
curve was squared a bit). Three out of four of the last mice alive in the
CoQ10 group, who I expected to break my max life span record for 10%
restriction (which was about 43 months) died instead of lymphoma. A common
disease of mice. Which in this case had merely been shifted to an older
age. They left good-looking corpses. But for about a year there, I thought
I was going to be famous.
Repetition of this experiment is needed. Spindler et al have tried with a
lower dose of CoQ10 and got nothing, which makes me wonder if I wasn't
seeing some statistical fluke in a 35 vs 35 animal control trial. I'm about
to run another small trial in mice from my small colony, which already will
start out old (32 months). I'll pre-stratify them by weight and appearance,
then randomize them to 1 ppt CoQ10 or not. We'll see if I get similar
effects.
Steve Harris
news:a4uo4f$57l$1...@zook.lafn.org...
I'll tell you the biggest difference: rats have a lot MORE of them per cell.
If your metabolism is going to run 5 times as fast, you have to have 5 times
the number of powerhouses.
Martin Banschbach
Good question Jim.
Mitochondria are pretty well conserved among different animal
species. They all came from a bacterial infection of a unicellular
organisim and the bacteria was walled off (outer mitochondrial
membrane)
and the extra energy coming from the captured bacteria allowed the
unicellular organism to get enough energy to become a multicellular
organism.
All of us here owe our existence to a lowly bacterium.
The mitocohndria has DNA that codes for some of the enzymes needed to
produce ATP. Mitochondria wear out all of the time because of all of
the oxygen that they have to use. They are replaced when they wear
out.
The problem is that if they wear out faster than they can be replaced
you
have a big problem (low ATP).
As we age, the ability of the cell to use it's nuclear DNA to crank
out the
proteins that will be needed to form a new mitochondria declines. If
this decline in the rate at which new mitochondria are turned out also
occurs with
increased free radical formation because the antioxidant defense
system is also getting old, you have a problem.
Getting antioxidants into the mitochondrial to protect it is extremely
hard to do. Lipoic acid seems to be able to do this. If it does it
in rats it's going to do it in human mitochondria.
Greg Watson
Here is a bit of very important information which shows for the first
time a pathway has been found to mop up free radicals at source (the
mitochondria). The implication are very wide spread and the two
supplements used are very available and low cost. I already use both
and will do further research to determine the effective dose for
humans.
Note the statement:
"The researchers estimate that the effect on the rats was the
equivalent making a 75 to 80-year-old person act middle-aged."
While I still believe a CRONing diet and exercise are highly effective
in an anti-aging protocol, this research is exciting.
http://news.bbc.co.uk/hi/english/health/newsid_1827000/1827008.stm
Tuesday, 19 February, 2002, 00:09 GMT
Hopes grow for anti-ageing drug
Scientists have rejuvenated ageing rats by giving them a cocktail of
dietary supplements. The breakthrough raises hopes that it might one
day be possible to develop an anti-ageing drug for humans. These old
rats got up and did the Macarena
The researchers gave a combination of two natural chemicals available
in health food stores to the animals - which were in the rat
equivalent of their seventies. Lead researcher Dr Bruce Ames, of the
University of California at Berkeley, said the results were
astonishing. He said: "With the two supplements together, these old
rats got up and did the Macarena. "The brain looks better, they are
full of energy - everything we looked at looks more like a young
animal." The animals' memories were also significantly improved. The
researchers estimate that the effect on the rats was the equivalent
making a 75 to 80-year-old person act middle-aged.
Found in the body
The chemicals used in the experiment were acetyle-L-carnitine and
alpha-lipoic acid, both of which are normally found in the body's
cells and research like this provides the first step to developing
treatments that will help to improve health in later life
Acetyle-L-carnitine is sold as an energy-booster and alpha-lipoic acid
as an antioxidant with anti-ageing effects. The combination of the two
chemicals has now been patented by the University of California. A
company set up to exploit the patent, Juvenon, is already conducting
human clinical trials.
Three research papers on different animal studies of the chemicals
have been published in the journal Proceedings of the National Academy
of Sciences. The studies probed the biochemical action of the
supplements, compared the behaviour of old and young rats, and tested
the memory of animals fed the compounds.
Cell power house
The researchers found that the two chemicals in combination have a
positive impact on mini-organs within the body's cells called
mitochondria. Mitochondria generate energy within the cells, and
research has suggested that their deterioration is an important cause
of ageing. The problem seems to be that the very process of creating
energy generates molecules called free radicals, which have a deeply
destructive effect on the way cells work. The supplement combination
was found to mop up the free radicals in mitochondria. It also boosts
the activity of an enzyme fundamental to the energy-creating process.
The research also showed that mitochondria in brain cells important to
memory were less damaged by radicals in animals fed the supplements.
Important research
Caroline Bradley, of the charity Research into Ageing, told BBC News
Online that the study was clearly important. She said: "The big step
forward is that they have found a way of getting anti-oxidant into the
mitochondria itself. Getting past the mitochondrial membrane has been
the main challenge." She added that it was early days for the research
but that it was the first step towards improving human health in later
life.
=======================
For all those interested in the free radical theory of aging, there is
a very good collection of full text papers available on the Juvenon
site.
http://www.juvenon.com/html/Science.html
I await the results of the 19 week trial they started in Feb 2001.
http://www.juvenon.com/html/Science_Clinical_Trials.html
Here is the Juvenon patent # 6,335,361
Goto the US patent search engine at:
http://patft.uspto.gov/netahtml/search-bool.html
type in the above number and read the patent.
United States Patent 6,335,361
Hamilton January 1, 2002
Method of treating benign forgetfulness
Abstract
Disclosed herein are methods to treat cognition disorders,
particularly those associated with aging.
The method comprises administering a combination of a carnitine and an
oxidant.
Preferably the oxidant is thioctic acid .
Preferably 0.12 grams to 3 grams of carnitine (particularly ALC) and
0.12 to 1.5 grams of alpha lipoic acid are administered.
Optionally, coenzyme Q and/or creatine also are administered.
Preferably 10 mg to 500 mg/day of coenzyme Q10 and 1 to 30 grams/day
of creatine are administered.
The same method can be used to treat cognition deficits associated
with carbon monoxide poisoning, mild traumatic brain injury, Type 2
diabetes mellitus, obsessive-compulsive disorder, environmental toxin
exposure, and other conditions.
========================
Note: A patent does NOT stop you using these supplements for your own
use.
From the patent (6,335,361), here is a suggested dosage based on
averages.
Acetyl-L-Carnitine (ALC) - 1.5 g (0.12 to 3 g)
Alpha Lipoic Acid (ALA) - 0.8 g ( 0.12 to 1.5 g)
CoQ10 - 250 mg (10 to 500 mg)
Creatine - 15 g (1 to 30 g)
I would suggest dividing this into 3 doses taken 3 times a day:
Acetyl-L-Carnitine - 500 mg
Alpha Lipoic Acid - 250 mg
CoQ10 - 80 mg
Creatine - 5 g
The ALC, ALA & CoQ10 should fit in a standard "00" capsule and the
Creatine is about 1 teaspoon.
Costing based on Beyond a Century prices:
$0.44 for 1.5 g ALC
$0.30 for 0.8 g ALA
$0.70 for 0.25 g CoQ10
$0.38 for 15 g Creatine
-------------------------------
$1.82 per day
========================
Good health & long life,
Greg Watson,
http://optimalhealth.cia.com.au
DB
> Hi All,
>
> Here is a bit of very important information which shows for the first
> time a pathway has been found to mop up free radicals at source (the
> mitochondria). The implication are very wide spread and the two
> supplements used are very available and low cost. I already use both
> and will do further research to determine the effective dose for
> humans.
Is the mitochodria the main source of free radicals generated within the
body? What are the main other sources?
Dave (soon to be biochem student)
Martin Banschbach
> Is the mitochodria the main source of free radicals generated within the
> body? What are the main other sources?
>
> Dave (soon to be biochem student)
Mitochondria produce superoxide free radicals. Everytime electrons
move to oxygen in mitochondira this happens. There is an estimate of
how much is
formed in each mitochondria each day and how much of this gets out but
that info is not stored in my memory banks or in my class notes.
All superoxide is produced by Coenzyme Q10. If you increase Q10 you
increase
superoxide production. Mitochondrial DNA codes for superoxide
dismutase and
this manganese requiring enzyme takes out most of the superoxide
formed.
Breast cancer and prostate cancer cells lack mitochondrial superoxide
dismutase
(gene mutation took it out) and giving these cancer cells Q10 kills
them in vitro.
Since our immune system also forms superoxide the total body load is
probably pretty high. I have seen estimates of the amount of each
free radical species
that humans produce each day and I know that superoxide is near the
top but I think nitric oxide is first (don't quote me on that).
Superoxide is a pussy cat compared to some of the other free radicals
but it
does appear to be the one that wears out the mitochondria.
Both exercise and Q10 supplementation appear to induce more formation
of mitochondrial superoxide dismutase but we know that some cancer
cells can not do this. Both hyperbaric oxygen and regular exercise
have been proposed as
ways to kill the cancer cells that can no longer form mitochondrial
superoxide
dismutase but you are not going to find literature support for this
claim. You will find literature support for high dose Q10 completely
eliminating metastatic
breast cancer in women who failed all conventional treatments for
breast cancer but none of these studies have been done in the U.S.
Both carnitine and lipoic acid are anti-oxidants and both can get into
the mitochondrial matrix where superoxide is formed (for carnitine you
have to use
acetyl-carnitine). Carnitine can not cross the blood-brain barrier
but acetyl-carnitine can. There is speculation that acetyl-carnitine
will help prevent the
development of Alzheimer's.
If you are eating animal foods you already have a very high level of
acetyl-carnitine in your body. Animal foods also give lipoic acid but
to push the level high enough to force it into mitochondria and have
it free to act as an anti-oxidant you have to use a supplement.
Lipoic acid does not extend the maximum life span of rats and mice to
any significant extend even if you really push it. I am going to
start a thread on mercaptoethanol. This is another thiol just like
lipoic acid is a thiol but it can move places that lipoic acid can't
move. It's thiol is also much more reactive than the thiols in lipoic
acid. I will cite numberous animal studies where mercaptoethanol does
greatly and significantly extend the maximum life span of lab animals.
Mercaptoethanol also removes glucose from glycosylated protiens (I
will also cite these papers).
Both are probably need to extend life span. Lipoic acid can handle
some free radicals but it can not get glucose off glycosylated
proteins.
lad
> Evolution has no reason to want you to age more rapidly when you could be
> (at a small synthetic cost) age more slowly.
I'm no Steven J. Gould :-), but the conventional wisdom has always
been that nature/evolution doesn't care a rat's rectum about how long
you live. Just as long as you can crank out and successfully rear
enough offspring.
If we truly "lived in nature" then we'd all be moms n' dads in our
teens (probably after a parentally arranged pairing). We'd have
grandkids in our thirties. Then we would all check-out in our forties,
if we're lucky.
Having the wisdom and support of gramps or great-grand-mom may help
the provision/procreation network, but it doesn't seem necessary.
(Anyway, our present arrangement sure beats having your female partner
tearing off and eating your skull right after "your first time").
It is cultural evolution (i.e. science) that has displaced natural
selection and lengthened our lives. We figured out a few things
regarding sanitation, antibiotics and canned food. Now, for our next
trick, we have to get busy jiggling all those cells and genes.
All the same, good luck to Juvenon. Even though the ALA/ALC--(and
sometimes CoQ10, DHEA, etc) combo formula has been sold for a while by
different companies. NOW, if they could just come up with a perfected
ALC that wouldn't make me so irritable!!! :-)
LS
Steve Harris
news:1e1efc6b.02022...@posting.google.com...
> If you could slow aging this easily, why doesn't your body do it?
> > Evolution has no reason to want you to age more rapidly when you could
be
> > (at a small synthetic cost) age more slowly.
>
>
> I'm no Steven J. Gould :-), but the conventional wisdom has always
> been that nature/evolution doesn't care a rat's rectum about how long
> you live. Just as long as you can crank out and successfully rear
> enough offspring.
Sure, and aging obviously causes problems with that. If you stayed
physiologically 20 forever, you could obviously raise a lot more children
until the sabertooth or bad hunting season or placenta previa or whatever
got you.
> If we truly "lived in nature" then we'd all be moms n' dads in our
> teens (probably after a parentally arranged pairing). We'd have
> grandkids in our thirties. Then we would all check-out in our forties,
> if we're lucky.
People checked out in their 40's BECAUSE of aging. Otherwise, those that
made through accident and famine and into their 40's would have had the
exact same individual mortality risk as at age 15. Which would have been
high in the Paleolithic, to be sure, but still a lot lower than it actually
was, for people who made it to (what we now think of as) middle age.
> Having the wisdom and support of gramps or great-grand-mom may help
> the provision/procreation network, but it doesn't seem necessary.
No, but it's helpful. And besides, this is "group-selection." It's a weak
force compared with individual selection, and is powerless so long as
there's much crossbreeding between groups (which there must've been for
humans, since we're all related pretty closely, as shown by our mitochondial
genes). And aging is obviously strongly bad for the reproductive success of
*individuals.* The only reason we have it must be that the "cure" or
"postponement" of aging must involve something like need for a lot more
calories and nutrients for repair, which is/was equally bad for the
individual, in the face of externalities which made age-independent death
rates high (famines, jaguars, fights, childbirth, infections that kill even
15 year-olds, etc). Why should you spend a lot to do maintenance on a car
(change your oil, etc) in a city where people drive crazily and you're
likely to be totaled in less than year? We see in birds and bats that nature
WILL delay aging if it's given good reason to. In other words, you cannot
suggest that we humans are designed deliberately to age as soon as we've
reproduced, because you can see from birds and bats that nature doesn't have
to design animals that way. You're only designed to crap out after the
first reproduction *if* the odds are bad of you making it to the second set
are crumby, for *non-age-dependent* reasons. If humans could remain
youthful (i.e., reproductive longer) by producing a little more lipoic acid
and acyl carnitine, they'd surely have evolved to do it.
Hmmm. Which brings up the interesting idea that if these things only work to
make the very elderly look more middle-aged, then nature might indeed not
have bothered. Evolution truly would have little incentive then, except
possibly through the weak grandmother-group-selection effect, for which you
only need a small percent of survivors anyway. We should remember that an
honest to god *anti-geriatric* chemical need not be an across-the-life-span
anti-aging chemical...
Which brings up yet another point, and that is that these things were tested
in mice, which don't need wise grandmothers. It may well be that we'll find
that some subset of humans (enough to ensure a few vigorous oldsters in
every tribe) already have learned the ALC+lipoic trick, and already do what
they're doing to mice. This subset might be small or large-- who knows? If
the trick is easy, it might be large. As in, most of us.
> (Anyway, our present arrangement sure beats having your female partner
> tearing off and eating your skull right after "your first time").
As opposed to her tearing your head off when the kids hit 4-to-6? Which is
the way we humans do it now? <g>
> It is cultural evolution (i.e. science) that has displaced natural
> selection and lengthened our lives.
Yes.
> We figured out a few things
> regarding sanitation, antibiotics and canned food. Now, for our next
> trick, we have to get busy jiggling all those cells and genes.
Yes.
> All the same, good luck to Juvenon. Even though the ALA/ALC--(and
> sometimes CoQ10, DHEA, etc) combo formula has been sold for a while by
> different companies. NOW, if they could just come up with a perfected
> ALC that wouldn't make me so irritable!!! :-)
I think it's likely to be snake oil, or else something that only works on
the "prematurely" frail elderly-- but I applaud the spirit and the attempt!
This stuff gets people in the proper mindset to make the attack (which is
ridiculously badly funded now), and that has to be good.
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]."
LS
Martin Banschbach PhD
> to run another small trial in mice from my small colony, which already
will
> start out old (32 months). I'll pre-stratify them by weight and
appearance,
> then randomize them to 1 ppt CoQ10 or not. We'll see if I get similar
> effects.
>
> SBH
Steve,
If you are doing this inhouse, try mercaptoethanolamine. Mercaptoethanol
has been done many times with very good results but mercaptoethanolamine has
never been done (no published data that I could find). All of the data for
mercaptoethanolamine is classified U.S. Army data. If what these documents
say (what they said when I read them in 1982) is true, you are going to get
at least a doubling of the *maximum* life span of mice. The LD50 for mice
is 625 mg/kg orally and 250 mg/kg i.p. For mercaptoethanol the LD50 is
344.8 mg/kg orally and 322 mg/kg i.p.
Mercaptoethanolamine is supposed to have a thiol that is more reactive than
the thiol in mercaptoethanol and more toxic but it's only more toxic if
injected.
When I was at LSU I could keep as many mice and rats as I wanted without any
cost to me but here you have to pay even if you have no outside grant.
As an old fart, I've been eased out to let the younger non-tenured faculty
have the lab space they need to get tenure. I no longer have a lab or a
technician so I'm left trying to drum up business on the coat-tails of other
faculty. Either of these very active thiols is going to work very well in
mice but Q10 is not toxic while both of these are (any real human
potential?). If anyone does this kind of study and then shows that either
of these can be formed naturally when ethanol comes into an animal is going
to make quite a name for themselves. As sharp as Bruce Ames is I never
could figure out why he never picked up on the radioprotective drug angle.
Keeping the little buggers around that long can get expensive unless your
in-house animal care people cut you a break on animal costs.
Coenzyme Q10 has been tried many times and it is just is not going to work.
--
Marty B. "You are what you eat."
http://centernet.okstate.edu/nutrition/index.html
The above website is for educational purposes
only. Material in this website and posted material
represents the opinion of Martin Banschbach,
Ph.D. and does not reflect Oklahoma State
University policy or position on nutrition.
Issues regarding the diagnosis and treatment
of human disease can not be addressed
by material in the above website or by
Martin Banschbach, Ph.D.
Any comments made by Martin
Banschbach, Ph.D. are invalid unless
confirmed by your personal physician.
Steve Harris
news:a50nos$9a...@news.cis.okstate.edu...
> Steve,
>
> If you are doing this inhouse, try mercaptoethanolamine. Mercaptoethanol
> has been done many times with very good results but mercaptoethanolamine
has
> never been done (no published data that I could find).
COMMENT:
You probably missed:
J Gerontol 1990 Sep;45(5):B141-7
Dietary restriction alone and in combination with oral
ethoxyquin/2-mercaptoethylamine in mice.
Harris SB, Weindruch R, Smith GS, Mickey MR, Walford RL.
Department of Pathology, University of California, Los Angeles.
To investigate effects of dietary caloric restriction (DR) combined with
antioxidant feeding, long-lived hybrid mice were divided into four dietary
groups at weaning, and followed until natural death. Groups "C" and "R"
received control (97 kcal/wk) and restricted (56 kcal/wk) diets
respectively. Groups "C+ alpha ox" and "R+ alpha ox" received C or R diets
supplemented with an antioxidant mixture (2-mercaptoethylamine plus
ethoxyquin). R mice (mean life span 41 months) significantly outlived the
other three groups (mean life span 30-34 months). Hepatic degeneration and
increased hepatoma in the R+ alpha ox group suggested unusual hepatotoxicity
of this regimen. Antioxidants had little effect on splenic cell mitogen
response in similarly fed mice sacrificed at 12-15 months. Gompertz analysis
suggests that the beneficial effect of DR may be due to reductions in
initial vulnerability or rate-of-aging parameters, or both, and that the
relative influence of each factor may vary with animal strain and DR
protocol used.
PMID: 2394907 [PubMed - indexed for MEDLINE]
Notice the authors. It's true this study used a combination of ethoxyquin
AND 2-mercaptoethanolamine, aka cysteamine, but other people have done
cysteamine alone to death, and it doesn't work in long lived strains. Nor
did it for us. Harmon's original free radical theory of aging was kicked off
with some cysteamine studies in short lived mouse strains fed ad lib, where
it squares the curve in a few strains, but not convincingly (works in some,
not others; doesn't increase max life span).
> All of the data for
> mercaptoethanolamine is classified U.S. Army data. If what these
documents
> say (what they said when I read them in 1982) is true, you are going to
get
> at least a doubling of the *maximum* life span of mice.
I don't believe it. However, somebody may have some data where they fed
cysteamine to mice and they got a life span extension because the animals
hate the smell of the stuff and don't eat their food. Thus, this is just a
complicated form of dietary restriction. "Urg, this food smells like shit.."
The army looked at cysteamine and also its phosphate conjugate WR-1065 (WR
standing for Walter Reed) as possible radioprotectants in soldiers, since
they work modestly well in mice. That stuff is published. The army's best
radioprotectant was not this compound, but actually the thiol WR-2721, aka
ethiophos, which actually eventually made it into pharmaceutical use as
"amifostine", a compound which protects salivary glands in people undergoing
radiation for head and neck cancers where the salivaries are in the field.
Long before this, in the early 1990's, I had the idea what perhaps WR-2721
would be an anti-aging compound. I got hold of it, ran a dose-tox study, and
when I found some appropriate doses (which didn't induce weight loss) I ran
lifespan studies at those doses. Result: zip. It neither lengthened nor
shortened lifespan in my long-lived mildly restricted model. I never
published that (I may someday) because about this time I was beginning to
come to the conclusion that trying to fix aging with one or another single
chemical is about like trying to make your car immortal by changing its
sparkplugs more often.
As for 2-mercaptoethanol, it's been done by somebody else, and it increased
max life span in rodents by just a touch-- the only chemical I know of in
any study that has done this convincingly, without weight loss. Supposedly--
I'm not sure I believe that part, given its nature. This chemical, as
somebody has mentioned, has a rotten egg mercaptan smell so evil and nasty
that nobody's ever seriously suggested further exploration of it. The chief
charm of the army's WR phosphated thiols is that they didn't stink much.
2-ME might prolong your life a bit, but at the price of being a permanent
social outcast. The Frankenstein myth indeed!
BTW, a few mice in my ethoxyquin/cysteamine group died with their body
cavities full of blood. I think that was the cysteamine. I've found other
cysteine feeding studies where aortic rupture was induced by overdose on
thiols, thought to be due to mercapto-chelation of copper, followed by
copper dependent collagen synthesis defects. My guess is that cysteamine
does the same. I wanted to put that in the paper, but Walford thought it
was too much of a stretch for our data, and nixed it. But I wouldn't eat
short chain thiols indiscriminately in huge doses, for long periods. You
might end up with your aorta going balooey.
Alf Christophersen
<mba...@osu-com.okstate.edu> wrote:
>As an old fart, I've been eased out to let the younger non-tenured faculty
>have the lab space they need to get tenure. I no longer have a lab or a
I just wonder how you manage to eat such real farts as mercaptoethanol
??
Martin Banschbach
I've got the abstracts on mercaptoethanol at work and still
plan on posting a discussion of this thiol.
The idea of the smell restricting food intake never occurred
to me. I've seen it done both ways (from the abstracts that I've
read), put it in food or put it in water. Rats already have a problem
with solute load (renal failure late in life from what I understand)
and the water may not work that well. I don't know if mice have the
same problem (kidney failure late in life). Watching the rat protein
intake
seems to help with their longevity but it's not pushing it past what
would
be expected.
I can tell you that all of the abstracts that I did print out only
indicate mean and maximum extension of life span and never indicated
the degree of extension for either one, only that the effect was
significant. Thiolamines were supposed to be the best
radioprotectants eventough they have substantial potential
toxicity. But cysteine has an LD50 too.
I had no idea that you were this up on the thiols. I guess that if
you
had ever come across any data suggesting that ethanol could be
sulfated
in the liver of any animal to form mercaptoethanol you would have
mentioned this.
The way I understand the whole free radical picture is that hydroxyl
free radicals are not present in the amounts that other free radicals
are in human tissues or for that matter mice and rat tissues.
The goal of the radioprotectant research as I understand it is to come
up with chemicals that can handle hydroxyl free radicals and that can
be consumed by humans. Soldiers sometimes object to the immunizations
that they have to get, if I had to drink mercaptoethanol, I think I
might
throw it up as fast as it went down. I still can't image anyone
drinking
enough of this stuff to kill themselves but DMSO is also pretty foul
and
people were drinking it, and also dying from that intake.
Humans appear to be the only animals on this planet that will
purposely go out of their way to do something really stupid. I'd say
smoking is in the same class as drinking mercaptoethanol but I've seen
the Chimps at the Tulsa Zoo pick up lit cigarettes and smoke them.
It's only the dominate males that do
it and the Zoo had to construct a mesh enclosure to keep the human
jerks from throwing cigarretes into the Chimp area. They put up a
high fence but found out that some guys were so good that they could
still get cigarretes to the Chimps. They have a very nice set up that
cost an awful lot of money to move the chimps from their inside
display area to a large island on the Zoo grounds. They had a waist
high fence around it when it first opened and then went to what I
guess is a 10 foot fence and finally put a mesh over the whole area.
I guess that guys were climbing up on the fence to throw the
cigarettes. If they landed on the viewer side of the water that goes
around the whole island, no Chimp would go through the water to get
it. If you could get it over the water, then you saw a real good
Chimp fight over who was going to smoke it. I never threw any
cigarettes at the Chimps and I kept my son from doing it.
If you can identify the free radical that is doing most of the damage
it
appears possible to limit some of that damage.
For reperfusion, I really don't know if there is a single free radical
that
does most of the damage but I have read the abstracts where specific
chemicals
are being tested. I never understood the need for the number system
other than
that drug companies seem to be involved and they like to give their
new drugs
numbers as they are being tested.
The antioxidant mix that LEF uses should have handled just about all
of the
known free radicals but preloading through diet is unlikely to be as
effective
as reperfusion with antioxidants in the perfusate.
I've used C in our hypobaric chamber with human volunteers and drew a
big zip. The antioxidant mix also got a big zero during brain anoxia
in rats. We just met with a creatine pusher yesterday and are
thinking about trying to do something with either Alzheimer's patients
or the hypobaric chamber again.
This guy who is actually an M.D. who has done a lot of work with
creatine and started his own company after he retired from the OU
medcial school. He has a creatine gum that can get the levels up in
blood better than the powders or the pills. He also has a waffer that
disolves in the mouth which is what we would have to use for
Alzheimer's patients.
I know what creatine does in muscle but we told him we would have to
confirm an
action in brain (or at least that it gets across the blood brain
barrier) before we would commit to studying it. He said that there is
published data showing that creatine supplementation helped with brain
concussions. I have to check that out too. He made sure that we knew
that the wrestling deaths were not caused by creatine. Heck, I
already knew that, it was dehydration and creatine is not a naturetic
like caffeine is.
If you have any good ideas on how we can use either our hypobaric or
hyperbaric chambers, let me know. I know how Michael Jackson uses his
hyperbaric oxygen chamber so I'm not interested in that particular
use. We are still trying to set up a study with cancer patients
getting radiation treatment but the issues of hyperbaric oxygen
toxicity may be too hard to overcome.
Martin Banschbach Ph.D.
>??
I have an inquiring mind. I think it's what got me through grad school. I
always wanted to know why. I never was content to learn something just because
I had to. If I could not understand why it was important to know it, I would
force myself but I did not like it. We had to learn the name of every
biochemist that every got a nobel price and what area of research they got it
for. It was part of the prelim. Gag me with a spoon.
When we got into essay questions, I found that my knack for trying to
understand things probably saved my butt. One of my good friends in grad
school was a real good note taker and a real good memorizer. He never made it
to a masters. After 4 years they finally washed him out. If you wanted to
know something that was covered in class, he was the guy to ask. But he never
could put facts together and come up with any meaning from those isolated
facts.
I actually had a chance to hear both Pauling And Krebs talk right after I got
my first academic position. It was a mentoring program, the old guys teaching
the new guys the meaning of science.
There were actually 4 speakers, I only remember what Pauling and Krebs said.
The other two pretty much went over their claim to fame. Pauling and Krebs
spent almost all of their hour talking about an inquiring mind. In different
ways they both said that tunnel vision was only for average scientists. If you
wanted to be good, resist the urge to tunnel all of your time and energy into a
very narrow area.
Since I had to try to get my first NIH grant I never gave what they said much
thought. As I matured, I realized that they were right.
Teaching human nutrition all by myself and also teaching all of biochemistry
all by myself when the other biochemist died in a hunting accident made me open
my view even more. Since Oklahoma was hit with the oil bust in the early 80's,
I had to wait three years before another biochemist was due to be hired. I
actually got two hired eventhough I was told I could only hire 1. I brought 1
in on a tenure-track position and another in on a research appointment (I'm a
good salesman). Gary is now our Director of Research and is soon to be a
tenured full professor of Biochemistry. I had to sell both Gary and our
administration on hiring a research scientist. If you know anything about
academics you know that a research position is often the kiss of death. You go
from being a postdoc to a research scientist, big deal.
I've gotten so good at selling ideas that I have to be real careful that I
don't end up selling myself a bill of goods.
When Steve raised the issue of vodka and whether or not it could also have a
health benefit, my mind reverted back to mercaptoethanol. It's a wild idea.
B12 synthesis by bacteria in the human gut is a wild idea too. Pauling had
some pretty wild ideas too. I'm sure he had some people to bounce them off
before he went public with them.
I like to brain storm. I used to do it inhouse. Now I do it in UseNet. Every
once in awhile people still think that I might have something left in me and I
get invited to a brain storming session like what happened yesterday with
creatine.
All the young guys with labs get together to exchange ideas just like I used to
do. I'll reach the rule of 80 in a little over 1 year and I can collect full
retirement pay from the State system. With my TIAA-CREF, I'll be in pretty
good shape as long as I don't have to spend anymore money on my son. Everybody
else has gotten out as soon as they can. I told my wife last night that I
think that I like teaching too much to go out when I can.
I've seen old guys hang around too long in academic institutions. I had to
take their classes as a graduate student. I swore back then that I would never
subject any student to what I had to put up with.
I think that as long as I can still come up with wild ideas, I'll stay around
in academics for a little longer, assuming that my lifestyle does not jump up
and bite me.
Marty B "You are what you eat"
Alf Christophersen
<sbha...@ix.RETICULATEDOBJECTcom.com> wrote:
>BTW, a few mice in my ethoxyquin/cysteamine group died with their body
>cavities full of blood. I think that was the cysteamine. I've found other
>cysteine feeding studies where aortic rupture was induced by overdose on
I would rather blame ethoxyquib fir that, It is a very dangerous
compound that if migrating into mithochondria, it hooks up as
coennzyme Q, but produce only free radicals and do not deliver any
electrons to the electron flow that otherwise Q10 joins into.
Steve Harris
news:20020221112733...@mb-mv.aol.com...
> I actually had a chance to hear both Pauling And Krebs talk right after I
got
> my first academic position. It was a mentoring program, the old guys
teaching
> the new guys the meaning of science.
>
> There were actually 4 speakers, I only remember what Pauling and Krebs
said.
> The other two pretty much went over their claim to fame. Pauling and
Krebs
> spent almost all of their hour talking about an inquiring mind. In
different
> ways they both said that tunnel vision was only for average scientists.
If you
> wanted to be good, resist the urge to tunnel all of your time and energy
into a
> very narrow area.
COMMENT: Yes. Whereas, if you'd like to get funded, and an academic
position in which you can actually advance to tenure-- in other words, if
you'd like to eat and pay the mortgage from science-- then it's much better
to specialize like hell.
Then you go to meetings where the real thinking is done, and the guys who
like to write reviews (their specialty) suck up ideas "out of the air", put
them together, and in general do the synthetic work of science. And you can
do that also, if you have any spare time between writing one more boring as
hell paper.
Alf Christophersen
<sbha...@ix.RETICULATEDOBJECTcom.com> wrote:
>Notice the authors. It's true this study used a combination of ethoxyquin
>AND 2-mercaptoethanolamine, aka cysteamine, but other people have done
Cysteamine is one of the main sources for taurine formation. It is
quickly oxidized to hypotaurine, a strong antioxidant, which in turn
is oxidized to taurine
(RSH -> RSO2H -> RSO3H)
Nelson J. Navarro
the chemical recently identified by Bruce Ames as having some potential
anti-aging properties.
Take a look at the following:
J Biol Chem 2000 Mar 10;275(10):6741-8
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]
******************************************************************
FASEB J 2001 Oct;15(12):2196-204
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
jannis
please tell us more about mercaptoethanol. Sounds interesting....
mbans...@aol.com (Martin Banschbach) wrote in message news:<cba7fed1.02022...@posting.google.com>...
lad
> physiologically 20 forever, you could obviously raise a lot more children
> until the sabertooth or bad hunting season or placenta previa or whatever
> got you.
I think the point of it all is that, (in the strictly mechanical,
random, evolutionary sense), nature doesn't need to make any species
more long-lived IF it already rears enough kids to replace and
multiply itself (careless millions of offspring in the case of
insects, a handful in the case of careful humans).
Some species (lobsters, orange roughy, rock fish) seem almost
arbitrarily gifted with being long-lived, long-teleomered &
non-senescent. And, also - (in the strictly purposeful, ordered,
creationist sense) made delicious, to show that the Creator must have
a gourmade sense of justice! :-)
>
> People checked out in their 40's BECAUSE of aging. Otherwise, those that
Most of the longer lived species have had extra eons to adapt
compared to us primate newbies. Instead, we got a rapidly developed
brain that made for a cultural adaptation toward longevity . Early man
died sooner not because of a lesser evolved "aging" effect. He died
because he hadn't yet invented (or learn to value) better food
storage, crop planning, varied diet, sanitation, and predator defense
(both the saber-toothed kind and the more voracious microbes).
Nature had no time, nor reason, to endown man with longer telomers or
an enhanced ALC/ALA metabolism. Us little buggers were already killing
everything else, eating & reproducing well and using up resources.
Ultimately, longevity will be understood as an engineering problem.
ALC/ALA is just another early, flint tool pointing to the solution.
"Natural" and chemical tools may give away to nanotech and waveform
solutions. Entrophy is always inevitable, but aging's multiple causes
will be treated just as someone maintains the many needs of a beloved
antique car (even when it requires near total renovation or
duplication of original parts).
Alex Brands
> Snobs be gone!
>
> Once upon a time, our fellow lad
> rambled on about "Re: Aging and ALC/lipoic acid (was: alpha lipoic
> acid eliminates wrinkles?)."
> Our champion being bored in sci.med.nutrition retorts, thusly ...
>
> >> Sure, and aging obviously causes problems with that. If you stayed
> >> physiologically 20 forever, you could obviously raise a lot more children
> >> until the sabertooth or bad hunting season or placenta previa or whatever
> >> got you.
>
>
> A long life is a disadvantage in Darwinian Evolution.
>
> The most successful life form on planet earth are the Insects. And,
> Insects have extremely short life spans. :-)
Perhaps they are the most successful animal life form, but they don't come
close to bacteria. Of course, bacteria have an even shorter generation
time.
Alex
Martin Banschbach PhD
> position in which you can actually advance to tenure-- in other words, if
> you'd like to eat and pay the mortgage from science-- then it's much
better
> to specialize like hell.
You are absolutely right Steve. I think that the point that Kreb's and
Pauling were trying to make is that science is a lifetime profession. To
survive (and even to win a Nobel prize) you have to focus all of your time
and energy into a very narrow area to beat all of your competitors to the
prize at the end of the tunnel. Their view is that this is average science
even if you are lucky enough to hit the jackpot and win the Nobel prize.
Great science comes later in life where the security of tenure allows you to
spread your wings. Most can not break out from the tunnel vision that has
to be used to survive at all in science. Both men spent their later years
in life spreading their wings. Pauling just spread his a little further out
than Kreb's did.
If you want to continue to get grants, you have to focus. I doubt is too
many scientists have the brain power to get involved in the review of
science while also tracking down the "truth" of science.
Science needs both. Good fact finders and good reviewers who can take all
the isolated facts and try to make some sense out of it. Pauling and Krebs
basically said that the great scientists where both. The very best minds
are needed to track down the facts, if those same great minds can move over
into understanding what all the isolated facts mean, science wins and great
men are born.
I'm neither. I gave the fact finding my best shot and had some success. I
can't remember what the odds are of actually getting a Nobel prize in
medicine are but it's probably close to the odds of getting hit by
lightening. I haven't written any review articles other than the review of
cancer for a fitness book. If I can't sniff out a hot lead on original
research pretty soon, I may switch to writing review articles.
Thomas Carter
> "lad" <ch...@my-deja.com> wrote in message
> news:1e1efc6b.02022...@posting.google.com...
> > If you could slow aging this easily, why doesn't your body do it?
> > > Evolution has no reason to want you to age more rapidly when you could
> be
> > > (at a small synthetic cost) age more slowly.
> >
That is clearly the conventional wisdom, and I almost always bet on
the favorite. In health matters I bet her to show when possible. But
the fickle nag frequently loses. (at the track and in medical science)
There are many possible reasons why evolution might want us dead
early. IE, Grand, or Greatgrandmother might be a breeding ground for
microbes that selectively take out her progeny. NB that many social
animals have the custom to wander off and die alone. Nature might have
terminated many a promising line for the sin of outliving their immune
system. Even with a sound immune system she could take them out due to
any age related stress which depresses it. Several other possibilites
come to mind quickly. I bet the group could come up with quite a few.
It might be fairly hard without procucing anti-survival side effects.
See this paper we got from Aubrey.
"High-level MnSOD expression in B6 animals was associated with small
size, male infertility, and decreased female fertility. These features
are absent on the D2 background and indicate that high levels of MnSOD
activity may interfere with normal growth and fertility. PMID:
11595386"
While this would be fatal for my group. It would be fine for me. I
have already grown too much and infertility would just mean less
chance of child support payments. Germ line cells surely have better
anti-oxidant defenses than stromal cells. What is good for the goose,
may be bad for the spermatazoa.
I think evolutionary theory has far to many unknowns to be used as
an effective tool in making molecular biology predictions except in
some special and obvious cases.
Thomas
Thomas Carter
> news:1e1efc6b.02022...@posting.google.com...
> > If you could slow aging this easily, why doesn't your body do it?
> > > Evolution has no reason to want you to age more rapidly when you could
> be
> > > (at a small synthetic cost) age more slowly.
> >
That is clearly the conventional wisdom, and I almost always bet on
the favorite. In health matters I bet her to show when possible. But
the fickle nag frequently loses. (at the track and in medical science)
There are many possible reasons why evolution might want us dead
early. IE, Grand, or Greatgrandmother might be a breeding ground for
microbes that selectively take out her progeny. NB that many social
animals have the custom to wander off and die alone. Nature might have
terminated many a promising line for the sin of outliving their immune
system. Even with a sound immune system she could take them out due to
any age related stress which depresses it. Several other possibilites
come to mind quickly. I bet the group could come up with quite a few.
> > I'm no Steven J. Gould :-), but the conventional wisdom has always
It might be fairly hard without procucing anti-survival side effects.
Brandon Van Every
"Martin Banschbach PhD" <mba...@osu-com.okstate.edu> wrote in message
news:a5610g$8a...@news.cis.okstate.edu...
>
> I'm neither. I gave the fact finding my best shot and had some success.
I
> can't remember what the odds are of actually getting a Nobel prize in
> medicine are but it's probably close to the odds of getting hit by
> lightening. I haven't written any review articles other than the review
of
> cancer for a fitness book. If I can't sniff out a hot lead on original
> research pretty soon, I may switch to writing review articles.
Science, a hit-driven industry! Just think of what you have in common with
those of us chipping away at entertainment....
--
Cheers, www.3DProgrammer.com
Brandon Van Every Seattle, WA
20% of the world is real.
80% is gobbledygook we make up inside our own heads.
MattLB
John 'the Man' wrote:
> >> Sure, and aging obviously causes problems with that. If you stayed
> >> physiologically 20 forever, you could obviously raise a lot more children
> >> until the sabertooth or bad hunting season or placenta previa or whatever
> >> got you.
>
> You got it backwards.
>
> A long life is a disadvantage in Darwinian Evolution.
>
> The most successful life form on planet earth are the Insects.
Bacteria are the most successful form of life on the planet. By a long way.
MattLB
Steve Harris
news:<a50oui$nc5$1...@nntp9.atl.mindspring.net>...
>> "lad" <ch...@my-deja.com> wrote in message
>> news:1e1efc6b.02022...@posting.google.com...
>> > If you could slow aging this easily, why doesn't your body do it?
>> > > Evolution has no reason to want you to age more rapidly when you
could
>> be
>> > > (at a small synthetic cost) age more slowly.
>> >
>Hi,
>That is clearly the conventional wisdom, and I almost always bet on
>the favorite. In health matters I bet her to show when possible. But
>the fickle nag frequently loses. (at the track and in medical science)
>There are many possible reasons why evolution might want us dead
>early. IE, Grand, or Greatgrandmother might be a breeding ground for
>microbes that selectively take out her progeny.
That's ridiculous. If you've ever had kids you know how much more likely it
is to be the other way around. In any case, it relies on a kin selection
argument, and these are never good when they rely on having a weak kin
selection advantage (or disadvantage) overpowering a direct disadvantage to
the breeding of the individual (which aging always is). Any increased risk
you have to dying in pregancy or childbirth after 18 is due to aging. If
nature could take care of this easily, it would.
--
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.
Thomas Carter wrote in message ...
Steve Harris
But they don't really age.
Steve Harris
>I think the point of it all is that, (in the strictly mechanical,
>random, evolutionary sense), nature doesn't need to make any species
>more long-lived IF it already rears enough kids to replace and
>multiply itself (careless millions of offspring in the case of
>insects, a handful in the case of careful humans).
Both strategies are successful, but neither one is more successful with
aging just "tacked on." Nature doensn't always do what's best (it doesn't
know), but it will do what ever small optimization is possible from a given
place. Aging happens only when there's a significant cost to prevent it.
>Some species (lobsters, orange roughy, rock fish) seem almost
>arbitrarily gifted with being long-lived, long-teleomered &
>non-senescent. And, also - (in the strictly purposeful, ordered,
>creationist sense) made delicious, to show that the Creator must have
>a gourmade sense of justice! :-)
All these species have few natural preditors (or can avoid those they have
easily), and live down in nice protected places. If it was *salmon* swimming
up little foot deep streams though guantlets of bears, that didn't age, THEN
I would use the word "arbitrarily." But there is nothing arbitrary about
this. There's a REASON we don't know exactly how long lobsters and rockfish
live-- even WE can't get at them easily.
>Most of the longer lived species have had extra eons to adapt
>compared to us primate newbies. Instead, we got a rapidly developed
>brain that made for a cultural adaptation toward longevity . Early man
>died sooner not because of a lesser evolved "aging" effect. He died
>because he hadn't yet invented (or learn to value) better food
>storage, crop planning, varied diet, sanitation, and predator defense
>(both the saber-toothed kind and the more voracious microbes).
But a slower aging rate (which we have) helps even here. Humans in the worst
conditions, even in prison camps, still show a doubling of mortality every
seven years-- the same as in the best conditions. That's aging. It's what
makes 30 years die when 15 year olds survive, and 40 year olds die when 30
years olds survive.
>Nature had no time, nor reason, to endown man with longer telomers or
>an enhanced ALC/ALA metabolism. Us little buggers were already killing
>everything else, eating & reproducing well and using up resources.
No. Humans struggled for millions of years without even making it out of
East Africa.
>Ultimately, longevity will be understood as an engineering problem.
>ALC/ALA is just another early, flint tool pointing to the solution.
>"Natural" and chemical tools may give away to nanotech and waveform
>solutions. Entrophy is always inevitable, but aging's multiple causes
>will be treated just as someone maintains the many needs of a beloved
>antique car (even when it requires near total renovation or
>duplication of original
Agreed.
--
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.
parts).
Alex Brands
> Alex Brands wrote in message ...
> >On Fri, 22 Feb 2002, it was written:
> >> Snobs be gone!
> >>
> >> Once upon a time, our fellow lad
> >> rambled on about "Re: Aging and ALC/lipoic acid (was: alpha lipoic
> >> acid eliminates wrinkles?)."
> >> Our champion being bored in sci.med.nutrition retorts, thusly ...
> >>
> >> >> Sure, and aging obviously causes problems with that. If you stayed
> >> >> physiologically 20 forever, you could obviously raise a lot more
> children
> >> >> until the sabertooth or bad hunting season or placenta previa or
> whatever
> >> >> got you.
> >>
> >> You got it backwards.
> >>
> >> A long life is a disadvantage in Darwinian Evolution.
> >>
> >> The most successful life form on planet earth are the Insects. And,
> >> Insects have extremely short life spans. :-)
> >
> >Perhaps they are the most successful animal life form, but they don't come
> >close to bacteria. Of course, bacteria have an even shorter generation
> >time.
>
> But they don't really age.
That's why I used the phrase "generation time" rather than "life span"
like John.
Also, I would amend my statement about insects. I believe nematodes are
more successful than insects in many ways.
Joann Evans
>
> x-no-archive: yes
>
> Snobs be gone!
>
> Once upon a time, our fellow lad
> rambled on about "Re: Aging and ALC/lipoic acid (was: alpha lipoic
> acid eliminates wrinkles?)."
> Our champion being bored in sci.med.nutrition retorts, thusly ...
>
> >> physiologically 20 forever, you could obviously raise a lot more children
> >> until the sabertooth or bad hunting season or placenta previa or whatever
> >> got you.
>
>
> A long life is a disadvantage in Darwinian Evolution.
>
> The most successful life form on planet earth are the Insects. And,
> Insects have extremely short life spans. :-)
>
What we 'geeks' know is the difference between a trait being an
advantage, and it merely *not* being a *dis*advantage.
If the (potentially) longer-lived individuals have no reproductive
advantage over the shorter-lived ones in their particular ecological
niche, the long-life trait tends to disappear.
If you happen to have a physiology that would permit you to live to
500, but the individuals in your species are highly likely to be dead of
various causes after age 50, then you have no advantage over someone
whose genes would probably have let him get to 100.
Indeed, if he/she has better self-repair mechanisms at the expense of
longevity, then he/she has a distinct avantage.
As long as you last long enough to reproduce (and in the case of
larger animals, espically humans where brain development continues
*after* birth, due to physical limitations in the size of the offspring
a human female can deliver), and rase offspring to the point of
self-survival, no trait that increases your longevity much beyond that,
will be selected for.
Insects do well (if you consider their total individual numbers
'success'...if so, what about bacteria?) because they can reproduce in
large numbers (certainly compared to humans) and don't need to be
'raised' after birth, so it matters little if they're optomized to live
hard and fast. Big mammals can't do that, so greater longevity is an
advantage, to a point of diminishing returns. After that, it just
doesn't matter. A sabertooth, or an infection from a cut, probably got
you anyway....
Thomas Carter
"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message news:<a58rrs$3u9$1...@slb7.atl.mindspring.net>...
> >"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
> news:<a50oui$nc5$1...@nntp9.atl.mindspring.net>...
> >> "lad" <ch...@my-deja.com> wrote in message
> >> news:1e1efc6b.02022...@posting.google.com...
> >> > If you could slow aging this easily, why doesn't your body do it?
> >> > > Evolution has no reason to want you to age more rapidly when you
> could
> be
> >> > > (at a small synthetic cost) age more slowly.
> >> >
> >Hi,
> >That is clearly the conventional wisdom, and I almost always bet on
> >the favorite. In health matters I bet her to show when possible. But
> >the fickle nag frequently loses. (at the track and in medical science)
> >There are many possible reasons why evolution might want us dead
> >early. IE, Grand, or Greatgrandmother might be a breeding ground for
> >microbes that selectively take out her progeny.
>
> That's ridiculous. If you've ever had kids you know how much more likely it
> is to be the other way around.
Yes, That is because the grandmother has acquired immunity to many
common infectious diseases. But these are not the group-fatal ones.
When the new, plague type microbes come she is just as likely or more
so to catch and incubate them as the kids. In fact more so with her
weakened immune system. While she is incubating these serious diseases
she is likely to provide them an opportunity to mutate Thus in effect
creating on occasion the group, or progeny killing disease. The case
can also be made more simply. Grand/greatgrandmothers
increase population density. Which increases risk of plague.
>In any case, it relies on a kin selection
> argument, and these are never good when they rely on having a weak kin
> selection advantage (or disadvantage) overpowering a direct disadvantage to
> the breeding of the individual
Would you mind providing some evidence for this argument? One that
justifies the use of "never and weak" in the face of historical fact
like the bubonic plauge and the genocide of the Carribean Indians by
Spanish presence.
> (which aging always is). Any increased risk
> you have to dying in pregancy or childbirth after 18 is due to aging. If
> nature could take care of this easily, it would.
Yes this is a fine point. But I think that nature has done a fine job
of starting serious aging after the child birth years. In fact it was
this rather steep increase in the degeneration of the body after about
30-40 good years that first made me wonder if it were not posible that
nature was trying to kill me on purpose. That and of course the fact
that she lets my germ line stay young.
I claimed that many reasons exist that nature might want us
oldsters dead. But gave only one example. Far from the best in fact.
Do you think that there are none? Note that it only takes one to
validate my premise.
Thomas
David Wright
John 'the Man' <DeMan[05]@hotmail.com> wrote:
>
>Snobs be gone!
>
>Once upon a time, our fellow MattLB
> rambled on about "Re: Aging and ALC/lipoic acid (was: alpha lipoic
>acid eliminates wrinkles?)."
>Our champion being bored in sci.med.nutrition retorts, thusly ...
>
>>> You got it backwards.
>
>>> A long life is a disadvantage in Darwinian Evolution.
>
>>> The most successful life form on planet earth are the Insects.
>
>>Bacteria are the most successful form of life on the planet. By a long way.
>>MattLB
>
>A long life is a disadvantage in Darwinian Evolution.
Good to see that your knowledge of evolution is on the same dismal
plane as your knowledge in other areas.
-- David Wright :: alphabeta at prodigy.net
These are my opinions only, but they're almost always correct.
"If I have not seen as far as others, it is because giants
were standing on my shoulders."
Hua Kul
> teens (probably after a parentally arranged pairing). We'd have
> grandkids in our thirties. Then we would all check-out in our forties,
> if we're lucky.
>
> regarding sanitation, antibiotics and canned food. Now, for our next
> trick, we have to get busy jiggling all those cells and genes.
>
only thing proven to increase any mammal's maximum lifespan was CR,
and that was probably practiced much more widely in ancient
populations than it is today, although unintentionally (no fast food
joints in the jungle). How was the aging profile of ancient humans so
different from ours that they would have the diseases of aging in
their 40's? Written history is only 6k-7k years old, so we would have
no record of lifespan in populations older than that. If anything,
people who didn't die of acute causes should have been healthier than
us in old age due to greater amounts of CLA and omega-3 in their diets
and much less use of grain oils. It seems logical that people who did
make it to old age in the pre-industrialised world were healthier than
modern man and had at least the same maximum lifespan.
Peter H. Proctor
>From: g...@adres.nl (Hua Kul)
>Subject: Re: Aging and ALC/lipoic acid (was: alpha lipoic acid eliminates
>wrinkles?)
>Date: 25 Feb 2002 02:21:37 -0800
>>
>Science may have lengthened mankind's mean lifespan, but I thought the
>only thing proven to increase any mammal's maximum lifespan was CR,
PBN will to it too, some.
Dr P
Aubrey de Grey
Martin Banschbach wrote:
> Mitochondria produce superoxide free radicals. Everytime electrons
> move to oxygen in mitochondira this happens. There is an estimate of
> how much is formed in each mitochondria each day and how much of this
> gets out but that info is not stored in my memory banks or in my class
> notes.
Most people say 1% to 4% of the electrons going into the respiratory
chain end up in superoxide, but that's probably a big overestimate --
it was derived using very non-physiological conditions.
> All superoxide is produced by Coenzyme Q10. If you increase Q10 you
> increase superoxide production. Mitochondrial DNA codes for superoxide
> dismutase and this manganese requiring enzyme takes out most of the
> superoxide formed.
Ouch. Superoxide production at Complex III is indeed generally agreed
to be generated by one-electron oxidation of ubisemiquinone, but at
Complex I it seems to be upstream of the Q-binding site, probably at
iron sulphur centre N2 (see Lenaz's recent paper in FEBS Lett 505:364).
Also, mitochondrial superoxide dismutase is nuclear-coded.
> Breast cancer and prostate cancer cells lack mitochondrial superoxide
> dismutase (gene mutation took it out) and giving these cancer cells
> Q10 kills them in vitro.
I know of several reports that mitochondrial SOD expression is low in
many cancers, but I haven't seen any reports of mutations being found.
Also, I don't know that Q10 in vitro work you mention. Could you give
a reference please?
> Since our immune system also forms superoxide the total body load is
> probably pretty high. I have seen estimates of the amount of each free
> radical species that humans produce each day and I know that superoxide
> is near the top but I think nitric oxide is first (don't quote me on
> that).
Quote me on it instead :-) We make hugely more NO than O2-.
> Both exercise and Q10 supplementation appear to induce more formation
> of mitochondrial superoxide dismutase
Again, this is the first I've heard of either result. Could you give
references?
Aubrey de Grey
Martin Banschbach
> > All superoxide is produced by Coenzyme Q10. If you increase Q10 you
> > increase superoxide production. Mitochondrial DNA codes for superoxide
> > dismutase and this manganese requiring enzyme takes out most of the
> > superoxide formed.
>
> Ouch. Superoxide production at Complex III is indeed generally agreed
> to be generated by one-electron oxidation of ubisemiquinone, but at
> Complex I it seems to be upstream of the Q-binding site, probably at
> iron sulphur centre N2 (see Lenaz's recent paper in FEBS Lett 505:364).
> Also, mitochondrial superoxide dismutase is nuclear-coded.
Yea, I saw this paper when I was getting the references you wanted.
Our
biochemistry textbook and most still being published say the
superoxide
comes from Q10. If it's really coming from an iron-sulfur complex,
that's fine with me.
> > Breast cancer and prostate cancer cells lack mitochondrial superoxide
> > dismutase (gene mutation took it out) and giving these cancer cells
> > Q10 kills them in vitro.
>
> I know of several reports that mitochondrial SOD expression is low in
> many cancers, but I haven't seen any reports of mutations being found.
> Also, I don't know that Q10 in vitro work you mention. Could you give
> a reference please?
Biochem J 2002 Mar1;362(Pt2):401-412. There are several cancer cell
lines where
the promoter region for human MnSOD has been mutated to decrease
formation of MnSOD and prevent it's induction. This isn't the first
paper to show this, I only went back as far as I had to to try to
indicate that what I said was correct.
I have seen at least one paper where Q10 was added to culture media
where cancer cell apotosis occured. I gave up trying to find it.
There were many papers where Q10 addition alters the cell line (moves
it back to a more differentiated cell). I have spent a very large
amount of time in the past looking at Q10 and I'm pretty sure that
what I said is correct. But if it was only 1 paper, it's kind of like
finding a needle in a hay stack. Many different antioxidants can
induce apotosis in cultured cancer cells. Q10 would not be unique in
doing this. I could speculate about why antioxidants do this but it
would only be a guess. I would have to spend quite a bit of time
going over the published literature to make a firm analysis. I think
that p53 has something to do with it (getting it expressed again).
> > Since our immune system also forms superoxide the total body load is
> > probably pretty high. I have seen estimates of the amount of each free
> > radical species that humans produce each day and I know that superoxide
> > is near the top but I think nitric oxide is first (don't quote me on
> > that).
>
> Quote me on it instead :-) We make hugely more NO than O2-.
That's what I thought but did not want to state is as a fact.
> > Both exercise and Q10 supplementation appear to induce more formation
> > of mitochondrial superoxide dismutase
>
> Again, this is the first I've heard of either result. Could you give
> references?
>
> Aubrey de Grey
Aubrey,
There have been numerous studies where exercise was used in
both lab animals and humans to look at antioxidant enzyme induction.
Granted, most looked at zinc/copper SOD but I know I read at least
one paper where it was MnSOD in humans. If I had gone back, I
probably could have found it. Hyperbaric oxygen does some thing and
is very similiar to what vigorous exercise does.
Eur. J. Appl Physiol 2001 Nov;86(1):24-27. In rat skeletal muscle,
MnSOD activity increased 241% after exposure of the rats to hyperbaric
oxygen.
It appears that you are working on Q10. In my trip into medline I
learned something that I did not know before. Q10 may act as a
shuttle to move
electrons from NADH in the cytoplasm into the electron transport chain
in the mitochondria. It also appears to move into many different
membrane systems
just like E does when Q10 is used as a supplement. I guess I should
say that these actions are a hypothesis to explain some of the actions
of Q10 supplementation. It makes sense to me. What's your take?
"Coenzyme Q versus hypertension:does CoQ decrease endothelial
superoxide generation?" Med. Hypothesis 1999 Oct;53(4):300-304.
Aubrey de Grey
Martin Banschbach wrote:
> Biochem J 2002 Mar1;362(Pt2):401-412
Ah yes, and refs therein. Many thanks.
> I have seen at least one paper where Q10 was added to culture media
> where cancer cell apotosis occured. I gave up trying to find it.
> There were many papers where Q10 addition alters the cell line (moves
> it back to a more differentiated cell).
Ah, right -- but this is very different. I think what's happening in
situations like this is that the Q10 is acting as an antioxidant, i.e.
*reducing* the free radical load in the cell, and thereby giving the
cell a better chance to respond to its tumorous state by apoptosing,
differentiating, anything to avoid dividing. This is just as you say:
> Many different antioxidants can
> induce apotosis in cultured cancer cells. Q10 would not be unique in
> doing this. ... I think
> that p53 has something to do with it (getting it expressed again).
but in contrast to your original statement that "If you increase Q10
you increase superoxide production", which is what I found surprising.
> There have been numerous studies where exercise was used in both lab
> animals and humans to look at antioxidant enzyme induction. ...
> Hyperbaric oxygen does some thing and is very similiar to what vigorous
> exercise does.
>
> Eur. J. Appl Physiol 2001 Nov;86(1):24-27. In rat skeletal muscle,
> MnSOD activity increased 241% after exposure of the rats to hyperbaric
> oxygen.
Hyperbaric oxygen, sure -- but I would dispute that vigorous exercise
is very similar. The lack of a large increase in superoxide production
during exercise is well-documented -- it even has a name, "the exercise
paradox". It makes sense, too -- superoxide production is highest when
mitochondria are inactive, i.e. maintaining a high proton gradient due
to low ADP availability, which is just the opposite of what exercise
does.
> Q10 may act as a shuttle to move
> electrons from NADH in the cytoplasm into the electron transport chain
> in the mitochondria.
Sure -- via the glycerophosphate shuttle. There was some talk some
time back of it also using the cytochrome b5 system, but I don't think
that held up.
> It also appears to move into many different membrane systems
> just like E does when Q10 is used as a supplement. I guess I should
> say that these actions are a hypothesis to explain some of the actions
> of Q10 supplementation. It makes sense to me. What's your take?
> "Coenzyme Q versus hypertension:does CoQ decrease endothelial
> superoxide generation?" Med. Hypothesis 1999 Oct;53(4):300-304.
I rather doubt it. Cytosolic NADH is reoxidised perfectly well by the
malate/aspartate shuttle anyway. However, plasma membrane CoQ levels
may affect the rate of superoxide production more directly: CoQ is a
key component of the plasma membrane redox system, which makes plenty
of superoxide in certain circumstances.
Aubrey de Grey
Martin Banschbach
> is very similar. The lack of a large increase in superoxide production
> during exercise is well-documented -- it even has a name, "the exercise
> paradox". It makes sense, too -- superoxide production is highest when
> mitochondria are inactive, i.e. maintaining a high proton gradient due
> to low ADP availability, which is just the opposite of what exercise
> does.
Exercise is going to increase MnSOD activity. The following paper
is for MnSOD in rat heart muscle.
Am J Physiol Hear Circ Physiol 2001 Sep;281(3):H1346-1352.
The next paper looked at human coronary artery endothelial cells
in culture. If you go back through the literature you are going to
find that exercise increases MnSOD in both heart and skeletal muscle.
This paper attempted to find out why. They say that part of the
induction is coming from epinephrine.
Free Radic Biol Med 2001 Jan 15;30(2):148-153.
michaelprice
> "diana thorley" <dith...@aol.com> wrote in message
> news:3c728faf...@news.CIS.DFN.DE...
>
> > Also, on the radio and TV today there have been reports of of a study
> > in the USA which proved that a combination of L-carnitine and lipoic
> > acid reversed the ageing process.
>
> COMMENT:
> They proved no such thing. For all we know, these mice may die at the
> same age, but leave good-looking corpses. I once did a similar study with
> CoQ10, which was very confusing. Aging is fundamental and is not going
> to be greatly changed by two little nutrients (both of which your body can
> already make). If you could slow aging this easily, why doesn't your body
> do it?
But the evolutionary logic that says that no endogenously metabolised
substance (such as CoQ10, ALC and ALA) should significantly extend
maximum life span applies equally strongly to mean life span - and we
know that mean life spans are extendable with a range of endogenously
metabolised substances.
So the evolutionary argument against the anti-aging benefit of supplying
endogenous nutrients must be false.
> Evolution has no reason to want you to age more rapidly when you could be
> (at a small synthetic cost) age more slowly.
Perhaps the cost of metabolising some substances is higher than we realise.
Cheers,
Michael C Price
Tim Tyler
: If you could slow aging this easily, why doesn't your body do it?
:> Evolution has no reason to want you to age more rapidly when you could be
:> (at a small synthetic cost) age more slowly.
: I'm no Steven J. Gould :-), but the conventional wisdom has always
: been that nature/evolution doesn't care a rat's rectum about how long
: you live. Just as long as you can crank out and successfully rear
: enough offspring.
It cares about how long you are fertile for - and even how long you
live after that while you're providing parental care - but certaintly
the net output of offspring is the overriding factor:
Living a long life is of no use to the evolutionary process if do do it by
living in a cave and spending your time in prayer.
The question is what the synthetic cost of producing the ALA and ALC is.
If large enough, evolution may indeed have favoured the short
burn over any long-term benefits - and thus individuals who want to live
for extended periods (and have resources to spend on doing so) might
benefit from supplementation.
--
__________
|im |yler Index of my domains: http://timtyler.org/ t...@iname.com
Tim Tyler
:> If we truly "lived in nature" then we'd all be moms n' dads in our
:> teens (probably after a parentally arranged pairing). We'd have
:> grandkids in our thirties. Then we would all check-out in our forties,
:> if we're lucky.
: People checked out in their 40's BECAUSE of aging. [...]
Probably less than today. In the past, fewer will have died of old
age, and more will have died through predation and accidents -
factors that increase the probability of death of the all members of
the population.
:> Having the wisdom and support of gramps or great-grand-mom may help
:> the provision/procreation network, but it doesn't seem necessary.
: No, but it's helpful. And besides, this is "group-selection." [...]
If the grandparents stay with the family, the force can be localised
so that it applies preferentially to the grandchildrn - in
which case invoking group selection is not necessary.
: If humans could remain youthful (i.e., reproductive longer) by
: producing a little more lipoic acid and acyl carnitine, they'd
: surely have evolved to do it.
Yes - but it depends on *how* much longer, *how* much the synthesis
costs metabolically, and the availability of the precursors in foods.
Actyl-Carnitine is certainly not cheap to buy.
Tim Tyler
: "Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
:> Aging is fundamental and is not going
:> to be greatly changed by two little nutrients (both of which your body can
:> already make). If you could slow aging this easily, why doesn't your body
:> do it?
: But the evolutionary logic that says that no endogenously metabolised
: substance (such as CoQ10, ALC and ALA) should significantly extend
: maximum life span applies equally strongly to mean life span - and we
: know that mean life spans are extendable with a range of endogenously
: metabolised substances.
: So the evolutionary argument against the anti-aging benefit of supplying
: endogenous nutrients must be false.
The argument - when correctly phrased - does not assert that
no endogenously metabolised substance should significantly
extend maximum life span.
It /should/ assert that no *inexpensive volumes* of endogenously
metabolised substance whose precursors are *commonly available* should
significantly extend maximum life span without *reducing fertility* in
the interim.
Tim
(Yamamura T.,Antioxid Redox Signal.2001 Feb,3(1)103-12).
Tim
Lawrence Foard
>The argument - when correctly phrased - does not assert that
>no endogenously metabolised substance should significantly
>extend maximum life span.
>
>It /should/ assert that no *inexpensive volumes* of endogenously
>metabolised substance whose precursors are *commonly available* should
>significantly extend maximum life span without *reducing fertility* in
>the interim.
The life extension arguments contain an assumption which is incorrect, that
is that no supplement is worth while unless it extends life. What if a
supplement improves life without extending life span? I'd rather even have a
supplement shorten life slightly if it meant a healthy life.
--
Be a counter terrorist perpetrate random senseless acts of kindness
Rave: Immanentization of the Eschaton in a Temporary Autonomous Zone.
I'm looking for computer hardware donations for charities, E-mail me.
Available for contracting http://www.farviolet.com/~entropy/resume.txt
Steve Harris
>"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
>news:a4un2i$8e4$1...@slb6.atl.mindspring.net...
>> "diana thorley" <dith...@aol.com> wrote in message
>> news:3c728faf...@news.CIS.DFN.DE...
>>
>> > Also, on the radio and TV today there have been reports of of a study
>> > in the USA which proved that a combination of L-carnitine and lipoic
>> > acid reversed the ageing process.
>>
>> COMMENT:
>> They proved no such thing. For all we know, these mice may die at the
>> same age, but leave good-looking corpses. I once did a similar study with
>> CoQ10, which was very confusing. Aging is fundamental and is not going
>> to be greatly changed by two little nutrients (both of which your body
can
>> already make). If you could slow aging this easily, why doesn't your body
>> do it?
>
>But the evolutionary logic that says that no endogenously metabolised
>substance (such as CoQ10, ALC and ALA) should significantly extend
>maximum life span applies equally strongly to mean life span - and we
>know that mean life spans are extendable with a range of endogenously
>metabolised substances.
Not really, for extension of mean life span by curve-squaring is often the
sort of thing that modern medicine does-- it saves people from drying of
diseases in middle age, and gets them into geriatric-land. But evolution
doesn't care about that. If there was some chemical which kept you from
getting a tumor at 55 and delayed it to age 75 if you had a lot more, would
your body make that stuff for you in quantity? Likely not.
>So the evolutionary argument against the anti-aging benefit of supplying
>endogenous nutrients must be false.
Nope.
michaelprice
> michaelprice wrote in message ...
> >"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
>>news:a4un2i$8e4$1...@slb6.atl.mindspring.net...
>>> "diana thorley" <dith...@aol.com> wrote in message
>>> news:3c728faf...@news.CIS.DFN.DE...
>>>
>>> > Also, on the radio and TV today there have been reports of of a study
>>> > in the USA which proved that a combination of L-carnitine and lipoic
>>> > acid reversed the ageing process.
>>>
>>> COMMENT:
>>> They proved no such thing. For all we know, these mice may die at the
>>> same age, but leave good-looking corpses. I once did a similar study
>>> with CoQ10, which was very confusing. Aging is fundamental and is
>>> not going to be greatly changed by two little nutrients (both of which
>>> your body can already make). If you could slow aging this easily, why
>>> doesn't your body do it?
>>
>> But the evolutionary logic that says that no endogenously metabolised
>> substance (such as CoQ10, ALC and ALA) should significantly extend
> >maximum life span applies equally strongly to mean life span - and we
>> know that mean life spans are extendable with a range of endogenously
>> metabolised substances.
>
>
> Not really, for extension of mean life span by curve-squaring is often the
> diseases in middle age, and gets them into geriatric-land. But evolution
> doesn't care about that. If there was some chemical which kept you from
> getting a tumor at 55 and delayed it to age 75 if you had a lot more,
> would your body make that stuff for you in quantity?
It would if you were still capable of reproducing or conferring benefit
on your descendants/ relatives. I thought it was a common observation with
a range of curve-squaring regimes that the animals seem youthful (e.g.
more activity, darker coats, better maze running ability) up to just prior
to turning belly-up. Isn't that what you observed with your own
CoQ10 experiments? And what the ALA and ALCar experiments reported?
(Okay the latter did not test for curve-squaring, I know, since they appear
to have sacrificed the subjects. But good candidates for mean LE.)
And there are a number of other nutrients that have extended mean
LS - is there any late-life reproductive fitness data available?)
Presumably their reproductive fitness is similarly enhanced.
> Likely not.
>
>
>> So the evolutionary argument against the anti-aging benefit of supplying
>> endogenous nutrients must be false.
>
> Nope.
Yup.
Cheers,
Michael C Price
Aubrey de Grey
Martin Banschbach wrote:
> Exercise is going to increase MnSOD activity. The following paper
> is for MnSOD in rat heart muscle.
>
> Am J Physiol Hear Circ Physiol 2001 Sep;281(3):H1346-1352.
Thank you for finding this article; however I would be reluctant to
read too much into it. The exercise training regimen would have
caused a rise in mitochondrial content, which necessarily raises all
mitochondrial protein content and enzyme activity when measured per
unit mass of total protein (which is what was done).
> If you go back through the literature you are going to
> find that exercise increases MnSOD in both heart and skeletal muscle.
As I say, I'm not aware of any report of such a response per unit
mitochondrial protein, as opposed to total protein.
Aubrey de Grey
Tim
only paper I am aware of on the issue I would suspect it may be
universally applicable. Exercise would most certainly increase
activation of TrxR due to the high vulnerability of sulfur containing
proteins to oxidative damage and this could be in part the reason
sulfur-containing antioxidants like ALA and NAC, as well as selenium
to increase resistance to induced oxidative stress rather than just by
the more widely suggested increase in glutathione and glutathione
peroxidase. Much research has been done of late, particularly in the
last year or so on the Thioredoxin system as research on redox
signaling will undoubtedly tell us a lot about aging in general. Some
brief references on the issue.
Am J Respir Cell Mol Biol 1997 Dec;17(6)713-26
Elevation of manganese superoxide dismutase gene expression by
thioredoxin.
Das KC et al
Am J Clin Nutr 2000 Aug 72(2 Suppl)65S-69S
Thiol homeostasis and supplements in physical exercise.
Sen CK, Packer L
Am J Physiol Cell Physiol 2001 Mar, 280(3)C621-7
McCardle A et al
Tim
Max Watt
> Thioredoxin increases MnSOD expression in E. coli. Though this is the
> only paper I am aware of on the issue I would suspect it may be
> universally applicable. Exercise would most certainly increase
> activation of TrxR due to the high vulnerability of sulfur containing
> proteins to oxidative damage and this could be in part the reason
> sulfur-containing antioxidants like ALA and NAC, as well as selenium
> to increase resistance to induced oxidative stress rather than just by
> the more widely suggested increase in glutathione and glutathione
> peroxidase. Much research has been done of late, particularly in the
> last year or so on the Thioredoxin system as research on redox
> signaling will undoubtedly tell us a lot about aging in general. Some
So does epinephrine. Is this increased expression or an increase in
the number of mitochondria???
Free Radic Biol Med 2001 Jan 15;30(2):148-53 Related Articles, Books,
LinkOut
Epinephrine upregulates superoxide dismutase in human coronary artery
endothelial cells.
Mehta JL, Li D.
Department of Medicine, University of Florida College of Medicine and
VA Medical Center, Gainesville, FL, USA. Meh...@UAMS.edu
Regular exercise resulting in release of catecholamines is an oxidant
stress, and yet it protects humans from acute cardiac events. We
designed this study to examine the effect of epinephrine on free
radical release and endogenous superoxide dismutase (SOD) gene and
protein expression in human coronary artery endothelial cells
(HCAECs). HCAECs were incubated with epinephrine (10(-9) to 10(-5) M)
alone or with the water-soluble analog of vitamin E (trolox) (10(-5)
M), the lipid-soluble vitamin E (5 x 10(-5) M), or the
beta(1)-adrenergic blocker atenolol (10(-5) M). At 1 and 24 h of
incubation with epinephrine, superoxide anion generation increased by
102 and 81% in the HCAECs. There was a marked increase in both MnSOD
and Cu/ZnSOD mRNA and protein, as determined by RT-PCR and Western
Analysis, respectively. Both MnSOD and Cu/ZnSOD activities were also
increased. Pretreatment of HCAECs with trolox and vitamin E decreased
superoxide anion generation (p <.05 vs. epinephrine alone) and blocked
the subsequent upregulation of SOD mRNA and protein. Treatment of
cells with the beta-blocker atenolol also blocked the upregulation of
SOD (p <.05 vs. epinephrine alone). These observations suggest that
epinephrine via beta(1)-adrenoceptor activation causes superoxide
anion generation, and the superoxide subsequently upregulates the
endogenous antioxidant species SOD. These observations may be the
basis of long-term benefits of exercise.
PMID: 11163531 [PubMed - indexed for MEDLINE]
Tim
increased production of free radicals. In the case of thioredoxin this
may be the mechanism that mediates or senses the increase and induces
the response by upregulating MnSOD. The Thioredoxins are a family of
proteins with cytoprotective properties to oxidative stress, so an
increase in MnSOD expression would be consistent with that.
Thioredoxin reductase (TrxR) is a selenium containing enzyme that
regenerates oxidized thioredoxin(s). The way a cell responds to
oxidative damage probably has a lot to do with cellular aging.
At least from the abstract you cite as to whether its due to an
increase in mitochondria can't be discerned.
Tim
gary
Multi-oil for their complexions. MaryKay sales people use four to eight
grams of the oils daily as their not-so-secret weapon.
-gary
"mbansch314" <mbans...@cox.net> wrote in message
news:mskc8.5742$Ap6.3...@news2.east.cox.net...
> > wife wants to buy this stuff to look younger...any comments??/
>
> I doubt if lipoic acid is going to eliminate skin wrinkles. Omega-3 fatty
> acids may work though.
>
>
DB
I wonder if 4-8 grams is enough. A tablespoon of flax oil weighs around 14
grams. Just make sure it is properly preserved. It is much more susceptable
to peroxidation than normal oils.
Steve Harris
>I wonder if 4-8 grams is enough. A tablespoon of flax oil weighs around 14
>grams. Just make sure it is properly preserved. It is much more susceptable
>to peroxidation than normal oils.
Yep. I have this picture of people applying enough flax oil (paint thinner)
to their faces to give themselves a permanent lacquer-job, and come out
looking like Goldie Hawn and Meril Streep in _Death Becomes Her_.
This free-radical driven cross-linking and oxidation reaction in linseed oil
is what drives the "drying" of oil based paints (and what starts spontaneous
fires in thinner-soaked rags). It's a very interesting reaction, as the
polymer finish which is left is very tough and impermiant. One of the few
things that mummies have in common besides being jerked by a lot of
salt-packing, is in being lacquered by linseed oil painting afterwards.
The only stuff I know of that oxidizes and polymerizes in this way faster
than alpha linolenic acid, is docosahexaenoic acid, (DHA) the major lipid
in brains. If you ever wondered at why the Eskimos tanned and preserved
hides by pounding brains into the raw skin sides, now you know. It's
basically a super lacquer, and it dries into a polymer which keeps oxygen
out in much the same way as for painted walls and mummies. Same mechanism.
Steve
Uncle Al
>
> DB wrote in message ...
>
> >I wonder if 4-8 grams is enough. A tablespoon of flax oil weighs around 14
> >grams. Just make sure it is properly preserved. It is much more susceptable
> >to peroxidation than normal oils.
>
> Yep. I have this picture of people applying enough flax oil (paint thinner)
> to their faces to give themselves a permanent lacquer-job, and come out
> looking like Goldie Hawn and Meril Streep in _Death Becomes Her_.
>
> This free-radical driven cross-linking and oxidation reaction in linseed oil
> is what drives the "drying" of oil based paints (and what starts spontaneous
> fires in thinner-soaked rags). It's a very interesting reaction, as the
> polymer finish which is left is very tough and impermiant. One of the few
> things that mummies have in common besides being jerked by a lot of
> salt-packing, is in being lacquered by linseed oil painting afterwards.
>
> The only stuff I know of that oxidizes and polymerizes in this way faster
> than alpha linolenic acid, is docosahexaenoic acid, (DHA) the major lipid
> in brains. If you ever wondered at why the Eskimos tanned and preserved
> hides by pounding brains into the raw skin sides, now you know. It's
> basically a super lacquer, and it dries into a polymer which keeps oxygen
> out in much the same way as for painted walls and mummies. Same mechanism.
Native wisdom: Every animal has the brains to tan its own hide. One
wonders about incidence of kuru and Kreutzfeld-Jacob syndrome amongst
the natives.
Take your 500 mg of Vitamin C, 400 IU of Vitamin E, and a multivitamin
after dinner (asssuming no idiosyncratic medical anomalies or
pathologies). Be careful you do not purchase any bottle sporting the
word "natural."
--
Uncle Al
http://www.mazepath.com/uncleal/
(Toxic URL! Unsafe for children and most mammals)
"Quis custodiet ipsos custodes?" The Net!
ada
major addition: Decreasing estrogen also plays a role. Estrogen
decreasing starts within 10 years of being fully menopausal (a period
that is called perimenopause), or as a result of hysterectomy, or
losing too much weight to either losing menses or experiencing
irregularity on periods.
I have been on ERT (estrogen replacement therapy) for almost 10 years
now. If I forget to stick my patch for several hours, two things
happen: my skin getting wrinkly and worst, I suffer from lower back
pain that spreads to my legs' joints has. The second has to do with
the fact that low estrogen tightens ligaments (no, the pain has
nothing to do with reduced bone density; my two weeks old DEXA placed
me slightly over one standard deviation above the average of my age
group). All those "natural" phytoestrogens, or other pharmaceuticals
that only relieve hot flashes and bone thinning don't help my
ligaments and wrinkly skin mainly because they only partly replace
estrogen.
Hereditary is also a big player.
regards,
ada
Mark Thorson
> Take your 500 mg of Vitamin C, 400 IU of Vitamin E, and a multivitamin
> after dinner (asssuming no idiosyncratic medical anomalies or
> pathologies). Be careful you do not purchase any bottle sporting the
> word "natural."
But Al, don't you remember telling us how dangerous fumed silica
is? That "silicon dioxide" listed as an ingredient _is_ fumed silica.
It's used as a glidant, for making the powders flow through the
tabletting or encapsulation equipment more easily.
Also, some people have trouble sleeping if they take their
vitamins in the evening instead of the morning. It seems to
make the brain more "busy".
DB
...
> Also, some people have trouble sleeping if they take their
> vitamins in the evening instead of the morning. It seems to
> make the brain more "busy".
Yeah. That's the B-complex. Not sure which of them.
Uncle Al
You can eat fumed silica, you should not inhale it.
I earned some money as a student volunteering my brain for
electroencephalographic studies. I was uniformly paid off and told
not to return. An awful lot of you folks have horribly aberrant
wiring compared to baseline Uncle Al.
Happiness is hearing an encephalographer in the adjacent room say in
rising pitch and volume, "What the Hell..."
Ed McBride
> > Uncle Al wrote:
> >
> > > Take your 500 mg of Vitamin C, 400 IU of Vitamin E, and a multivitamin
> > > after dinner
Except my sister, a VERY good internal-medicine doc, suggests 800-1000 IU of
E and one aspirin, anywhere from the 81 mg dosage to the 325 mg standard
one.
Ed
Uncle Al
Oil-soluble vitamins are inefficiently excreted. OD on Vitamin E
leads to blood clotting disorders and visual impairment (competition
with Vitamin A). Aspirin causes gastric bleeding no matter how
administered, including IV.
Adherence to self-medication outside the envelope puts you at risk for
idiosyncratic reactions. RDA's are calculated two standard deviations
above deficiency disease onset in rats. Chronic megadosing is no more
clever than eating just enough to avoid deficiency disease. You want
your auto engine oil level to be topped off, not overfilled or
bottomed out.
DB
> Ed McBride wrote:
>>
>> > > Uncle Al wrote:
>> > >
>> > > > Take your 500 mg of Vitamin C, 400 IU of Vitamin E, and a
>> > > > multivitamin after dinner
>>
>> Except my sister, a VERY good internal-medicine doc, suggests 800-1000 IU
>> of E and one aspirin, anywhere from the 81 mg dosage to the 325 mg
>> standard one.
>> Ed
>
> Oil-soluble vitamins are inefficiently excreted. OD on Vitamin E
> leads to blood clotting disorders and visual impairment (competition
> with Vitamin A). Aspirin causes gastric bleeding no matter how
> administered, including IV.
Not at those dosages.
> Adherence to self-medication outside the envelope puts you at risk for
> idiosyncratic reactions. RDA's are calculated two standard deviations
> above deficiency disease onset in rats.
Guess they made a mistake. RDAs (now called DV's, by the way) are not
enough to prevent heart disease or birth defects or the plethora of free
radical-related illnesses.
Chronic megadosing is no more
> clever than eating just enough to avoid deficiency disease. You want
> your auto engine oil level to be topped off, not overfilled or
> bottomed out.
I feel pretty clever, though. Must be all the supplements.
Steve Harris
Uncle Al wrote:
> Ed McBride wrote:
>>
>> > > Uncle Al wrote:
>> > >
>> > > > Take your 500 mg of Vitamin C, 400 IU of Vitamin E, and a
>> > > > multivitamin after dinner
>>
>> Except my sister, a VERY good internal-medicine doc, suggests 800-1000 IU
>> of E and one aspirin, anywhere from the 81 mg dosage to the 325 mg
>> standard one.
>> Ed
>
> Oil-soluble vitamins are inefficiently excreted. OD on Vitamin E
> leads to blood clotting disorders and visual impairment (competition
> with Vitamin A). Aspirin causes gastric bleeding no matter how
> administered, including IV.
>Not at those dosages.
COMMENT
Yes, even that these dosages. It's the antiplatelet effect on GI ulcers
that you wouldn't ordinarily otherwise notice. In the Physician's Health
Study (PHS) where the aspirin dose was 325 mg every other day, they had
siginicantly more admissions to the hospital for GI bleed in the aspirin
group. So it's not a benign drug, even at only anti-platelet doses. I think
the good effects outweigh risks in many groups (all smokers, and probably
most men over 40 and women over 50), but you really need to know your blood
picture and family history and medical history to take a good guess at this.
We don't know for sure, because no study (not even the PHS, which was the
biggest) has looked at aspirin long enough to assess its effect on all-cause
mortality. The only drugs we know those answers for are the statins (they
do extend life in people with high LDLs, even if they've not had a previous
MI or known cardiovascular event). We don't know the life extending effect
(if any) for aspirin, nor vitamin C, nor vitamin E, nor niacin in the
general population, or even for high LDL people. We know precious little
about any of these last set of substances, even as secondary preventives.
So a bit of humility is in order. The statins are presently the best-tested
"life-extension drugs" known. We know far more about their long term health
effects that we do megadose vitamins. You may rightly complain about that,
but do it to your congressman. The science is as I've reported. The drug
companies have the 100's of millions to find stuff like this out, and no
vitamin C maker does.
>Chronic megadosing is no more
> clever than eating just enough to avoid deficiency disease. You want
> your auto engine oil level to be topped off, not overfilled or
> bottomed out.
>>I feel pretty clever, though. Must be all the supplements.
Nah, probably just narcissism. The cure is medline. Go thou and read.
SBH
Martin Banschbach PhD
> above deficiency disease onset in rats
Minor point, it's two standard deviations above the mean for human data, not
rat data.
--
Marty B. "You are what you eat."
http://centernet.okstate.edu/nutrition/index.html
The above website is for educational purposes
only. Material in this website and posted material
represents the opinion of Martin Banschbach,
Ph.D. and does not reflect Oklahoma State
University policy or position on nutrition.
Issues regarding the diagnosis and treatment
of human disease can not be addressed
by material in the above website or by
Martin Banschbach, Ph.D.
Any comments made by Martin
Banschbach, Ph.D. are invalid unless
confirmed by your personal physician.
allana
wrote:
>
>> > Uncle Al wrote:
>> >
>> > > Take your 500 mg of Vitamin C, 400 IU of Vitamin E, and a multivitamin
>> > > after dinner
>
if you are taking vitamin e..why are you taking aspirin..vit e is just
as good, with no side effects..vit e should be less than 1gram ( 800
iu ) is about max .( take 400 iu 2 times daily)
MUGSYŠ
wrote:
>> Except my sister, a VERY good internal-medicine doc, suggests 800-1000 IU of
>> E and one aspirin, anywhere from the 81 mg dosage to the 325 mg standard
>> one.
>> Ed
>
>Oil-soluble vitamins are inefficiently excreted. OD on Vitamin E
>leads to blood clotting disorders and visual impairment (competition
>with Vitamin A).
This brings up a point that you never see Vit E past 400 UI on the
shelves.
Thanks for that bit of data re: competing with A...
mcgill.
DB
Actually there are 800, 1000, and 1500 IU softgels available on some store
shelves. I take around 1000 IU natural E and 200 mg gamma E. Generally
speaking, the more supplements one takes the better, imo. Call it a hunch
based on a shitload of animal data.
DB
But the data needs to be balanced with theory and common sense.
> So a bit of humility is in order. The statins are presently the
> best-tested "life-extension drugs" known. We know far more about their
> long term health effects that we do megadose vitamins. You may rightly
> complain about that,
> but do it to your congressman. The science is as I've reported. The drug
> companies have the 100's of millions to find stuff like this out, and no
> vitamin C maker does.
I stand corrected.
>
>>Chronic megadosing is no more
>> clever than eating just enough to avoid deficiency disease. You want
>> your auto engine oil level to be topped off, not overfilled or
>> bottomed out.
>
>>>I feel pretty clever, though. Must be all the supplements.
>
>
> Nah, probably just narcissism. The cure is medline. Go thou and read.
>
> SBH
Yes sir.
Steve Harris
Actually there are 800, 1000, and 1500 IU softgels available on some store
shelves. I take around 1000 IU natural E and 200 mg gamma E. Generally
speaking, the more supplements one takes the better, imo. Call it a hunch
based on a shitload of animal data.
COMMENT:
What animal data is that? Decades of trying to get animals to live longer
by supplementing them with vitamins has generally been a total failure. They
don't live as long at 1/2 RDA, but it's very hard to see difference between
RDA and 2x RDA (or RDI or whatever the current obfuspeak is these days).
Poor Tappel has done those vitamin E/life span studies several times.
Results: nada. All these things protect well against certain free-radical
damage in lab assays. How that translates to real life isn't clear. And
what the dose needed isn't clear.
Steve Harris
Uncle Al wrote in message <3C88E535...@hate.spam.net>...
>Oil-soluble vitamins are inefficiently excreted. OD on Vitamin E
>leads to blood clotting disorders and visual impairment (competition
>with Vitamin A).
Nah. There's been large studies of E at doses of 1600 IU a day (the
Alzheimer's prevention studies) for several years. Nobody had problems with
clotting or vision. This is a theoretical problem but only in people who are
very marginal in vitamin K status, and in practice that takes Coumadin.
Even then you can compensate for vitamin E taking, so long as the patient
doesn't change routine.
Vitamin E is oil soluble but doesn't behave like it in excretion. If you
take a lot, the excess is rapidly converted to water soluble metabolites
which are conjugated with gluconate by the liver, and excreted in the urine.
SBH
Laura S
>speaking, the more supplements one takes the better, imo. Call it a hunch
Now that is really scary.
Laura of NC
If you can't be a good example, then you'll just have to be a horrible warning.
-Catherine Aird-
Thomas Carter
DB <wire...@pacbell.net> wrote in message news:<0Zmi8.1338$td3.93...@newssvr14.news.prodigy.com>...
> Steve Harris wrote:
>
> > So a bit of humility is in order. The statins are presently the
> > best-tested "life-extension drugs" known. We know far more about their
> > long term health effects that we do megadose vitamins. You may rightly
> > complain about that,
> > but do it to your congressman. The science is as I've reported. The drug
> > companies have the 100's of millions to find stuff like this out, and no
> > vitamin C maker does.
>
Yes, they are quite well tested. The 30-35% end point reductions
generally work out to about a two year life extension, and this is in
cohorts pre-selected to be the most effected. In a population of
healthy baby boomers the benefits would probably be measured in
months. One gram capsules of fish oil give about the same benefit.
One oz. of nuts 4-6 times a week appear to extend life span by four
to seven years. Moderate and high levels of Vit. C vs. less than 60mg
appear to do about the same for men. And a combination of C and E
appear to do slightly better. High vs. moderate levels have hardly
been studied at all.
The largest maker of vit. C is Roche who is also one of the biggest
drug companies. Here is a study they commissioned.
The health effects of vitamin C supplementation: a review.:
J Am Coll Nutr: 14:2:124-36 (1995)
THIS STUDY WAS SPONSORED BY ROCHE. MANUFACTURER OF C
A comprehensive review of the literature indicates that populations
with long-term consumption of higher than RDA levels of vitamin C (>
or = 60 mg/day) from foods and/or supplements have reduced risks of
cancer at several sites, cardiovascular disease, and cataracts. The
safety of higher than RDA intakes of vitamin C is confirmed in eight
placebo- controlled, double-blind studies and six non-placebo clinical
trials in which up to 10,000 mg of vitamin C was consumed daily for up
to 3 years. There are no clinical data which suggest that vitamin C's
enhancement of non-heme iron absorption in individuals with low iron
status could be a critical factor in the possible increased risk of
heterozygous hemochromatosis-related cardiovascular disease. In fact,
the cumulative data do not confirm that iron status is related to risk
of cardiovascular disease. Moreover, higher than RDA intakes of
vitamin C have been associated with several indices of lowered
cardiovascular disease risk including increases in HDL, and decreases
in LDL oxidation, blood pressure and cardiovascular mortality PMID:
7790686
The benefit/risk ratio of these interventions is strongly positive
IMO. With the recent Statin problems that have surfaced the prevailing
opinion among health professionals is that they are only indicated for
heart patients with high choelesterol.
Thomas
Steve Harris
Thomas Carter wrote in message ...
>
>Yes, [statins] are quite well tested. The 30-35% end point reductions
>generally work out to about a two year life extension, and this is in
>cohorts pre-selected to be the most effected.
I'd like to see your math on that. The total impact of cardiovascular
disease on the general population is a life span loss of around 12 years.
This includes stroke, but statins help there also. This is an average over
everyone, so it's surely higher than this for people with risk factors. If
you can cut it by 1/3rd, you're going to do considerably better than 2
years.
> In a population of
>healthy baby boomers the benefits would probably be measured in
>months.
Disagree.
>One gram capsules of fish oil give about the same benefit.
>One oz. of nuts 4-6 times a week appear to extend life span by four
>to seven years.
Sorry, but this is not from prospective data, and is suspect. There's
probably something quite different about the kinds of people who eat a lot
of nuts. Like they're Seventh-Day Adeventists, and who knows what else they
do.
Yes, eat nuts. I'm reasonably sure they're good for you. But the quality of
the evidence is not so good as it is for statins.
>Moderate and high levels of Vit. C vs. less than 60mg
>appear to do about the same for men.
Men who drink. You get a 30% drop in mortality if you don't have the very
lowest vitamin C levels. Big deal. And again, it's retrospective.
DB
Normal rats, yes. They live an ideal life. Good diet, moderate exercise,
low-stress, no viral infections, no sunlight or drugs or pollution. But
I've seen alot of abstracts where massive doses of certain nutrients
prevented damage from toxins, carcinogens, UV exposure, hypoxia, etc.
If I drowned or had a stroke or something I might be protected by my high
intake of lipoic acid and other antioxidants.Most people don't take very
good care of their health. Loading up on antioxidants could save their
lives. Ideally, no one would need to take supplements. But this is the real
world.
--
Neuroprotection by the metabolic antioxidant alpha-lipoic acid.
Packer L, Tritschler HJ, Wessel K.
Department of Molecular and Cell Biology, University of California,
Berkeley 94720-3200, USA.
Reactive oxygen species are thought to be involved in a number of types of
acute and chronic pathologic conditions in the brain and neural tissue. The
metabolic antioxidant alpha-lipoate (thioctic acid, 1,
2-dithiolane-3-pentanoic acid; 1, 2-dithiolane-3 valeric acid; and 6,
8-dithiooctanoic acid) is a low molecular weight substance that is absorbed
from the diet and crosses the blood-brain barrier. alpha-Lipoate is taken
up and reduced in cells and tissues to dihydrolipoate, which is also
exported to the extracellular medium; hence, protection is afforded to both
intracellular and extracellular environments. Both alpha-lipoate and
especially dihydrolipoate have been shown to be potent antioxidants, to
regenerate through redox cycling other antioxidants like vitamin C and
vitamin E, and to raise intracellular glutathione levels. Thus, it would
seem an ideal substance in the treatment of oxidative brain and neural
disorders involving free radical processes. Examination of current research
reveals protective effects of these compounds in cerebral
ischemia-reperfusion, excitotoxic amino acid brain injury, mitochondrial
dysfunction, diabetes and diabetic neuropathy, inborn errors of metabolism,
and other causes of acute or chronic damage to brain or neural tissue. Very
few neuropharmacological intervention strategies are currently available
for the treatment of stroke and numerous other brain disorders involving
free radical injury. We propose that the various metabolic antioxidant
properties of alpha-lipoate relate to its possible therapeutic roles in a
variety of brain and neuronal tissue pathologies: thiols are central to
antioxidant defense in brain and other tissues. The most important thiol
antioxidant, glutathione, cannot be directly administered, whereas
alpha-lipoic acid can. In vitro, animal, and preliminary human studies
indicate that alpha-lipoate may be effective in numerous neurodegenerative
disorders.
--
Are you speaking of maximum lifespan? I'm not too concerned about that. 120
years is long enough. I just want to die healthy.
DB
> Vitamin E is oil soluble but doesn't behave like it in excretion. If you
> take a lot, the excess is rapidly converted to water soluble metabolites
> which are conjugated with gluconate by the liver, and excreted in the
> urine.
Interesting. Above what amount of vitamin e is an 'excess.'?
Thomas Carter
"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message news:<a6e7ln$lrh$1...@slb3.atl.mindspring.net>...
> Thomas Carter wrote in message ...
> >
> >Yes, [statins] are quite well tested. The 30-35% end point reductions
> >generally work out to about a two year life extension, and this is in
> >cohorts pre-selected to be the most effected.
>
>
> I'd like to see your math on that.
It's quite simple. Between the ages of 35 and 75 the risk of death
doubles every seven years for the general population. Mortality
benefits for the statins are less than 25%. Seven times .25 is less
than two years. So the statin takers would have the mortality rate of
someone two years younger if they were in the general population. They
are actually heart patients whose risk of death doubles sooner than
every seven years, thus I was being generous in my estimations.
> The total impact of cardiovascular
> disease on the general population is a life span loss of around 12 years.
There is no data at all on that. I have seen speculations as low as
three years. Where did you get the speculation of 12 years?
> This includes stroke, but statins help there also. This is an average over
> everyone, so it's surely higher than this for people with risk factors. If
> you can cut it by 1/3rd, you're going to do considerably better than 2
> years.
>
I don't follow your reasoning at all. It is already known that the rr
for mortality is over .75, the same as a cohort of people two years
younger. Are you trying to calculate a known quantity?
> > In a population of
> >healthy baby boomers the benefits would probably be measured in
> >months.
>
>
> Disagree.
>
>
> >One gram capsules of fish oil give about the same benefit.
> >One oz. of nuts 4-6 times a week appear to extend life span by four
> >to seven years.
>
> Sorry, but this is not from prospective data, and is suspect.
Not at all. See PMID: 9310278 and several papers on the famous GISSI
study, both are gold standard, placebo controlled, clinical trials
showing benefits for fish oil of 30 to 50%. Also search Medline for
nuts AND clinical trial[pt]. You will get 30 hits.
There's
> probably something quite different about the kinds of people who eat a lot
> of nuts. Like they're Seventh-Day Adeventists, and who knows what else they
> do.
Doesn't matter, they were compared with other Seventh Day Adventists.
Similiar results were seen in huge studies of Iowa post menapausal
women, the Harvard Nurses' study and their Health Proffessional's
Study.
> Yes, eat nuts. I'm reasonably sure they're good for you. But the quality of
> the evidence is not so good as it is for statins.
>
There is no evidence at all for statins except in heart patients, and
very little for heart patients without high choelesterol.
>
> >Moderate and high levels of Vit. C vs. less than 60mg
> >appear to do about the same for men.
>
> Men who drink. You get a 30% drop in mortality if you don't have the very
> lowest vitamin C levels. Big deal. And again, it's retrospective.
>
> SBH
They were prospective, not retrospective studies and more like 40, not
30%, that's about five extra years of life. And yes it is a big deal.
But yes you have hit on one of the major objections to the
epidemioligic vitamin studies. They compared the highest or the rest
of the quintiles/quartiles with the lowest. The full text of the
papers shows the highest vs. the average, or the middle group to much
less spectacular. Every one likes to select their statistics.
Here is one of the most favorable studies.
Established Populations for Epidemiologic Studies of the Elderly
Losonczy KG; Harris TB; Havlik RJ
(96302127 NLM)
We examined vitamin E and vitamin C supplement use in relation to
mortality risk and whether vitamin C enhanced the effects of vitamin E
in 11,178 persons aged 67-105 y who participated in the Established
Populations for Epidemiologic Studies of the Elderly in 1984-1993.
Participants were asked to report all nonprescription drugs currently
used, including vitamin supplements. Persons were defined as users of
these supplements if they reported individual vitamin E and/or vitamin
C use, not part of a multivitamin. During the follow-up period there
were 3490 deaths. Use of vitamin E reduced the risk of all-cause
mortality [relative risk (RR) = 0.66; 95% CI: 0.53, 0.83] and risk of
coronary disease mortality (RR = 0.53; 95% CI: 0.34, 0.84). Use of
vitamin E at two points in time was also associated with reduced risk
of total mortality compared with that in persons who did not use any
vitamin supplements. Effects were strongest for coronary heart disease
mortality (RR = 0.37; 95% CI: 0.15, 0.90). The RR for cancer mortality
was 0.41 (95% CI: 0.15, 1.08). Simultaneous use of vitamins E and C
was associated with a lower risk of total mortality (RR = 0.58; 95%
CI: 0.42, 0.79) and coronary mortality (RR = 0.47; 95% CI: 0.25,
0.87). Adjustment for alcohol use, smoking history, aspirin use, and
medical conditions did not substantially alter these findings. These
findings are consistent with those for younger persons and suggest
protective effects of vitamin E supplements in the elderly.
And this is from the NHANES study.
. Men who consumed at least 300 mg of ascorbic acid suffered 41
percent fewer deaths during that period compared with men who took
only 50 mg, in their food. They lived on the average 6 years longer.
All together over a million people have been investigated in about a
dozen studies, and not a single one has come out negetive.
Thomas
Steve Harris
Apparently anything over a few 10's of mg a day. But again, remember that
for the d-alpha tocopherol (but not the gamma or delta) you need to saturate
your body's alpha tocopherol binding protein stores before you start
excreting the extra quantitatively. If you start taking 400 IU a day it
takes a couple of weeks before you're excreting that much a day. For the
gamma or delta vitamers, the balance between ingestion and excretion happens
much more rapidly.
SBH
--
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Steve Harris
news:a7b55247.02030...@posting.google.com...
> Hi Steve,
>
> "Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
news:<a6e7ln$lrh$1...@slb3.atl.mindspring.net>...
> > Thomas Carter wrote in message ...
> > >
> > >Yes, [statins] are quite well tested. The 30-35% end point reductions
> > >generally work out to about a two year life extension, and this is in
> > >cohorts pre-selected to be the most effected.
> >
> >
> > I'd like to see your math on that.
>
> It's quite simple. Between the ages of 35 and 75 the risk of death
> doubles every seven years for the general population. Mortality
> benefits for the statins are less than 25%. Seven times .25 is less
> than two years. So the statin takers would have the mortality rate of
> someone two years younger if they were in the general population. They
> are actually heart patients whose risk of death doubles sooner than
> every seven years, thus I was being generous in my estimations.
If you risk doubles every 7 years, how much older do you have to be for your
risk to go up by 1.25?
1.25 = 2^(n/7)
so n = 7 * (ln 1.25) / (ln 2) = 2.25 years.
As for your assumption that the doubling time will be smaller for this group
than others, it's probably not warrented. People with coronary disease age
at the same rate as you and I; their mortality doubling time is the same.
It's that factor out front of the exponent (the "initial vulnerability
factor") that's different. For example in Japan the mortality doubling time
is the same as here-- the 7 years extra life span in Japan show up as an
all-cause age adjusted mortality only 50% of what ours is.
However, for given diseases, without life table analysis you really cannot
straightforwardly convert % mortality figures directly into years of life
gained or lost. You have to know something about the disease. Example,
suppose there were some dread disease which kills all children who have it,
between the ages of 1 and 2. A pill is developed which cures 25% of these
kids, allowing them a normal life span. If you give it at year 1, it
decreases mortality in the treatment group by 25%, over the next year. But
after that you can't calculate the effect because there's no demoninator.
And the average years of life gained are certainly more than 2.25, even
allowing for the aging process.
> > The total impact of cardiovascular
> > disease on the general population is a life span loss of around 12
years.
>
> There is no data at all on that. I have seen speculations as low as
> three years. Where did you get the speculation of 12 years?
That's from the 1993 Olshansky paper which doesn't have an abstract. I am
having a hard time finding this figure in abstact form-- give me a bit of
time.
> > >One gram capsules of fish oil give about the same benefit.
> > >One oz. of nuts 4-6 times a week appear to extend life span by four
> > >to seven years.
> >
> > Sorry, but this is not from prospective data, and is suspect.
>
> Not at all. See PMID: 9310278 and several papers on the famous GISSI
> study, both are gold standard, placebo controlled, clinical trials
> showing benefits for fish oil of 30 to 50%.
Which is only 4 to 7 years if you ignore your own argument about
subpopulations, note. Can't have it both ways <G>.
> There's
> > probably something quite different about the kinds of people who eat a
lot
> > of nuts. Like they're Seventh-Day Adeventists, and who knows what else
they
> > do.
>
> Doesn't matter, they were compared with other Seventh Day Adventists.
> Similiar results were seen in huge studies of Iowa post menapausal
> women, the Harvard Nurses' study and their Health Proffessional's
> Study.
It's still retrospective. Nobody has been randomized to nuts or placebo (And
how the heck would you do placebo anyway?). There's not even a prospective
open-label nuts or not study.
> > Yes, eat nuts. I'm reasonably sure they're good for you. But the
quality of
> > the evidence is not so good as it is for statins.
> >
> There is no evidence at all for statins except in heart patients, and
> very little for heart patients without high choelesterol.
That's not true. The largest statin study of all (see abstract below)
specifically excludes people with the highest cholesterols. Many of these
are merely high risk people, but not necessarily with proven disease. All
cause mortality was lowered by 12%, and there was no cholesterol theshhold
below which statins did no good. The antioxident vitamin supplmented
control group showed no benefits at all--- nyah, nyah. There's a
prospective vitamin trial, and vitamins did zip!
> > >Moderate and high levels of Vit. C vs. less than 60mg
> > >appear to do about the same for men.
> >
> > Men who drink. You get a 30% drop in mortality if you don't have the
very
> > lowest vitamin C levels. Big deal. And again, it's retrospective.
> >
> > SBH
>
> They were prospective, not retrospective studies and more like 40, not
> 30%, that's about five extra years of life.
Sorry, I want a reference for any prospective vitamin C trial that does what
you say.
> And yes it is a big deal.
It would be if it did what you say. But no such prospective trial of
vitamin C exists. As for the epidemiological studies, the kind of people who
take vitamins every day are a totally different group of people, socially,
mentally, psychologically, than people who don't. That shows up in morality
numbers, but it's very hard to prove it's the vitamins.
Anyway, here are some statin trials.
Int J Clin Pract 2002 Jan-Feb;56(1):53-6 Related Articles, Books, LinkOut
The MRC/BHF Heart Protection Study: preliminary results.
Collins R, Peto R, Armitage J.
Oxford Clinical Trials Service Unit.
The Heart Protection Study (HPS), with over 20,500 subjects, is the largest
trial of statin therapy ever conducted. It provides important and definitive
new information on women, the elderly, diabetics, and people with low
baseline cholesterol pre-treatment and those with prior occlusive
non-coronary vascular disease. It is a prospective double blind randomised
controlled trial with a 2 x 2 factorial design investigating prolonged use
(>5 years) of simvastatin 40 mg and a cocktail of antioxidant vitamins (650
mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene). The HPS
specifically included patients with high risk for coronary heart disease
(CHD) but characteristics that excluded them from participation in previous
statin trials. Simvastatin 40 mg treatment showed benefit across all patient
groups regardless of age, gender or baseline cholesterol value and proved
safe and well tolerated. Results show a 12% reduction in total mortality, a
17% reduction in vascular mortality, a 24% reduction in CHD events, a 27%
reduction in all strokes and a 16% reduction in non-coronary
revascularisations. Among high-risk patients in this western population
(with a minimum total cholesterol [TC] > or = 3.5 mmol/l at entry) there
appears to be no threshold cholesterol value below which statin therapy is
not associated with benefit; even among those with pre-treatment cholesterol
levels below current national recommended targets. Over the 5.5 year study
period patients and their doctors were encouraged to add an active non-study
statin to the study regimen if they wished to do so. Thus the trial
eventually had only two-thirds complying with the original
intention-to-treat design. Nevertheless, results were highly significant for
the study statin--simvastatin 40 mg once daily. Preliminary results of the
HPS are negative for the antioxidant vitamin cocktail but provide
reassurance that vitamins do no harm.
PMID: 11831837 [PubMed - in process]
Heh. Well, at least we have reassurance that vitamins do no harm <g>.
JAMA 1999 Dec 22-29;282(24):2340-6 Related Articles, Books, LinkOut
Comment in:
JAMA. 2000 Jun 14;283(22):2935-6.
JAMA. 2000 Jun 14;283(22):2935; discussion 2936.
Effect of statins on risk of coronary disease: a meta-analysis of randomized
controlled trials.
LaRosa JC, He J, Vupputuri S.
Office of the President, State University of New York Health Science Center
at Brooklyn, 11203, USA. jcla...@netmail.hscbklyn.edu
CONTEXT: Lowering low-density lipoprotein cholesterol (LDL-C) is known to
reduce risk of recurrent coronary heart disease in middle-aged men. However,
this effect has been uncertain in elderly people and women. OBJECTIVE: To
estimate the risk reduction of coronary heart disease and total mortality
associated with statin drug treatment, particularly in elderly individuals
and women. DATA SOURCES: Trials published in English-language journals were
retrieved by searching MEDLINE (1966-December 1998), bibliographies, and
authors' reference files. STUDY SELECTION: Studies in which participants
were randomized to statin or control treatment for at least 4 years and
clinical disease or death was the primary outcome were included in the
meta-analysis (5 of 182 initially identified). DATA EXTRACTION: Information
on sample size, study drug duration, type and dosage of statin drug,
participant characteristics at baseline, reduction in lipids during
intervention, and outcomes was abstracted independently by 2 authors (J.H.
and S.V.) using a standardized protocol. Disagreements were resolved by
consensus. DATA SYNTHESIS: Data from the 5 trials, with 30 817 participants,
were included in this meta-analysis. The mean duration of treatment was 5.4
years. Stati n drug treatment was associated with a20% reduction in total
cholesterol, 28% reduction in LDL-C, 13% reduction in triglycerides, and 5%
increase in high-density lipoprotein cholesterol. Overall, statin drug
treatment reduced risk 31 % in major coronary events (95% confidence
interval [CI], 26%-36%) and 21 % in all-cause mortality (95% CI, 14%-28%).
The risk reduction in major coronary events was similar between women (29%;
95% Cl, 13 %-42 %) and men (31 %; 95% CI, 26%-35%), and between persons aged
at least 65 years (32%; 95% CI, 23%-39%) and persons younger than 65 years
(31 %; 95% CI, 24%-36%). CONCLUSIONS: Our meta-analysis indicates that
reduction in LDL-C associated with statin drug treatment decreases the risk
of coronary heart disease and all-cause mortality. The risk reduction was
similar for men and women and for elderly and middle-aged persons.
Publication Types:
Meta-Analysis
PMID: 10612322 [PubMed - indexed for MEDLINE]
JAMA 1997 Jul 23-30;278(4):313-21 Related Articles, Books, LinkOut
Comment in:
JAMA. 1997 Nov 26;278(20):1660-1.
Cholesterol lowering with statin drugs, risk of stroke, and total mortality.
An overview of randomized trials.
Hebert PR, Gaziano JM, Chan KS, Hennekens CH.
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215-1204,
USA.
OBJECTIVE: To examine whether cholesterol lowering with
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin
drugs) reduces the risks of stroke and total mortality. DATA SOURCES: We
conducted a computerized literature search from 1985 through 1995 to
identify all published trials testing statin drugs. The Cholesterol and
Recurrent Events (CARE) data were added after the report was published in
October 1996. Our search was limited to English-language articles and
included published overviews containing relevant individual trials. TRIAL
SELECTION: Criteria for inclusion of randomized trials in the overview were
(1) statin drugs alone used to reduce lipid levels rather than
multifactorial interventions including another type of cholesterol-lowering
drug and (2) inclusion of data on deaths and/or strokes. DATA EXTRACTION:
Data were extracted by 2 researchers, and only minor discrepancies, which
were easily resolved by discussion, occurred. Principal investigators of the
trials and their funding agencies were also contacted to secure any relevant
data not included in the published reports. DATA SYNTHESIS: A total of 16
individual trials including approximately 29 000 subjects treated and
followed up an average of 3.3 years were included in the overview. The
average reductions in total and low-density lipoprotein cholesterol achieved
were large-22% and 30%, respectively. A total of 454 strokes (fatal plus
nonfatal) and 1175 deaths occurred. Those assigned to statin drugs
experienced significant reductions in risks of stroke of 29% (95% confidence
interval [CI], 14%-41%) as well as total mortality of 22% (95% CI, 12%-31%),
which was attributable to a significant reduction in cardiovascular disease
(CVD) deaths of 28% (95% CI, 16%-37%). There was no evidence of any
increased risk in non-CVD mortality (relative risk [RR], 0.93; 95% CI,
0.75-1.14). There was also no significant increase in risk of cancer (RR,
1.03; 95% CI, 0.90-1.17). CONCLUSION: This overview of all published
randomized trials of statin drugs demonstrates large reductions in
cholesterol and clear evidence of benefit on stroke and total mortality.
There was, as expected, a large and significant decrease in CVD mortality,
but there was no significant evidence for any increases in either non-CVD
deaths or cancer incidence.
Chris Allen
What does she mean by _E_?
-Chris
Steve Harris
news:698c89aa.02031...@posting.google.com...
Maybe she's a very mellow internist.
Well, probably not. E doesn't come in units. Maybe it should. Moon units,
say.
"I just, like totally, had 100 moon units of E. I'm so into, like totally,
never stopping this stuff. Awesome."
Tom Matthews
[snip]
> Int J Clin Pract 2002 Jan-Feb;56(1):53-6 Related Articles, Books, LinkOut
> The MRC/BHF Heart Protection Study: preliminary results.
> Collins R, Peto R, Armitage J.
> Oxford Clinical Trials Service Unit.
[snip]
> a cocktail of antioxidant vitamins (650
> mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene).
[snip]
> Preliminary results of the
> HPS are negative for the antioxidant vitamin cocktail but provide
> reassurance that vitamins do no harm.
> PMID: 11831837 [PubMed - in process]
>
> Heh. Well, at least we have reassurance that vitamins do no harm <g>.
No one with any brains should expect that these few vitamins alone would
make any significant difference. It is now well known that giving both
racemic alpha tocopherol and beta carotene without the other E vitamers
and carotenoids can even be harmful in some circumstances. The
antioxidant "network" is far too complex for these three alone to
simulate its potential benefits.
A well-designed complex supplement cocktail has not yet been tested for
mortality reduction in any mammal. Nor has such a cocktail in concert
with other health measures such as food choices, calorie restriction,
exercise, etc.
--Tom Matthews
MoreLife for us all - http://morelife.org
Reality based tools for More Life in quantity & quality
Chris Allen
> The largest statin study of all (see abstract below)
> specifically excludes people with the highest cholesterols. Many of these
> are merely high risk people, but not necessarily with proven disease. All
> cause mortality was lowered by 12%,
12% of the studied population became immortal after consuming statin drugs?
-Chris
Steve Harris
Bingo, you've put your finger on the problem if why you can't translate %
mortality reduction for a given small time frame into years of life gained
total, because to do that you need to know the shape of the mortality
curves. Obviously since nobody is immortal and 100% of people die, a %
reduction in gross mortality (deaths/year = dN/dt) in a population NOW from
mere curve-squaring must inevitably translate to a % INCREASE in that
population's mortality LATER. Still, one group can gain years of average
life from having its mortality risk go down early in life, only to go up
later in life. This would be the case with a drug which eliminated all heart
disease and stroke (say) but didn't do anything about cancer. At some point,
the age-adjusted total cancer death rate, but not the cancer fractional
mortality rate (ie, age-adjusted cancer risk per 1000 people) would be
higher in the group that was saved from cardiovascular disease-- simply
because there would be more of them to die of cancer if they didn't die of
heart disease. You gotta die of something.
If this isn't a curve squaring thing, and total fractional mortality is
somehow reduced in one group as compared to another, at ALL times (so the
fractional slope of population decline = 1/N * dN/dt in one group is at all
times less than in the other), there will come a time at which one group is
down to zero, and some of the other is alive, so the mortality *ratio*
between the two becomes unevaluatable. At that point, years of life lived
by members of the remaining group until they die of old age are all gravy,
and you can't tell how they impact the final averages until you know how
long their life span is going to be, as limited by other processes. This
kind of thing would happen with an antiaging drug that wasn't perfect-- say
one that slowed aging by 50%.
SBH
Max Watt
> Martin Banschbach wrote:
>
> > Exercise is going to increase MnSOD activity. The following paper
> > is for MnSOD in rat heart muscle.
> >
> > Am J Physiol Hear Circ Physiol 2001 Sep;281(3):H1346-1352.
>
> Thank you for finding this article; however I would be reluctant to
> read too much into it. The exercise training regimen would have
> caused a rise in mitochondrial content, which necessarily raises all
> mitochondrial protein content and enzyme activity when measured per
> unit mass of total protein (which is what was done).
>
> > If you go back through the literature you are going to
> > find that exercise increases MnSOD in both heart and skeletal muscle.
>
> As I say, I'm not aware of any report of such a response per unit
> mitochondrial protein, as opposed to total protein.
>
> Aubrey de Grey
I came across one that seems to show such an effect for a single acute
bout of exercise in rats, abstract below.
Whether cronic exercise would raise the rate of SOD production per
mitochondrion, is still and interesting, and open, question.
Incidently exercise also increase glutathion peroxidase activity,
which I suspect caloric restriction also does.
Max Watt
1: Pflugers Arch 2001 Jun;442(3):426-34
Superoxide dismutase gene expression is activated by a single bout of exercise
in rat skeletal muscle.
Hollander J, Fiebig R, Gore M, Ookawara T, Ohno H, Ji LL.
Department of Kinesiology and Interdisciplinary Nutritional Sciences, University
of Wisconsin-Madison, 53706, USA.
The goal of this experiment was to examine contraction-mediated activation of
superoxide dismutase (SOD) gene expression in rat superficial vastus lateralis
(SVL, type IIb) and deep vastus lateralis (DVL, type IIa) muscles. Female
Sprague-Dawley rats were randomly divided into exercise (E) and control (C)
groups that were sacrificed at 0, 1, 2, 4, 10, 24, and 48 h (n=6) following an
acute bout of treadmill exercise (25 m/min, 5% grade) to exhaustion (running
time approximately equals 1 h). Nuclear factor-kappaB (NF-kappaB) in DVL and SVL
showed maximal binding at 2 and 10 h respectively, and remained elevated.
Activator protein-1 (AP-1) showed maximal binding at 1 h post-exercise, and
returned to resting levels at 10 h in both muscles. Mn SOD mRNA abundance in the
DVL was increased at 0 (P<0.01), 1, and 2 h (P<0.05) post-exercise, whereas Mn
SOD protein was unchanged. In SVL, Mn SOD mRNA abundance was not altered by
exercise, whereas Mn SOD protein content was increased at 10 (P<0.05) and 24 h
(P<0.075) post-exercise. CuZn SOD mRNA was unchanged with exercise in DVL and
SVL, but CuZn SOD protein was elevated 48 h after exercise in both DVL and SVL
(P<0.01). Activities of Mn SOD, CuZn SOD and total SOD showed no change with
exercise in either muscle examined. These findings indicate that an acute bout
of exercise can increase binding of NF-kappaB and AP-1 in both SVL and DVL,
which may stimulate Mn SOD mRNA transcription in the more oxidative type DVL
muscle. The increased CuZn SOD protein contents seen post-exercise, without
increases in mRNA abundance in both DVL and SVL, suggest a translational
mechanism in this SOD isoform.
PMID: 11484775 [PubMed - indexed for MEDLINE]
maxwa...@yahoo.com (Max Watt) wrote in message news:<870a5d01.02031...@posting.google.com>...