Aging and ALC/lipoic acid (was: alpha lipoic acid eliminates wrinkles?)
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.
SBH
--
I welcome Email from strangers with the minimal cleverness to fix my address
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mark doran
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.
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.
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.
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
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.
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.
>
> 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.
>
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
Max Watt
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>...