Antioxidants vs. CR (was: MSRA extends life span...)
Chris Allen
http://groups.google.com/groups?hl=en&lr=&threadm=a7b55247.0203062121.b6d7222%40posting.google.com&rnum=1&prev=/groups%3Fhl%3Den%26lr%3D%26q%3Dmsra%26meta%3Dgroup%253Dsci.life-extension
> This is the gene we read about a few months ago that shortened life
> span in knock out mice.
http://groups.google.com/groups?hl=en&lr=&threadm=57475792.0110221554.79f9e78%40posting.google.com&rnum=2&prev=/groups%3Fhl%3Den%26lr%3D%26q%3Dmsra%26meta%3Dgroup%253Dsci.life-extension
Link to abstract of referenced journal paper:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11606777&dopt=Abstract
> Now we see that overexpression extends the
> life span if flies. the abstract is pretty sparse in info, but the
> free full text article will be available in a couple of months.
Done:
http://www.pnas.org/cgi/content/full/99/5/2748
These MSRA results indicate that CR is not the only way to increase
group lifespan. These animals were not calorie restricted:
<..snip..>
We found that the average body weight of the MSRA-overexpression male
animals was indistinguishable from that of either parental line at the
age of 10 days (0.6-0.7 mg per animal).
<..snip..>
Considering that the food intake in these animals is similar to that
of the control animals (Fig. 3B), the MSRA transgenic animals may be
more efficient metabolically.
<../snip..>
The results of this study indicate that antioxidant (AO) mediated life
extension (MSRA overexpression is one way of raising antioxidant
status {_paraquat killed only 10% of the male animals that
overexpressed MSRA in the nervous system (Fig. 3A). This finding
suggests that the lifespan extension is caused by the antioxidant
action of MSRA._}) avoids many undesirable side effects of CR mediated
life extension:
<..snip..>
Aging in many species is associated with a decline in physical
activity and also in reproductive vitality. We observed that the
transgenic flies overexpressing MSRA preferentially in the nervous
system or generally in the whole body were noticeably more active than
the control animals of the same age.
<..snip..>
at 50 days only a small number of pupae were produced in the control
groups, whereas in the MSRA-overexpression group the pupal production
was still at 75% of the peak value observed in much younger animals.
Because pupa production reflects multiple factors in reproduction,
such as mating frequency, egg laying, and egg hatching, the prolonged
pupa production period suggests that all the relevant steps in
reproduction are preserved by overexpression of MSRA.
<..snip..>
The peak copulation probability was greater and occurred faster in the
MSRA-overexpression animals
<..snip..>
Although the adult lifespan is extended by overexpression of MSRA, the
developmental time course up to the adult emergence was not altered
<..snip..>
the extended lifespan in these transgenic animals was achieved largely
by shifting the survival distribution to the right, suggesting that
the enzyme overexpression delays the onset of the same set of the
mortality factors that normally determine the lifespan in the control
groups.
<..snip..>
In summary, we have shown that overexpression of MSRA predominantly in
the Drosophila nervous system markedly extends lifespan. Unlike the
lifespan extension induced by some experimental manipulations, the
longer lifespan by MSRA overexpression is associated with many
desirable features. The MSRA transgenic flies retain normal food
intake and bodyweight, but they are more physically active. The MSRA
transgenic animals also maintain high physical and reproductive
activities much later into their lives than control animals. Some
Drosophila mutants show extended lifespans, but their body weights are
greater (45), potentially from fat accumulation. Many other mutations
that extend the lifespans of model organisms often lower their
physical activity and reproductive capacity. Mutant female
insulin-like receptor flies with abnormal endocrine function live
longer, but they are hypomorphic and sterile (54). Therefore, it may
be argued that overexpression of MSRA in Drosophila extends its
lifespan while maintaining quality of life. It will be of great
interest to see whether overexpression of MSRA extends lifespan in
mammals including humans.
<../snip..>
Median lifespans (days):
control MSRA overexpressed difference
male 45 80 +78%
female 58 95 +61%
-Chris
AO-LE. It simply works better.
Thomas Carter
Hi Chris,
Thanx for reminding me to update my info on this. The full text
is most interesting, especially the +78% for the hairy gender, which
is still most in need of life extending help. I have found that
apparently MSRA is active in humans, is less active with age, is
associated with a particular type of oxidative stress, and works to
maintain the all important calcium equilibrium in cells, whose loss is
associated with aging pathology. Unlike other antioxidants it is
active in repairing, rather than preventing oxidative damage. AND BEST
OF ALL IT IS POTENTIATED IN HUMANS BY ALPHA LIPOIC ACID. The pathway
can be seen in the following abstracts. ALA is a cofactor for PMSR
(MSRA), by reason of it being a (reducing equivalent)substrate needed
for reduction of methionine. Many proteins are repaired by reduction
of methionine by PMSR, in particular Alpha 1-P, and calmodulin which
are needed for healty lung function and cellular calcium equilibrium.
Thus it seems as if increased MSRA activity may be additive to the
functions of other antioxidant systems. Until something better comes
along I will increase my dosage of Ginkoe Biloba to be sure I don't
forget to take my ALA. :>)
Thomas
PS BTW I think your conclusion is shared by few. Mostly hungry people
trying to decide whether or not to break their diet again. :>)
Arzneimittelforschung 1998 Feb;48(2):144-8 Effects of dihydrolipoic
acid on peptide methionine sulfoxide reductase. Implications for
antioxidant drugs. Biewenga GP, Veening-Griffioen DH, Nicastia AJ,
Haenen GR, Bast A. Leiden/Amsterdam Center for Drug Research, Vrije
Universiteit, Department of Pharmacochemistry, The Netherlands. By
showing that dihydrolipoic acid (DHLA) reactivates oxidatively damaged
alpha-1 antiprotease (alpha 1-AP), a new antioxidant property of DHLA
is described. For the first time, it is shown that a drug is able to
reverse oxidative damage of physiologically essential macromolecules.
Until now, only antioxidant properties have been reported that prevent
oxidative stress. Repair of oxidized alpha 1-AP is catalysed by
peptide methionine sulfoxide reductase (PMSR, EC 1.8.4.6). It is found
that DHLA acts as a reducing cofactor for PMSR. Oxidized alpha 1-AP
has been implicated in the etiology of certain lung diseases.
Generally, by stimulating PMSR, DHLA may exert a curative effect in
diseases accompanied by oxidative stress. PMID:
9541724…………………..
 8. DHLA can provide peptide methionine sulfoxide reductase
with reducing equivalents. This enhances the repair of oxidatively
damaged proteins such as alpha-1 antiprotease. 9. Through the
lipoamide dehydrogenase-dependent reduction of lipoic acid, the cell
can draw on its NADH pool for antioxidant activity additionally to its
NADPH pool, which is usually consumed during oxidative stress. 10.
Within drug-related antioxidant pharmacology, lipoic acid is a model
compound that enhances understanding of the mode of action of
antioxidants in drug therapy.
PMID: 9378235 ………………………..
FEBS Lett 1996 Jan 22;379(1):74-6 Protection against
peroxynitrite-dependent tyrosine nitration and alpha 1-antiproteinase
inactivation by oxidized and reduced lipoic acid. Whiteman M,
Tritschler H, Halliwell B. Neurodegenerative Disease Research Centre,
King's College, London, UK. Peroxynitrite, formed by combination of
superoxide radical with nitric oxide, is a reactive tissue-damaging
species apparently involved in the pathology of several human
diseases. Peroxynitrite nitrates tyrosine residues and inactivates
alpha 1-antiproteinase. We show that both lipoic acid and
dihydrolipoic acid efficiently protect against damage by
peroxynitrite. By contrast, other disulphides tested did not. The
biological antioxidant effects of lipoate/dihydrolipoate may involve
scavenging of reactive nitrogen species as well as reactive oxygen
species. PMID: 8566234
……………………………………..
Arch Biochem Biophys 1994 Jul;312(1):114-20 Lipoic acid favors
thiolsulfinate formation after hypochlorous acid scavenging: a study
with lipoic acid derivatives. Biewenga G, de Jong J, Bast A.
Leiden/Amsterdam Center for Drug Research, Vrije Universiteit,
Department of Pharmacochemistry, The Netherlands. Lipoic acid, the
oxidized form of 6,8-dimercapto-octanoic acid has a strained cyclic
disulfide in a 1,2-dithiolane ring. Recently its antioxidant activity
gained attention. Hypochlorous acid (HOCl) is an oxidant produced by
neutrophils. A prominent effect of HOCl is the inactivation of
alpha-1-antiproteinase. Due to this inactivation, the ability of
alpha-1-antiproteinase to inhibit elastase is lost.
……………The 1,2-dithiolane ring may enhance
the reactivity toward HOCl compared to less strained disulfides,
resulting in the formation a thiolsulfinate. PMID:
8031117……………………..
MsrA and MsrB act on oxidized calmodulin, each by repairing four to
six of the eight methionine sulfoxide residues initially present, and
(iii) simultaneous action of both MsrA and MsrB allowed full reduction
of oxidized calmodulin. A possibility is that these two ubiquitous
methionine sulfoxide reductases exhibit different substrate
specificity. PMID: 11677230………………
Biochemistry 1999 Jan 5;38(1):105-12 Repair of oxidized calmodulin by
methionine sulfoxide reductase restores ability to activate the plasma
membrane Ca-ATPase. (calmodulin is a small calcium binding protein
that is necessary to maintain cellular calcium equilibrium. The
ability is lost with age as is the activity of Msr) Sun H, Gao J,
Ferrington DA, Biesiada H, Williams TD, Squier TC. Department of
Molecular Biosciences, Mass Spectrometry Laboratory, University of
Kansas, Lawrence 66045-2106, USA. We have investigated the ability of
methionine sulfoxide reductase (MsrA) to maintain optimal calmodulin
(CaM) function through the repair of oxidized methionines, which have
been shown to accumulate within CaM in senescent brain [Gao, J., Yin,
D. H., Yao, Y., Williams, T. D., and Squier, T. C. (1998) Biochemistry
37, 9536-9548]. Oxidatively modified calmodulin (CaMox) isolated from
senescent brain or obtained by in vitro oxidation was incubated with
MsrA. This treatment restores the functional ability of CaMox to
activate the plasma membrane (PM) Ca-ATPase, confirming that (i) the
decreased ability of CaM isolated from senescent animals to activate
the PM Ca-ATPase results solely from methionine sulfoxide formation
and (ii) MsrA can repair methionine sulfoxides within cytosolic
proteins. We have used electrospray ionization mass spectrometry to
investigate the extent and rates of methionine sulfoxide repair within
CaMox. Upon exhaustive repair by MsrA, there remains a distribution of
methionine sulfoxides within functionally reactivated CaMox, which
varies from three to eight methionine sulfoxides. The rates of repair
of methionine sulfoxides within individual tryptic fragments of CaMox
vary by a factor of 2, where methionine sulfoxides located within
hydrophobic sequences are repaired in preference to methionines that
are more solvent accessible within the native structure. However, no
single methionine sulfoxide is completely repaired in all CaM
oxiforms. Decreases in the alpha-helical content and a disruption of
the tertiary structure of CaM have previously been shown to result
from methionine oxidation. Repair of selected methionine sulfoxides in
CaMox by MsrA results in a partial refolding of the secondary
structure, suggesting that MsrA repairs methionine sulfoxides within
unfolded sequences until native-like structure and function are
re-attained. The ability of CaMox isolated from senescent brain to
fully activate the PM Ca-ATPase following repair by MsrA suggests the
specific activity of MsrA is insufficient to maintain CaM function in
aging brain. These results are discussed in terms of the possible
regulatory role MsrA may play in the modulation of CaM function and
calcium homeostasis under conditions of oxidative stress. PMID:
9890888 …………………………..
J Neurochem 1999 Oct;73(4):1660-6 Decrease in peptide methionine
sulfoxide reductase in Alzheimer's disease brain. Gabbita SP, Aksenov
MY, Lovell MA, Markesbery WR. Sanders-Brown Center on Aging,
University of Kentucky, Lexington 40536-0230, USA. Previous studies
have shown that the pathophysiology of Alzheimer's disease (AD) is
linked to oxidative stress. Oxidative damage to different biomolecular
components of the brain is a characteristic feature of AD. Recent
evidence suggests that methionine may act as an antioxidant defense
molecule in proteins by its ability to scavenge oxidants and, in the
process, undergo oxidation to form methionine sulfoxide. The enzyme
peptide, methionine sulfoxide reductase (MsrA), reverses methionine
sulfoxide back to methionine, which once again is able to scavenge
oxidants. The purpose of this study was to measure the activity of
MsrA in the brain of AD patients compared with control subjects. Our
results showed that there was a decline in MsrA activity in all brain
regions studied in AD and this decline reached statistical
significance in the superior and middle temporal gyri (p < 0.001),
inferior parietal lobule (p < 0.05), and the hippocampus (p < 0.05) in
AD. An elevation of protein carbonyl content was found in all brain
regions except the cerebellum in AD and reached statistical
significance in the superior and middle temporal gyri and hippocampus.
Messenger RNA analysis suggests that the loss in enzyme activity may
be the result of a posttranslational modification of MsrA or a defect
of translation resulting in inferior processing of the MsrA mRNA. Our
results suggest that a decline in MsrA activity could reduce the
antioxidant defenses and increase the oxidation of critical proteins
in neurons in the brain in AD. PMID: 10501213
Michael
cal...@efn.org (Chris Allen) wrote in message news:<698c89aa.02052...@posting.google.com>...
> On 2002-03-06, Thomas Carter wrote:
> http://groups.google.com/groups?hl=en&lr=&threadm=a7b55247.0203062121.b6d7222%40posting.google.com&rnum=1&prev=/groups%3Fhl%3Den%26lr%3D%26q%3Dmsra%26meta%3Dgroup%253Dsci.life-extension
> > Now we see that overexpression extends the
> > life span if flies. the abstract is pretty sparse in info, but the
> > free full text article will be available in a couple of months.
> Done:
> http://www.pnas.org/cgi/content/full/99/5/2748
>
> These MSRA results indicate that CR is not the only way to increase
> group lifespan.
No one is making so broad a claim. There are all KINDS of ways to
extend LS in flies. If you wanna get sophisticated, you can cause them
to overexpress SOD, or induce functional mutations in Indy. If you
wanna do a home science project, just keep the little buggers in your
'fridge. Easy -- & unsuccessful, in mammals.
The unique claim of CR is that it is (unfortunately) thus far the only
intervention which slows intrinsic aging (as operationally defined at
the population level as extended maximum SPECIES (not just strain or
colony) lifespan, & increased mortality doubling time) in MAMMALS (not
poikilotherms, whose aging can be slowed by turning down their
metabolism).
Until someone extends max LS of a mammalian species, the universe for
anti-aging interventions relevant to humans contains only (a) CR, (b)
speculative, make-the-case hypothesis-building, and (c) pie-in-the-sky
(of theological or speculative technological nature).
-Michael
Peter H. Proctor
>From: mik...@lycos.com (Michael)
>Subject: Re: Antioxidants vs. CR (was: MSRA extends life span...)
>Date: 27 May 2002 19:30:38 -0700
>The unique claim of CR is that it is (unfortunately) thus far the only
>intervention which slows intrinsic aging (as operationally defined at
>the population level as extended maximum SPECIES (not just strain or
>colony) lifespan, & increased mortality doubling time) in MAMMALS (not
>poikilotherms, whose aging can be slowed by turning down their
>metabolism).
PBN (phenylbutylnitrone ) can also increase max lifespan in rodents.
Dr P
lad
I think I read the r-lipoic.com site *suggesting* that r-alpha-lipoic
acid may extend max LS by mimicing the insulin sparing effects of CR.
Peter H. Proctor
>From: ch...@my-deja.com (lad)
>Subject: Re: Antioxidants vs. CR (was: MSRA extends life span...)
>ppro...@neosoft.com (Peter H. Proctor) wrote in message
>> PBN (phenylbutylnitrone ) can also increase max lifespan in rodents.
>>
>> Dr P
>I think I read the r-lipoic.com site *suggesting* that r-alpha-lipoic
>acid may extend max LS by mimicing the insulin sparing effects of CR.
Don't know about this one. Do they give an reference ?
Here is an abstract on PBN
Biosci Biotechnol Biochem 1998 Apr;62(4):792-4 Related Articles, Books, LinkOut
A spin trap, N-tert-butyl-alpha-phenylnitrone extends the life span of mice.
Saito K, Yoshioka H, Cutler RG.
Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
"To characterize the pharmacological effects of N-tert-butyl-alpha-phenyl
nitrone (PBN) on life span, we administered PBN in drinking water to 24.5
-month-old mice, and the survivors were counted. Their water consumption
and body weights were measured as biological markers. PBN-treated animals
as compared with control animals had prolonged mean and maximum life spans.
Their water consumption decreased but no significant change was found in their
body weights, indicating that the metabolism was improved. Results showed that
PBN indeed affects physiological functions and extends life span. We propose
that nitric oxide release from PBN may be involved in altering the aging
process."
Tom Matthews
> Biosci Biotechnol Biochem 1998 Apr;62(4):792-4 Related Articles, Books, LinkOut
> A spin trap, N-tert-butyl-alpha-phenylnitrone extends the life span of mice.
> Saito K, Yoshioka H, Cutler RG.
> Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
>
> "To characterize the pharmacological effects of N-tert-butyl-alpha-phenyl
> nitrone (PBN) on life span, we administered PBN in drinking water to 24.5
> -month-old mice, and the survivors were counted. Their water consumption
> and body weights were measured as biological markers. PBN-treated animals
> as compared with control animals had prolonged mean and maximum life spans.
> Their water consumption decreased but no significant change was found in their
> body weights, indicating that the metabolism was improved. Results showed that
> PBN indeed affects physiological functions and extends life span. We propose
> that nitric oxide release from PBN may be involved in altering the aging
> process."
I think that it is highly likely that N-tert-butyl-hydroxylamine NtBHA would also
have the same effects. Perhaps without the somewhat toxic benzaldehyde breakdown
product from PBN, it might even work better.
--Tom Matthews
MoreLife for the rational - http://morelife.org
Reality based tools for More Life in quantity & quality
Peter H. Proctor
>From: Tom Matthews <t...@morelife.org>
>Subject: Re: Antioxidants vs. CR (was: MSRA extends life span...)
>I think that it is highly likely that N-tert-butyl-hydroxylamine NtBHA would
>also have the same effects. Perhaps without the somewhat toxic benzaldehyde
>breakdown product from PBN, it might even work better.
Possibly. BTW, NtBHA formation connects the Nitrones ( such as PBN
) with the Nitroxide Spin labels such as TEMPOL, for which the hydroxylamines
are prodrugs.
Dr P
Michael
ppro...@neosoft.com (Peter H. Proctor) wrote in message news:<F8458EB2CD17EDC8.E740F2A2...@lp.airnews.net>...
> rodents [later in thread citing the mistitled "A spin trap,
> N-tert-butyl-alpha-phenylnitrone extends the life span of mice" (1)].
Dr. Proctor, as I've pointed out before, this paper doesn't
demonstrate any such thing. Looking at the Table 1, the max LS of
controls was 31.7 mo, vs. 33.3 mo
(or ~1012 days) in the PBN-treated mice.
This doesn't represent an increase in mouse max LS, which is right in
this ballpark: ~1100 days. & these were C57BL/6J mice: a long-lived
strain.
Some might argue that the small intercohort difference, & failure to
actually exceed SPECIES (or even STRAIN!) max LS, was due to having
started the animals on the stuff so late. In a true anti-aging therapy
(as CR is, in lab rodents), this would hold. But THE PAPER ANSWERS
THIS QUESTION -- in the negative.
"In this experiment, PBN administratin was started at 24.5 months, so
we changed it to 21.5 and 18.5 months to ascertain when the PBN the
[sic] effect begins. Although ... life spans were also prolonged
compared with the control, no significant difference was found on them
[sic] with those started at 24.5 months (data not shown). From this
result, it was considered that ... young animals ... have enough
capacity to protect themselves from [ROS], but [PBN] becomes effective
on the older ones because they lacked this capacity and as a result,
PBN acts as an anti-oxidant."
PBN repeatably FAILED to extend SPECIES max LS in these experiments.
Starting younger did not improve the effect.
These data do not, therefore, demonstrate that PBN slows aging. It
most likely shows that it helps rodents to survive the suboptimal
conditions in Saito et al's lab, which artificially shorten their LSs.
(This is the same problem with Pierpaoli's melatonin experiments (2):
the max LS of their ACTIVE group was <900 days, which is not only
shorter than the AL max LS in properly-cared-for rodents, but shorter
than the *AV'G* LS Weindruch & Walford's ADULT-ONSET CR B6s (3)). The
other "maximum LS increase" using PBN, in the painfully screwed up SAM
mouse, was even further away from meeting the target (4).
If your cohort is short-lived, making it longer-lived does not show
slowed aging. If you start with people with Down's syndrome, you don't
get to claim retarded aging just because the folks undergoing your
intervention live to be 70.
As Walford is fond of saying, "show me the 45-month old mouse."
-Michael
1: Saito K, Yoshioka H, Cutler RG.
A spin trap, N-tert-butyl-alpha-phenylnitrone extends the life span of
mice.
Biosci Biotechnol Biochem. 1998 Apr;62(4):792-4.
PMID: 9614711
2. Pierpaoli W, Dall'Ara A, Pedrinis E, Regelson W.
The pineal control of aging. The effects of melatonin and pineal
grafting on the
survival of older mice.
Ann N Y Acad Sci. 1991;621:291-313. No abstract available.
PMID: 1859093
3. Weindruch R, Walford RL.
Dietary restriction in mice beginning at 1 year of age: effect on
life-span and
spontaneous cancer incidence.
Science. 1982 Mar 12;215(4538):1415-8.
PMID: 7063854
4. Edamatsu R, Mori A, Packer L.
The spin-trap N-tert-alpha-phenyl-butylnitrone prolongs the life span
of the
senescence accelerated mouse.
Biochem Biophys Res Commun. 1995 Jun 26;211(3):847-9.
PMID: 7598714
--
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is real). http://www.climatechangesolutions.com (Real choices)
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http://www.janeholtzkay.com/AsphaltNation (Another car choice).
Peter H. Proctor
>From: mik...@lycos.com (Michael)
>Subject: Re: Antioxidants vs. CR (was: MSRA extends life span...)
>All:
>ppro...@neosoft.com (Peter H. Proctor) wrote in message
>
>> PBN (phenylbutylnitrone ) can also increase max lifespan in
>> rodents [later in thread citing the mistitled "A spin trap,
>> N-tert-butyl-alpha-phenylnitrone extends the life span of mice" (1)].
>Dr. Proctor, as I've pointed out before, this paper doesn't
>demonstrate any such thing. Looking at the Table 1, the max LS of
>controls was 31.7 mo, vs. 33.3 mo
>(or ~1012 days) in the PBN-treated mice.
>This doesn't represent an increase in mouse max LS, which is right in
>this ballpark: ~1100 days. & these were C57BL/6J mice: a long-lived
>strain.
It does relative to the controls. Not a lot, but not much else (
chemical at least ) comes close.
>Some might argue that the small intercohort difference, & failure to
>actually exceed SPECIES (or even STRAIN!) max LS, was due to having
>started the animals on the stuff so late. In a true anti-aging therapy
>(as CR is, in lab rodents), this would hold. But THE PAPER ANSWERS
>THIS QUESTION -- in the negative.
snip...
>PBN repeatably FAILED to extend SPECIES max LS in these experiments.
>Starting younger did not improve the effect.
Ya have to compare with the controls. Again, the effect is not a
large one ( a few weeks, tho this translates to a couple of years or so in
humans. ). So you can't really use historical controls. Which is not really
the usual practice anyway.
>These data do not, therefore, demonstrate that PBN slows aging.
Where did I say PBN "slows aging" ? What the data shows is that PBN
extends maximum lifespan relative to controls. This could be by any one of
several mechanisms, including blocking some radical-mediated degenerative
process ( the "small" model for free radicals and aging, which nobody really
questions )
>If your cohort is short-lived, making it longer-lived does not show
>slowed aging. If you start with people with Down's syndrome, you don't
>get to claim retarded aging just because the folks undergoing your
>intervention live to be 70.
Dammit, never said it does. BTW, I have been publishing papers on
the role of free radicals in degenerative diseases for over thirty years.
I definitely know the difference between effects on these and on aging per
se....
Dr P
GeoWCherry
--
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is real). http://www.climatechangesolutions.com (Real choices)
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It's the way to go!
michaelprice
> The unique claim of CR is that it is (unfortunately) thus far the only
> intervention which slows intrinsic aging (as operationally defined at
> the population level as extended maximum SPECIES (not just strain or
> colony) lifespan, & increased mortality doubling time) in MAMMALS
Chromium picolinate has reportedly extended a mammalian species
maximum by 15% (see last ref)
[1] Composition and Biological Activity of Chromium-Pyridine Carboxylate
Complexes by GW Evans and DJ Pouchnik, Journal of Inorganic Biochemistry 49,
pg 177-187 (1993). This describes the action of dietary chromium picolinate
(relative to chromium chloride and chromium nicotinate) in reducing
glycation & plasma glucose levels in rats as they aged. (submitted March
1992 for publication.)
[2] Life span is increased in rats supplemented with a chromium-pyridine 2
carboxylate complex by Evans GW, Meyer LK in Adv Sci Res. 1994; 1:19-23.
[3] Chromium picolinate increases longevity by Evans GW, Meyer LK in Age
1992; 15: 134. The median lifespan increase from the above experiment was
reported at the 22nd American Aging Association conference (Oct 1992)
[4] Chromium Picolinate by GW Evans, (1996) ISBN 0895299119.
[5] The Longevity Factor: Chromium Picolinate by RA Passwater, ISBN
0879836199 (1993). Gives additional information about the
Evans-Meyer-Pouchnik chromium picolinate experiment on rats: Cohort maximum
lifespan extended by 17%, from 41 months to 48 months, extending the
previous species maximum by 15%. Number of rats involved, 30, 10 in each
group.
Cheers,
Michael C Price
GeoWCherry
> intervention which slows intrinsic aging (as operationally defined at
> the population level as extended maximum SPECIES (not just strain or
> colony) lifespan, & increased mortality doubling time) in MAMMALS
Michael Price:
Chromium picolinate has reportedly extended a mammalian species
maximum by 15% (see last ref)
<snipped references>
George Cherry:
For whatever it's worth???
Effect of chromium supplementation and exercise on body composition, resting
metabolic rate and selected biochemical parameters in moderately obese women
following an exercise program.
Volpe SL, Huang HW, Larpadisorn K, Lesser II.
Department of Nutrition, University of Massachusetts, Amherst 01003, USA.
vo...@nutrition.umass.edu
OBJECTIVE: To investigate the effect of chromium picolinate (CP)
supplementation on body composition, resting metabolic rate (RMR), selected
biochemical parameters and iron and zinc status in moderately obese women
participating in a 12-week exercise program. METHODS: Forty-four women, 27 to
51 years of age, were randomly assigned to two groups based on their body mass
index. Subjects received either 400 microg/day of chromium as a CP supplement
or a placebo in double-blind fashion and participated in a supervised
weight-training and walking program two days per week for 12 weeks. Body
composition and RMR were measured at baseline, 6 and 12 weeks. Selected
biochemical parameters and iron and zinc status were measured at baseline and
12 weeks. RESULTS: Body composition and RMR were not significantly changed by
CP supplementation. No significant differences in fasting plasma glucose, serum
insulin, plasma glucagon, serum C-peptide and serum lipid concentrations or in
iron and zinc indices were found between the two groups over time. Serum total
cholesterol concentration significantly decreased (p = 0.0016) over time for
all subjects combined, probably as a result of the exercise training. Exercise
training significantly reduced total iron binding capacity (TIBC) by 3% for all
subjects combined (p = 0.001 1). CONCLUSIONS: Twelve weeks of 400 microg/day of
chromium as a CP supplement did not significantly affect body composition, RMR,
plasma glucose, serum insulin, plasma glucagon, serum C-peptide and serum lipid
concentrations or iron and zinc indices in moderately obese women placed on an
exercise program. The changes in serum total cholesterol levels and TIBC were a
result of the exercise program.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 11506057 [PubMed - indexed for MEDLINE]
Michael
"michaelprice" <michae...@ntlworld.com> wrote in message news:<jvZJ8.27885$wd3.4...@news6-win.server.ntlworld.com>...
> > The unique claim of CR is that it is (unfortunately) thus far the only
> > intervention which slows intrinsic aging (as operationally defined at
> > the population level as extended maximum SPECIES (not just strain or
> > colony) lifespan, & increased mortality doubling time) in MAMMALS
>
> Chromium picolinate has reportedly extended a mammalian species
> maximum by 15% (see last ref)
... which is not peer-review (nor is (4)). By contrast, none of (1-3)
assert a max LS increase. If Evans had legit data showing a 15%
increase in species max LS, he'd have his choice of publication
venues. The claim is plainly both bunk & irrelevant to the human
situation, as we've discussed before:
... and following discussion.
-Michael
>
> [1] Composition and Biological Activity of Chromium-Pyridine Carboxylate
> Complexes by GW Evans and DJ Pouchnik, Journal of Inorganic Biochemistry 49,
> pg 177-187 (1993).
>
michaelprice
"Michael" <mik...@lycos.com> wrote in message
news:69779556.02060...@posting.google.com...
> All:
>
> "michaelprice" <michae...@ntlworld.com> wrote in message
news:<jvZJ8.27885$wd3.4...@news6-win.server.ntlworld.com>...
> > > The unique claim of CR is that it is (unfortunately) thus far the only
> > > intervention which slows intrinsic aging (as operationally defined at
> > > the population level as extended maximum SPECIES (not just strain or
> > > colony) lifespan, & increased mortality doubling time) in MAMMALS
> >
> > Chromium picolinate has reportedly extended a mammalian species
> > maximum by 15% (see last ref)
>
> ... which is not peer-review (nor is (4)). By contrast, none of (1-3)
> assert a max LS increase. If Evans had legit data showing a 15%
> increase in species max LS, he'd have his choice of publication
> venues. The claim is plainly both bunk & irrelevant to the human
> situation, as we've discussed before:
>
>
http://groups.google.com/groups?q=g:thl2169486412d&dq=&hl=en&lr=&safe=off&se
lm=69779556.0203241919.1a24ccb1%40posting.google.com
>
> ... and following discussion.
See in particular
http://groups.google.com/groups?dq=&hl=en&lr=&safe=off&selm=4ABn8.18030%24Dr
3.2460445%40news6-win.server.ntlworld.com&rnum=57
which Michael R never responded to.
Cheers,
Michael C Price
michaelprice
news:20020601191448...@mb-bd.aol.com...
> Michael Price:
> Chromium picolinate has reportedly extended a mammalian species
> maximum by 15% (see last ref)
> <snipped references>
>
> George Cherry:
> For whatever it's worth???
<snipped resistance-training and CrPic null study>
Compare with the 8 studies below. All are positive with the exception of
(2),
which confirms the lack of effectiveness of Cr Pic with restistance
training.
Search: "chromium picolinate" & "anderson"
1: Ravina A, Slezak L, Mirsky N, Bryden NA, Anderson RA. Related Articles
Reversal of corticosteroid-induced diabetes mellitus with supplemental
chromium.
Diabet Med. 1999 Feb;16(2):164-7.
PMID: 10229312 [PubMed - indexed for MEDLINE]
2: Campbell WW, Joseph LJ, Davey SL, Cyr-Campbell D, Anderson RA, Evans WJ.
Related Articles
Effects of resistance training and chromium picolinate on body composition
and skeletal muscle in older men.
J Appl Physiol. 1999 Jan;86(1):29-39.
PMID: 9887110 [PubMed - indexed for MEDLINE]
3: Anderson RA, Cheng N, Bryden NA, Polansky MM, Cheng N, Chi J, Feng J.
Related Articles
Elevated intakes of supplemental chromium improve glucose and insulin
variables in individuals with type 2 diabetes.
Diabetes. 1997 Nov;46(11):1786-91.
PMID: 9356027 [PubMed - indexed for MEDLINE]
4: Anderson RA. Related Articles
Nutritional factors influencing the glucose/insulin system: chromium.
J Am Coll Nutr. 1997 Oct;16(5):404-10. Review.
PMID: 9322187 [PubMed - indexed for MEDLINE]
5: Anderson RA, Bryden NA, Polansky MM. Related Articles
Lack of toxicity of chromium chloride and chromium picolinate in rats.
J Am Coll Nutr. 1997 Jun;16(3):273-9.
PMID: 9176835 [PubMed - indexed for MEDLINE]
6: Preuss HG, Grojec PL, Lieberman S, Anderson RA. Related Articles
Effects of different chromium compounds on blood pressure and lipid
peroxidation in spontaneously hypertensive rats.
Clin Nephrol. 1997 May;47(5):325-30.
PMID: 9181280 [PubMed - indexed for MEDLINE]
7: Lindemann MD, Wood CM, Harper AF, Kornegay ET, Anderson RA. Related
Articles
Dietary chromium picolinate additions improve gain:feed and carcass
characteristics in growing-finishing pigs and increase litter size in
reproducing sows.
J Anim Sci. 1995 Feb;73(2):457-65.
PMID: 7601779 [PubMed - indexed for MEDLINE]
8: Evock-Clover CM, Polansky MM, Anderson RA, Steele NC. Related Articles
Dietary chromium supplementation with or without somatotropin treatment
alters serum hormones and metabolites in growing pigs without affecting
growth performance.
J Nutr. 1993 Sep;123(9):1504-12.
PMID: 8360776 [PubMed - indexed for MEDLINE]
Cheers,
Michael C Price
Michael
"michaelprice" <michae...@ntlworld.com> wrote in message news:<TpfK8.3223$Ca.2...@newsfep1-win.server.ntli.net>...
I didn't respond because it didn't seem that most of the objections
raised were in fact cogent to the issues at hand -- & those that were,
were quite adequately addressed by Steve Harris. However:
Michael C Price wrote:
>
> "Michael" <mik...@lycos.com> wrote in message
> news:69779556.02032...@posting.google.com...
> >
> >> Effect of pantothenic acid on the longevity of mice by Richard B Pelton
> >> and Roger J Williams in Proc Soc Exp Biol & Med 99 632-633, 1958
> >> Result: 19.5% lifespan increase in a longlived mouse strain (C57).
> >>
> >> Favorable Effects of Pyridoxine HCl on the aging process by Lindseth K,
> >> Dictor M & Miquel J in AGE 5(4), 143, 1968
> >> Result: 11% total lifespan increase in a longlived strain (C57BL6J), even
> >> though only applied after 18 months (late middle age for mice).
> >>
> >> The Effect of Yeast Nucleic Acid on the Survival Time of 600-Day-Old
> >> Albino Mice by TS Gardner, Journal of Gerontology 3(?) (1946),
> >> pages 445-452
> >> Result: 16% lifespan increase
> >
> > The problem with these 3 experiments, in the present context, is that
> > none of them actually show any extension of normal lifespan. The
> > normal av'g lifespan of mice which are not genetic fuckups, & which
> > are properly cared for (not raised in intrinsically life-shortening
> > environments, as shown by shortened av'g LS for their strain), is in
> > the 31 month (942 day) ballpark.
>
> This assumes that the concept of a species LS has any relevance.
> It hasn't.
Since it's the subject under discussion, I find this statement
unproductive. You may not be interested in Islam, but it isn't useful
to introduce Islam in a discussion of religion as a factor in the
motivation for terrorism and then say that you think that religious
motivation for terrorism is irrelevant.
> The raising of the species maximum lifespan by the
> discovery (e.g. the "indy" gene) , or creation by selective breeding
> (ala Michael Rose), of a longer-lived strain within a species invalidates
> it as a meaningful yardstick.
I also find this statement unproductive. Obviously, intrinsic aging --
& hence max LS -- of a species is regulated precisely by its genetic
inheritance; hence, altering that inheritance will alter it. Genetic
changes are, of course, precisely how max LS comes to be determined (&
increased) in the course of speciation: random mutations interfacing
with selective pressures (rather than mutations &/or selective
pressures guided by human intelligence). If max LS were not
extendable, we'd be wasting our time altogether.
Again, analysis of human vs other primate genomes by Cutler and others
(informally, see Cutler RG, "The Molecular and Evolutionary Aspects of
Human Aging and Longevity," In _Anti-Aging Medicine_ (Larchmont, NY:
Mary Ann Liebert
Publishers, 1996) strongly suggests that the our species' max LS is
so much greater than other members of the relative to that of other
primates is similarly the result of the tweaking of a very small
number of largely regulatory genes. This doesn't change the fact that
chimps per se still have their old max LS.
& of course, we've long been able to extend max LS with CR -- which is
rather the point.
>
> > The "extended" av'g LS of Pelton & Williams' supplemented colony
> > was just 660 days, with no extension in their (also short) colony
> > "max LS."
>
> I question the veracity of your "max LS" figures. According to Walford
> (page 176, 120 yr diet) *NO* max LS figures were reported for the
> Pelton & Williams work.
I confess that I've overreached the data, here, and apologize. You're
correct that max LS data are not reported. But aside from the fact
that this, in itself, makes the paper irrelevant to the subject at
hand (ie provides, at most, no evidence on the subject), I think it
can reasonably (tho' not conclusively, & thus again apologies for
overstating the situation) be asserted that max LS cannot have been
extended, both because it is not credible that Williams would not have
reported such a result, & because when one extends max LS it's
difficult to get so drastically low a MEAN LS.
>
> > Similar considerations hold for the other experiments, above.
>
> I entertain similiar doubts for any unreferenced sources!
My sources are the ones that you cite. If you had looked up the papers
themselves, instead of relying on second-hand sources, you would know
this. I've presented the data previously to you.
>
> > Additionally, the Lindseth experiment reported lower BW in the B6
> > group: crypto-CR is likely at play in the paltry pseudo-extension
> > observed.
>
> Since the B6 was administered in drinking water this is not plausible.
Of course it is. It could make them nauseous, alter their satiety
sensors, alter their digestion (say, by damaging the nerves in teh GI
system leading to poor peristalsis), etc etc. Alternately, perhaps it
increased their activity level, which would both the low BW & the
increase in mean -- but not max -- LS. In any case: as max LS was not
extended, it's not a counterexample.
>
> BTW I don't call 11% LE when treatment begins in late middle
> age "paltry", but that's just a matter of "taste", I guess. :-)
Relative to the intervention under discussion (CR), & relative to the
NORMAL LS of well-cared-for rodents (& thus the prospects for a
normal, healthy human taking advantage of it as an intervention), it's
quite irrelevant.
>
> >> Composition and Biological Activity of Chromium-Pyridine Carboxylate
> >> Complexes by GW Evans and DJ Pouchnik, Journal of Inorganic
> >> Biochemistry 49, pg 177-187 (1993). This describes the action of
> >> dietary chromium picolinate on inhibiting glycation in rodents as they
> >> aged. Early indications of the
> >> lifespan increase (from the above experiment) were reported at the 22nd
> >> American Aging Association conference (Oct 1992), after the paper was
> >> submitted (March 1992) for publication, with further details in Chromium
> >> Picolinate by GW Evans ISBN 0895299119
> >
> > Alas, (a) the results were never properly published; (b) the
> > supplemented group's low bodyweights suggests that it was crypto-CR,
> > not Cr, doing the trick, and (c) Steve himself found no such effect:
>
> Steve's "controls" - for which criticism (a) applies!! - were on 10%
> restriction. Tragic since CR improves glucose tolerance.
Steve suggests that this level of CR does not affect glucose tolerance
in mice; if so, the objection fails, & Cr Pic looks even sillier as an
intervention as it can't even help out the LS of rodents w/ "normal"
age-associated loss of glucose tolerance.
If not, then it still isn't tragic, but an important methodological
necessity to interpret any increase in LS. If the controls will
otherwise become overweight & glucose intolerant, & the intervention
can improve the survival of the actives relative to the controls by
simply avoiding the obesity in the control group, false positives like
the others you cite are created (until one compares the group to a
healthy, normal cohort). I'm not interested in curing diabetes: I'm
interested in slowing down aging in healthy folks like me. If you're
diabetic, 1000 mcg Cr Pic/day is (on the balance of evidence) useful;
if you're not, it's a waste of money & a potentially toxic risk. It's
clearly not, on present evidence, an anti-aging intervention.
>
> For (b) see B6 comments for my scepticism of crypto-CR
Doesn't work as an argument for B6, as seen above; & the Cr Pic was in
food.
>
> > Anderson et al also would appear to have demonstrated that CrPic
> > doesn't extend LS (tho' I agree this is argumentum ab silentio):
>
> Max age of rats = 24 weeks explains lack of LE or any detectable
> effect!!!
Not at all. Gompertzian decline begins in rodents shortly after
weaning. If you're retarding aging, you should see it right away,
unless (again) you're mistreating your animals.
>
> The remaining CrPic counter-studies cited were not about LS.
... & hence aren't evidence on the subject at hand.
-Michael
michaelprice
>>>> Pelton and Roger J Williams in Proc Soc Exp Biol & Med 99
>>>> 632-633, 1958
>>>> Result: 19.5% lifespan increase in a longlived mouse strain (C57).
>>>>
>>>> Favorable Effects of Pyridoxine HCl on the aging process by
>>>> Lindseth K, Dictor M & Miquel J in AGE 5(4), 143, 1968
>>>> Result: 11% total lifespan increase in a longlived strain (C57BL6J),
>>>> even though only applied after 18 months (late middle age for
>>>> mice).
>>>>
>>>> The Effect of Yeast Nucleic Acid on the Survival Time of 600-Day-Old
>>>> Albino Mice by TS Gardner, Journal of Gerontology 3(?) (1946),
>>>> pages 445-452
>>>> Result: 16% lifespan increase
>>>
>>> The problem with these 3 experiments, in the present context, is that
>>> none of them actually show any extension of normal lifespan. The
>>> normal av'g lifespan of mice which are not genetic fuckups, & which
>>> are properly cared for (not raised in intrinsically life-shortening
>>> environments, as shown by shortened av'g LS for their strain), is in
>>> the 31 month (942 day) ballpark.
>>
>> This assumes that the concept of a species LS has any relevance.
>> It hasn't.
>
> Since it's the subject under discussion, I find this statement
> unproductive.
Saying (and then showing why) something is irrelevant is not
unproductive. I am explaining why I do not regard max species LS
as a gerontological "gold standard", by which you reject everything
except CR. Surely that is relevant?
Species LS is only relevant if aging is a constant across the species.
I see no reason for assuming this. Different strains have different
max LS. Just as each species, order, genus, family etc will have its
own max LS. Why not assume "intrinsic aging" is a constant across,
say, the genus?
> > The raising of the species maximum lifespan by the
> > discovery (e.g. the "indy" gene) , or creation by selective breeding
> > (ala Michael Rose), of a longer-lived strain within a species
> > invalidates it as a meaningful yardstick.
>
> I also find this statement unproductive. Obviously, intrinsic aging --
> & hence max LS -- of a species
Again you make the assumption that "intrinsic aging" is a constant
across the species. I consider it more likely that it varies from
individual to individual.
> is regulated precisely by its genetic
> inheritance; hence, altering that inheritance will alter it.
Same is true for each strain, genus, family, order, phylum, kingdom as
well as for each species. Should we regard their max LS as relevant?
Of course not.
[...]
> & of course, we've long been able to extend max LS with CR -- which is
> rather the point.
CR also raises avg LS.
>>> The "extended" av'g LS of Pelton & Williams' supplemented colony
>>> was just 660 days, with no extension in their (also short) colony
>>> "max LS."
>>
>> I question the veracity of your "max LS" figures. According to Walford
>> (page 176, 120 yr diet) *NO* max LS figures were reported for the
>> Pelton & Williams work.
>
> I confess that I've overreached the data, here, and apologize. You're
> correct that max LS data are not reported. But aside from the fact
> that this, in itself, makes the paper irrelevant to the subject at
> hand
If max species LS is the only standard to judge by, but that is
what I'm questioning.
> (ie provides, at most, no evidence on the subject), I think it
> can reasonably (tho' not conclusively, & thus again apologies for
> overstating the situation) be asserted that max LS cannot have been
> extended, both because it is not credible that Williams would not have
> reported such a result,
This was before Walford highlighted (erronously IMO) species max LS,
so it not such a surprise if max LSs were not reported back then.
> & because when one extends max LS it's difficult to get so drastically
> low a MEAN LS.
A small max LS could be accompanied by a small avg LS increase.
>>> Similar considerations hold for the other experiments, above.
>>
>> I entertain similar doubts for any unreferenced sources!
>
> My sources are the ones that you cite. If you had looked up the papers
> themselves, instead of relying on second-hand sources, you would know
> this. I've presented the data previously to you.
I don't know which sources you mean. I have all the Gardner and Evans
work (with one exception) to hand. You were the one inaccurately
reporting the Pelton & Williams work, not me. I have not been able to
get hold of the Lindseth et al original B6 papers, it's true, but its not
through lack of trying.
>>> Additionally, the Lindseth experiment reported lower BW in the B6
>>> group: crypto-CR is likely at play in the paltry pseudo-extension
>>> observed.
>>
>> Since the B6 was administered in drinking water this is not plausible.
>
> Of course it is. It could make them nauseous, alter their satiety
> sensors, alter their digestion (say, by damaging the nerves in teh GI
> system leading to poor peristalsis), etc etc.
If they were that sick I'd expect reduced LS, not increased LS.
Anyway, I didn't say impossible, just implausible considering the
dosage. You can consider that "crypto-CR is likely", whilst I shall
consider that it is unlikely. Neither of us knows for sure.
Another point. I'm taking a comparable dose of B6 daily. I don't
feel ill or nauseous - but if it induces crypto-CR in me I'd be delighted!!
> Alternately, perhaps it increased their activity level,
Not quite so unlikely, I suppose.
> which would both the low BW & the increase in mean -- but not max --
> LS. In any case: as max LS was not extended, it's not a counterexample.
Just let me clarify that, since, unfortunately, I have not been able to get
the Lindseth paper (yet). Which max LS was not extended? Cohort,
strain or species? Or is this just another of your assumptions, such as
you made above about the Pelton and Williams non-reporting of max
LS implying non-existence of max LS increase?
> > BTW I don't call 11% LE when treatment begins in late middle
> > age "paltry", but that's just a matter of "taste", I guess. :-)
>
> Relative to the intervention under discussion (CR), & relative to the
> NORMAL LS of well-cared-for rodents (& thus the prospects for a
> normal, healthy human taking advantage of it as an intervention), it's
> quite irrelevant.
11% in late middle age could easily translate into, say, 20% for more
youthful intervention. That, coupled with B5 & RNA (I shan't mention
CrPic yet), starts to look an impressive 40-ish years for a human -
certainly not "irrelevant".
>>>> Composition and Biological Activity of Chromium-Pyridine
>>>> Carboxylate Complexes by GW Evans and DJ Pouchnik, Journal
>>>> of Inorganic Biochemistry 49, pg 177-187 (1993). This describes
>>>> the action of dietary chromium picolinate on inhibiting glycation in
>>>> rodents as they aged. Early indications of the lifespan increase
>>>> (from the above experiment) were reported at the 22nd
>>>> American Aging Association conference (Oct 1992), after the paper
>>>> was submitted (March 1992) for publication, with further details in
>>>> Chromium Picolinate by GW Evans ISBN 0895299119
>>>
>>> Alas, (a) the results were never properly published; (b) the
>>> supplemented group's low bodyweights suggests that it was crypto-CR,
>>> not Cr, doing the trick, and (c) Steve himself found no such effect:
>>
>> Steve's "controls" - for which criticism (a) applies!! - were on 10%
>> restriction. Tragic since CR improves glucose tolerance.
>
> Steve suggests that this level of CR does not affect glucose tolerance
> in mice; if so, the objection fails, & Cr Pic looks even sillier as an
> intervention as it can't even help out the LS of rodents w/ "normal"
> age-associated loss of glucose tolerance.
My response to Steve's points can be found on the original thread.
Just tackling Michael's comments:
> If not, then it still isn't tragic, but an important methodological
> necessity to interpret any increase in LS. If the controls will
> otherwise become overweight & glucose intolerant,
as humans do. Look around!
> & the intervention
> can improve the survival of the actives relative to the controls by
> simply avoiding the obesity in the control group, false positives like
> the others you cite are created (until one compares the group to a
> healthy, normal cohort). I'm not interested in curing diabetes:
I am, since I believe that a typical human becomes pre-diabetic
as they age, with decreasing glucose tolerance response curves.
> I'm interested in slowing down aging in healthy folks like me.
Will your glucose tolerance curves at 60 be the same as at 20,
healthy or not?
You might not believe the LS results with CrPic since it has not
properly been reported, but its effectiveness in reducing glycation
was reported in the peer-reviewed literature.
Glycation is almost certainly one of the sources of aging, hence
CrPic, plausibly, should slow down aging.
> If you're diabetic, 1000 mcg Cr Pic/day is (on the balance of
> evidence) useful; if you're not, it's a waste of money & a potentially
> toxic risk. It's clearly not, on present evidence, an anti-aging
intervention.
No, it is just not clearly an anti-aging intervention. We can't be sure.
Again, you overstate your case.
> > For (b) see B6 comments for my scepticism of crypto-CR
>
> Doesn't work as an argument for B6, as seen above; & the Cr Pic
> was in food.
What I meant was that since you had previously shown an inordinate
fondness for labelling any LS increase as crypto-CR --- an intrinsically
unfalsifiable position at present --- I was entitled to be sceptical of this
blanket crypto-CR designation applied yet again. And again I'd be
delighted if CrPic was a crypto-CR LEer.
>>> Anderson et al also would appear to have demonstrated
>>> that CrPic doesn't extend LS (tho' I agree this is argumentum ab
>>> silentio):
>>
>> Max age of rats = 24 weeks explains lack of LE or any detectable
>> effect!!!
>
> Not at all. Gompertzian decline begins in rodents shortly after
> weaning. If you're retarding aging, you should see it right away,
> unless (again) you're mistreating your animals.
I'm still amazed that you can cite that experiment as a null LS test
for chromium picolinate. It would take a very large sample to
produce a significant effect. I wouldn't be surprised if no rats
(including controls) died before being sacrificed at 24 weeks.
Cheers,
Michael C Price
Tom Matthews
[big snip]
> I'm not interested in curing diabetes: I'm
> interested in slowing down aging in healthy folks like me. If you're
> diabetic, 1000 mcg Cr Pic/day is (on the balance of evidence) useful;
> if you're not, it's a waste of money & a potentially toxic risk.
While this is likely true for those below 40-50, for older humans who all tend
to become insulin resistant with age, I think that, at the least, a few hundred
mg of Cr daily (not necessarily all Pic) may be a useful prophylactic. My own
current dosage is 300 mg Cr Pic plus 300 mg Cr polynicotinate which, on the
evidence, I think is both beneficial and safe for someone my age.
> It's clearly not, on present evidence, an anti-aging intervention.
As I have stated before (many times) all your statements about what is, or is
not "antiaging" are based on the narrow technical definition of "aging" used
within the science of gerontology, *not* the vernacular definition of "aging"
which has been in our natural language far longer and which most people use.
Thus, many of the arguments, even on this group are more of a semantic nature
rather than a scientific dispute.
From the point of view of the standard vernacular definition an intervention is
"antiaging" if it changes the signs and symptoms characteristic of aged decline
back to younger levels. This generally means that it also increases the health
and well being, and/or extends the life of an elderly individual.
However, extending life span without any change in the signs and symptoms of
aging (ie increased quality of life), would not likely be thought to be
antiaging under this vernacular definition. To a certain extent that is what is
currently being done with geriatric care - it is extending lifespan by a few
months or years, but without any major change to the parameters of aged decline.
I don't think that anyone would call this antiaging.
EXTREME EXAMPLE: If the medical establishment had gone all out to hover over
Jeanne Calment and keep her alive longer, even though this would have increased
the species maximum lifespan for humans, would it really have been "antiaging"
by *any* reasonable definition!
michaelprice
with Michael (Rae?).
I am not against using extension of the species maximum LS as an indicator
of slowing the aging process, but I do object to taking the absence of any
such transgression as "proof" that some treatment or supplement is not
effective.
Clearly any treatment, such as CR or (reportedly) chromium picolinate, which
busts the species maximum LS (on any strain) is having a beneficial effect
on the aging process. However a treatment that fails to break the species
maximum LS may fail because the strain used may be aging more rapidly than
some naturally longer-lived strains, or simply because the sample size was
not large enough. Of course it could also be an ineffective treatment.
In other words, max species LS is a good positive test, but a bad negative
test.
Cheers,
Michael C Price
"michaelprice" <michae...@ntlworld.com> wrote in message
news:O7zK8.5128$nQ6.2...@newsfep1-win.server.ntli.net...
michaelprice
> out to hover over Jeanne Calment and keep her alive longer, even
> though this would have increased the species maximum lifespan for humans,
> would it really have been "antiaging" by *any* reasonable definition!
That depends how they might have done it. With organ transplants,
then no, it would have not been antiaging. But if by metabolic intervention
(B-vits, ALT711, selenium, chromium etc etc ), then it might be classified
antiaging.
Cheers,
Michael C Price
Tom Matthews
I agree, Michael, but by using the term "establishment" I
automatically precluded the use of supplements or other unconventional
and non-mainstream approaches.
michaelprice
news:3D06E764...@morelife.org...
> michaelprice wrote:
>
> >>EXTREME EXAMPLE: If the medical establishment had gone all
> >>out to hover over Jeanne Calment and keep her alive longer, even
> >>though this would have increased the species maximum lifespan for
humans,
> >>would it really have been "antiaging" by *any* reasonable definition!
> >>
> >
> > That depends how they might have done it. With organ transplants,
> > then no, it would have not been antiaging. But if by metabolic
intervention
> > (B-vits, ALT711, selenium, chromium etc etc ), then it might be
classified
> > antiaging.
>
> I agree, Michael, but by using the term "establishment" I
> automatically precluded the use of supplements or other unconventional
> and non-mainstream approaches.
Hah! Good point :-)
Cheers,
Michael C Price