CR Research Update
Ian Goddard
Caloric restriction in primates.
Lane MA, Black A, Handy A, Tilmont EM, Ingram DK, Roth GS.
Laboratory of Neurosciences, Gerontology Research Center, National
Institute on Aging, National Institutes of Health, Baltimore, Maryland
21224, USA. ML...@vms.grc.nia.nih.gov
Caloric restriction (CR) remains the only nongenetic intervention
that reproducibly extends mean and maximal life span in short-lived
mammalian species. This nutritional intervention also delays the
onset, or slows the progression, of many age-related disease
processes. The diverse effects of CR have been demonstrated many
hundreds of times in laboratory rodents and other short-lived species,
such as rotifers, water fleas, fish, spiders, and hamsters. Until
recently, the effects of CR in longer-lived species, more closely
related to humans, remained unknown. Long-term studies of aging in
nonhuman primates undergoing CR have been underway at the National
Institute on Aging (NIA) and the University of Wisconsin-Madison (UW)
for over a decade. A number of reports from the NIA and UW colonies
have shown that monkeys on CR exhibit nearly identical physiological
responses as reported in laboratory rodents. Studies of various
markers related to age-related diseases suggest that CR will prevent
or delay the onset of cardiovascular disease, diabetes, and perhaps
cancer, and preliminary data indicate that mortality due to these and
other age-associated diseases may also be reduced in monkeys on CR,
compared to controls. Conclusive evidence showing that CR extends life
span in primates is not presently available; however, the emerging
data from the ongoing primate studies strengthens the possibility that
the diverse beneficial effects of CR on aging in rodents will also
apply to nonhuman primates and perhaps ultimately to humans.
******************************************************************
Chem Senses 2002 Mar;27(3):299-306
DNA microarray analysis of the aging brain.
Prolla TA.
Departments of Genetics and Medical Genetics, University of
Wisconsin, 445 Henry Mall, Madison, WI 53706, USA.
To examine molecular events associated with brain aging and its
retardation by caloric restriction (CR), we have employed high-density
oligonucleotide arrays providing data on 6347 genes to define
transcriptional patterns in two brain regions (cerebellum and
neocortex). Male C57BL/6 mice were either fed normally or subjected
to CR. To investigate aging, 5 month (young adult) and 30 month-old
normally fed mice were compared. To study CR, 30 month-old control
and CR mice were compared. In both brain regions, aging resulted in
a gene expression profile suggestive of a marked inflammatory
response, oxidative stress and reduced neuronal plasticity and
neurotrophic support. In the brain, CR selectively attenuated the
age-associated induction of genes encoding inflammatory and stress
responses. In addition to providing an improved understanding of the
aging process, the use of DNA microarrays generates panels of hundreds
of transcriptional biomarkers of molecular aging, providing a new tool
to measure biological age on a tissue-specific basis. These studies
suggest that genomic approaches may be useful in understanding the
molecular basis of the aging process in experimental animals.
******************************************************************
Circulation 2002 Feb 5;105(5):564-9
Weight loss reduces C-reactive protein levels in obese postmenopausal
women.
Tchernof A, Nolan A, Sites CK, Ades PA, Poehlman ET.
Department of Medicine, College of Medicine, University of Vermont,
Burlington.
BACKGROUND: C-reactive protein (CRP) has been proposed as an
independent risk factor for cardiovascular disease and has been
positively associated with body weight and body fatness. We examined
the hypothesis that weight loss would reduce plasma CRP levels in
obese postmenopausal women. METHODS AND RESULTS: In a sample of 61
obese (body mass index, 35.6 +/- 5.0 kg/m(2)), postmenopausal women
(age, 56.4 +/- 5.2 years), we found that plasma CRP levels were
positively associated with dual x-ray absorptiometry-measured total
body fatness (r=0.36, P<0.005) and CT-measured intra-abdominal body
fat area (r=0.30, P<0.02). Significant correlations were also found
between plasma CRP and triglyceride levels (r=0.33, P<0.009) and
glucose disposal measured by the hyperinsulinemic-euglycemic clamp
technique (r=-0.29, P<0.03). Twenty-five of the 61 women tested at
baseline completed a weight loss protocol. The average weight loss was
14.5 +/- 6.2 kg (-15.6%, P<0.0001), with losses of 10.4 +/- 5.4 kg fat
mass (-25.0%, P<0.0001) and 2.8 +/- 1.4 kg fat-free mass (-6.0%,
P<0.0001). Visceral and subcutaneous fat areas were reduced by -36.4%
and -23.7%, respectively (P<0.0001). Plasma CRP levels were
significantly reduced by weight loss: average -32.3%, from 3.06
(+0.69, -1.29) to 1.63 (+0.70, -0.75) microgram/mL (P<0.0001, medians
and interquartile differences). Changes in body weight and in total
body fat mass were both positively associated with plasma CRP level
reductions. CONCLUSIONS: Adiposity was a significant predictor of
plasma CRP in postmenopausal women on a cross-sectional basis.
Moreover, caloric restriction-induced weight loss decreased plasma CRP
levels. Weight loss may represent an important intervention to reduce
CRP levels, which may mediate part of its cardioprotective effects in
obese postmenopausal women.
******************************************************************
Exp Gerontol 2002 May;37(5):639-45
Oxidative phosphorylation enzyme complexes in caloric restriction.
Olgun A, Akman S, Serdar MA, Kutluay T.
Department of Biochemistry and Clinical Biochemistry, Gulhane School
of Medicine, Etlik-06018, Ankara, Turkey
Free radicals, generated especially by electron leakage from
mitochondrial electron transport chain (ETC), are accepted as one of
the possible causes of aging. Long-term caloric restriction (CR) is
known to increase the species specific average and maximum life spans.
Thus it provides a means for investigating mechanisms of aging. There
is evidence suggesting a decrease in the free radical production with
CR. In this study, Blue-Native PAGE (BN-PAGE) technique was used to
investigate the effect of CR on the oxidative phosphorylation enzyme
complexes. Of the total 30 female Swiss Albino balb/c mice, 15 were
used as control and the other 15 as CR group. Alternate day feeding
regimen was used in the CR group for 66 weeks beginning at the end of
3rd month. In the control group, 5 (33.3%) mice died, 3 (20%) of them
of breast cancer, 2 (13.3%) of unknown causes and no death cases were
observed in the CR group during the study. BN-PAGE was performed on
the extracts from brain mitochondrial fractions. Complexes II and V
were excluded from the study due to some analytical limitations. No
difference was found in the levels of complexes I and III between the
groups. In the CR group, complex IV level was found increased and the
ratio of complex III-IV decreased compared with the control group.
Since there is a slight increase (108%) in the level of complex IV in
the CR group, our results could suggest possible partial compensation
of electron leakage in the upstream complexes in ETC, and the decrease
of free radical production with CR.
******************************************************************
What's with this next study? ...
******************************************************************
Brain Res 2002 Mar 22;931(1):32-40
Caloric restricted male rats demonstrate fewer synapses in layer
2 of sensorimotor cortex.
Shi L, Poe BH, Constance Linville M, Sonntag WE, Brunso-Bechtold JK.
Department of Neurobiology and Anatomy, Medical Center Boulevard, Wake
Forest University School of Medicine, 27157-1010, Winston-Salem, NC,
USA
Previous studies have demonstrated an age-related decline in the
density of presumptive inhibitory synapses in layer 2 of rat
sensorimotor cortex [J. Comp. Neurol. 439(1) (2001) 65]. Caloric
restriction has been shown to ameliorate age-related deterioration in
a variety of systems and to extend life span. The present study tested
the hypothesis that caloric restriction would prevent the previously
reported age-related synaptic decline. Accordingly, synaptic density
in layer 2 of sensorimotor cortex was compared between 29-month-old
male rats fed ad libitum and 29-month-old male rats that were caloric
restricted (60% of ad libitum calories) from 4 months of age. In
serial electron micrographs, the physical disector was used to
determine the numerical density of presumptive excitatory and
inhibitory synapses (those containing round or nonround vesicles,
respectively) as well as that of neurons. Not only was the previously
reported age-related decline in numerical density of presumptive
inhibitory synapses not ameliorated by caloric restriction, the
numerical density was significantly lower in caloric restricted than
in ad libitum fed rats for total as well as for presumptive excitatory
and inhibitory synapses. Analysis further revealed no difference in
the numerical density of neurons in this region. Relating synapse
density to neuron density as the ratio of synapses to neuron also
demonstrated significantly fewer synapses per neuron in caloric
restricted than in ad libitum fed old rats. Finally, synapse length
was significantly less in caloric restricted rats. These results
suggest that not only does caloric restriction fail to prevent the
age-related decline in presumptive inhibitory synapses, it results in
fewer presumptive excitatory synapses as well.
******************************************************************
Ann N Y Acad Sci 2001 Apr;928:305-15
Caloric restriction in primates and relevance to humans.
Roth GS, Ingram DK, Lane MA.
Laboratory of Neurosciences, Gerontology Research Center, National
Institute on Aging, National Institutes of Health, Baltimore,
Maryland 21224, USA. ge...@vax.grc.nia.nih.gov
Dietary caloric restriction (CR) is the only intervention conclusively
and reproducibly shown to slow aging and maintain health and vitality
in mammals. Although this paradigm has been known for over 60 years,
its precise biological mechanisms and applicability to humans remain
unknown. We began addressing the latter question in 1987 with the
first controlled study of CR in primates (rhesus and squirrel monkeys,
which are evolutionarily much closer to humans than the rodents most
frequently employed in CR studies). To date, our results strongly
suggest that the same beneficial "antiaging" and/or "antidisease"
effects observed in CR rodents also occur in primates. These include
lower plasma insulin levels and greater sensitivity; lower body
temperatures; reduced cholesterol, triglycerides, blood pressure, and
arterial stiffness; elevated HDL; and slower age-related decline in
circulating levels of DHEAS. Collectively, these biomarkers suggest
that CR primates will be less likely to incur diabetes, cardiovascular
problems, and other age-related diseases and may in fact be aging more
slowly than fully fed counterparts. Despite these very encouraging
results, it is unlikely that most humans would be willing to maintain
a 30% reduced diet for the bulk of their adult life span, even if it
meant more healthy years. For this reason, we have begun to explore CR
mimetics, agents that might elicit the same beneficial effects as CR,
without the necessity of dieting. Our initial studies have focused on
2-deoxyglucose (2DG), a sugar analogue with a limited metabolism that
actually reduces glucose/energy flux without decreasing food intake in
rats. In a six-month pilot study, 2DG lowered plasma insulin and body
temperature in a manner analagous to that of CR. Thus, metabolic
effects that mediate the CR mechanism can be attained
pharmacologically. Doses were titrated to eliminate toxicity; a
long-term longevity study is now under way. In addition, data from
other laboratories suggest that at least some of the same
physiological/metabolic end points that are associated with the
beneficial effects of underfeeding may be obtained from other
potential CR mimetic agents, some naturally occurring in food
products. Much work remains to be done, but taken together, our
successful results with CR in primates and 2DG administration to rats
suggest that it may indeed be possible to obtain the health- and
longevity-promoting effects of the former intervention without
actually decreasing food intake.
******************************************************************
Ann N Y Acad Sci 2001 Apr;928:316-26
Aging and caloric restriction in nonhuman primates: behavioral
and in vivo brain imaging studies.
Ingram DK, Chefer S, Matochik J, Moscrip TD, Weed J, Roth GS,
London ED, Lane MA.
Laboratory of Neurosciences, Gerontology Research Center, National
Institute on Aging, National Institutes of Health, Baltimore,
Maryland 21224, USA. do...@vax.grc.nia.nih.gov
In a long-term longitudinal study of aging in rhesus monkeys, a
primary objective has been to determine the effects of aging and
caloric restriction (CR) on behavioral and neural parameters. Through
the use of automated devices, locomotor activity can be monitored in
the home cages of the monkeys. Studies completed thus far indicate a
clear age-related decline in activity consistent with such
observations in many other species, including humans. However, no
consistent effects of CR on activity have been observed. Selected
groups of monkeys have also been involved in brain imaging studies,
using magnetic resonance imaging (MRI) and positron emission
tomography (PET). MRI studies completed thus far reveal a clear
age-related decline in the volumes of the basal ganglia, the putamen,
and the caudate nucleus, with no change in total brain volume. PET
analysis has revealed an age-related decline in the binding potential
of dopamine D2 receptors in the same brain regions. These results are
consistent with findings in humans. Although additional longitudinal
analysis is needed to confirm the present results, it would appear
that locomotor activity, volume of the basal ganglia, as well as
dopamine D2 receptor binding potential provide reliable, noninvasive
biomarkers of aging in rhesus monkeys.
******************************************************************
"To lengthen thy life, lessen thy meals." Ben Franklin
http://www.ultraHIQ.net/Ubiquity/Winter02/CR.html
Ian Goddard
Notice that in the following anomalous study (anomalous because
it is a rare case of finding a negative result for CR) the rats
were introduced to CR during an adolescent age range (4 months)
and two features necessary for later-onset CR to yield positive
results are not mentioned as having occurred, (1) CR must be
introduced gradually, and (2) a CR diet must be nutrient
enriched. Assuming both factors were neglected in the study as
citing them is in the abstract, what we would be looking at is
sudden starvation imposed upon adolescent brains, which should
result in negative outcomes. I sent an inquiry to Dr Lei Shi.
michaelprice
news:3ca65e2e....@news.erols.com...
> Ann N Y Acad Sci 2001 Apr;928:287-95
>
> Caloric restriction in primates.
>
> Lane MA, Black A, Handy A, Tilmont EM, Ingram DK, Roth GS.
>
> Laboratory of Neurosciences, Gerontology Research Center, National
> Institute on Aging, National Institutes of Health, Baltimore, Maryland
> 21224, USA. ML...@vms.grc.nia.nih.gov
>
> Caloric restriction (CR) remains the only nongenetic intervention
> that reproducibly extends mean and maximal life span in short-lived
> mammalian species.
Not so. Wrong on both counts. Nucleic acid enriched diets have
reproducibly extended mean and maximum lifespan in mice.
First done by Robertson, repeated by Gardner. Basic difference
was Gardner started on adult mice and lowered the dosage.
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.
Influence of Nucleic Acids of Various Origin upon the Growth and Longevity
of the white mouse by TB Robertson in the Australian J of Experimental
Biology and Medical Science, 5 pg 46-67, 1928
Cheers,
Michael C Price
Ian Goddard
IAN: That's interesting Mike. However, there's a couple
shortfalls in the case you've presented. First, simply
quoting two study titles has not established that either
study found an intervention-induced extension of maximum
lifespan. Indeed, neither title even indicates what the
results were. Secondly, if we assume that both studies
did find an extension of maximum lifespan, notice that
the abstract I posted that you quoted part of also said:
"The diverse effects of CR have been demonstrated many
hundreds of times." Reproducibility is only vaguely
suggested by one single instance of replication.
While it may be that you've found something that was
wrongfully passed over by science, if nucleic-acid-
enriched diets are comparable to CR, one is left to
wonder how gerontologists managed to overlook this.
Do you have any more information on this intervention?
Thomas Carter
My guess is that there are some negative results on nucleoside
supplementation that are unpublished and others that are hard to find.
I can hardly belive these early, positive results were not followed up
on. This is what I have on the subject.
Supplements claimed to; boost immunity, increase energy, neutralize
toxins, repair cell damage and improve skin elasticity as well as
improve memory in the elderly and more rapid healing.
The four nucleosides are Adenine, Guanine, Thymine, and Cytosine. The
four basic nucleosides are combined with a sugar (ribose or
deoxyribose) and become nucleotides. They then go to DNA, RNA, or the
mitochondria to be used in energy transfer. They breakdown to uric
acid, a powerful antioxidant.
Faster healing and immunity boost were apparently demonstrated in two
small but good studies. Transplant patients were fed a nucleotide free
diet and their immune system was depressed.
High levels cause more Uric acid which could cause gout.
See LEF mag August '97 page 5
And this abstract
Toxicology 1975;3(3):341-7 Long-term feeding study on disodium
5-ribonucleotide in dogs. Worden AN, Rivett KF, Edwards DB, Street AE,
Newman AJ. Groups of 4 male and 4 female Beagle dogs were fed for 2
years on diets containing 0 (control), 0.1, 1.0 and 2.0%,
respectively, of disodium 5'-ribonucleotide (a 50 : 50 mixture of
disodium 5'-inosinate and disodium 5'-guanylate). The mean daily
intakes of the 3 test groups ranged during the experiment from
0.04-0.03, 0.48-0.26 and 0.93-0.51 g/kg, respectively. No effects
attributable to treatment were found in mortality, food consumption,
water consumption, bodyweight gain, ophthalmoscopy, clinical signs,
haematology, serum chemistry (other than allantoin levels), organ
weights, macroscopic pathology or histology, Small differences were
observed between mean values in treatment and control dogs for serum
allantoin but there was no indication of any persistent significant
difference throughout the 2-year study. In a 6-week preliminary test,
dietary levels of up to 10% disodium 5'-ribonucleotide were without
detectable adverse effect upon beagle dogs of either sex. PMID:
1124541
Thomas
michaelprice
>> Not so. Wrong on both counts. Nucleic acid enriched diets
>> have reproducibly extended mean and maximum lifespan in
>> mice. First done by Robertson, repeated by Gardner. Basic
>> difference was Gardner started on adult mice and lowered
>> the dosage.
>>
>> 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.
>>
>> Influence of Nucleic Acids of Various Origin upon the Growth
>> and Longevity of the white mouse by TB Robertson in the
>> Australian J of Experimental Biology and Medical Science, 5
>> pg 46-67, 1928
>>
>>
>>Cheers,
>>Michael C Price
>
>
> IAN: That's interesting Mike. However, there's a couple
> shortfalls in the case you've presented. First, simply
> quoting two study titles has not established that either
> study found an intervention-induced extension of
> maximum lifespan.
I'm not impressed by maximum lifespan, but for those
that are, Robertson did get an approx 5-10% extension
in cohort maximum lifespan.
My doubts as to the validity of maximal measures
are because the raising of the species maximum lifespan by
discovery of a longer-lived strain within the species
(e.g. the "indy" gene), or creation by selective breeding (ala
Michael Rose), invalidates the species maximum as a
meaningful yardstick. Also the control and cohort maximum
lifespan are both subject to too much random scatter or
uncertainty - by definition since only one animal defines the
maximum in a relatively small group - and hence invalidates
them both as meaningful measures.
> Indeed, neither title even indicates what the
> results were.
16% rise in mean lifespan for mice fed 25mg/d
if yeast extract nucleic acid. Gardner reproduced same
with more enriched basal diet and smaller dose (2.5mg/d).
Human equivalent dose = 250mg/d
> Secondly, if we assume that both studies
> did find an extension of maximum lifespan, notice that
> the abstract I posted that you quoted part of also said:
> "The diverse effects of CR have been demonstrated many
> hundreds of times." Reproducibility is only vaguely
> suggested by one single instance of replication.
I'm not knocking CR's reproducibility, although I did find
the synapse reduction effect mildly worrying. If I was on
CR I would have found that alarming! (Or stultifying...)
> While it may be that you've found something that was
> wrongfully passed over by science, if nucleic-acid-
> enriched diets are comparable to CR, one is left to
> wonder how gerontologists managed to overlook this.
Because it doesn't fit into the free-radical paradigm that
held/holds sway in gerontology. Also unpatentable so no
commercial funding for research.
Also it wasn't overlooked by Dr Benjamin S Frank who wrote
a couple of books on the subject, but his stuff seemed to
go out of fashion after he died young, apparently of diabetic
complications.
See
Nucleic Acid Therapy in Aging and Degenerative Disease
&
Dr Franks No Aging Diet (with Philip Miele)
ISBN 0803753497
Cheers,
Michael C Price
Ian Goddard
It seems that the study (below) that found a reduced number of
synapses in layer 2 of sensorimotor cortex in 60% CR mice did
follow the proper protocol of gradual CR onset and a nutrient-
enriched diet. Looking for some explanation, 60% CR is a very
high rate. Most studies I've seen involve a lower rate. This
negative effect was also found in one brain region. Given the
clearly established overall benefits of CR to aging animal
brain, one must assume that despite this (assuming this effect
always exists), the overall benefits outweigh negative effects.
However, this has to raise questions regarding the neurological
problem that has manifested in one of the leading proponents of
CR, Dr Roy Walford. His problem makes it impossible for him to
maintain balance without support. He attributes it to exposure
to a gas in the Biosphere II experiment, but I think that's just
a hypothesis. Don't have time to explore this... does anyone know
what functions layer 2 of the sensorimotor cortex is involved in?
Here's the reply I got from the lead researcher in the study...
On Mon, 01 Apr 2002 09:24:03 -0500 lshi@w... (Lei Shi) writes:
> Hello, below are the answers to your questions:
>
> 1. how rapidly was the 60% caloric restriction introduced to the
> rats at 4 months age?
>
> A: Beginning at 4 months of age, and over a 3-week period, the
> intake of caloric restricted rats was reduced to 60% of the calories
> consumed by the ad libitum rats.
>
> 2. Were the CR rats given a nutrient enriched diet?
>
> A: The diet of caloric restricted rats was supplemented with
> vitamins and minerals to assure proper intake of essential nutrients.
>
> I hope that helps and detailed description of the CR regimen can be
> found in the paper, please don't hesitate to contact me if you have
> further questions.
>
> Lei Shi
michaelprice
of CR - the authors do not say they looked elsewhere and that
was the rest of the brain was okay, which surely they would
mentioned if it checked out fine.
The brain uses more energy than any other organ.
(2% of body weight, yet consumes 20% of the energy) So,
faced with the energy restriction imposed by CR, what does any
sensible body do? Throttle the brain back by lowering synaptic
density.
Walford's nascent ALS (?) sounds like a consequence rather
than a co-incidence.
BTW the authors noted a decrease in synapse *length* as well
as density. I don't know what they mean by synaptic length.
Area or volume would make more sense, wouldn't it?
Cheers,
Michael C Price
Ian Goddard
>I suspect that neurological impairment is a general consequence
>of CR - the authors do not say they looked elsewhere and that
>was the rest of the brain was okay, which surely they would
>mentioned if it checked out fine.
IAN: Well, you have to look at this one study in a context
that includes all CR/brain studies, wherein the overwhelming
picture essentially proves (through the sheer volume of
replication) that in general, CR extends the lifespan of
animal-brain functions. This is so true, CR is used as a tool
to study brain aging (not to study CR), since if you can alter
aging, as you can with CR, you can find out what it is and what
it does. In this case it seems we may be finding a problem area.
I have now found other studies that explored actual malnutrition
that suggests the sensorimotor cortex is highly susceptible to
pruning resulting from significant energy/protein reductions.
Another thought, in the hundreds of CR studies, surely it would
have been noted that the CR mice became deficient in some area
corresponding to sensorimotor cortex functions, like, perhaps
balance. In quick searchers, I could not find a link between
the sensorimotor cortex and balance, but just the name of
the region suggests a connection to balance, and thus
perhaps to the balance problem that Dr Walford has.
Ian Goddard
>> Indeed, neither title even indicates what the
>> results were.
>
>16% rise in mean lifespan for mice fed 25mg/d
>if yeast extract nucleic acid. Gardner reproduced same
>with more enriched basal diet and smaller dose (2.5mg/d).
>Human equivalent dose = 250mg/d
IAN: Surely there was some follow-up research. No?
>> While it may be that you've found something that was
>> wrongfully passed over by science, if nucleic-acid-
>> enriched diets are comparable to CR, one is left to
>> wonder how gerontologists managed to overlook this.
>
>Because it doesn't fit into the free-radical paradigm that
>held/holds sway in gerontology. Also unpatentable so no
>commercial funding for research.
IAN: But CR is also unpatentable and has not fit into
the free-radical paradigm (although one study I posted
indicated how it may), and those limitations obviously
did not stop CR from becoming one of the main tools in
gerontological research. Just the fact that x can slow
aging is sufficient to make it valuable in aging research.
Ian Goddard
> I have now found other studies that explored actual malnutrition
> that suggests the sensorimotor cortex is highly susceptible to
> pruning resulting from significant energy/protein reductions.
However, here's an abstract of a study I have in full
that reports: "Dietary restriction was found to retard
age-associated decline of sensorimotor coordination..."
As is the case with most research involving CR, notice
that the objective of this study was not to examine the
effects of CR. Instead, CR was being used as a tool to
study a hypothesis about the aging process, reflecting
the fact that the efficacy of CR as a means to retard
brain-aging processes is a generally accepted fact.
Arch Biochem Biophys 1996 Sep 1;333(1):189-97
Effect of age and caloric intake on protein oxidation in different
brain regions and on behavioral functions of the mouse.
Dubey A, Forster MJ, Lal H, Sohal RS.
Department of Biological Sciences, Southern Methodist University,
Dallas, Texas 75275, USA.
The objective of this study was to determine if oxidative
stress/damage is a possible causal factor in the senescence-related
loss of brain functions in the mouse. If such a relationship indeed
existed, it was expected that oxidative protein damage would increase
with age within regions of the brain associated with
senescence-related functional loss, and that calorie restriction, an
intervention which retards certain aspects of age-associated
functional loss, would reverse such increases. Dietary restriction was
found to retard age-associated decline of sensorimotor coordination
and improve performance of aged mice on an avoidance learning problem.
Protein carbonyl concentration, one measure of protein oxidation,
increased from 8 to 27 months of age in most regions of the mouse
brain, with the most notable increases occurring in the striatum and
hippocampus, regions of the brain strongly implicated in
age-associated functional loss. Age-associated loss of protein
sulfhydryls was more uniform across brain regions and did not involve
the hippocampus. Dietary restriction resulted in reversal of the
age-associated regional trends in carbonyl and sulfhydryl
concentration, with the largest changes occurring within the striatum.
Cross over studies in aged calorie restricted and ad libitum fed mice
indicated that lowering of carbonyl content by calorie restriction
could be induced or reversed within a time frame of 3 to 6 weeks.
These findings suggest that the beneficial effects of dietary
restriction upon brain function and life span may depend upon its
ability to acutely reduce steady-state levels of oxidative stress.
michaelprice
> On Mon, 1 Apr 2002, "michaelprice" <michae...@ntlworld.com> wrote:
>
>> I suspect that neurological impairment is a general
>> consequence of CR - the authors do not say they looked
>> elsewhere and that was the rest of the brain was okay,
>> out fine.
>
> IAN: Well, you have to look at this one study in a context
> that includes all CR/brain studies, wherein the overwhelming
> picture essentially proves (through the sheer volume of
> replication) that in general, CR extends the lifespan of
> animal-brain functions. This is so true, CR is used as a tool
> to study brain aging (not to study CR), since if you can alter
> aging, as you can with CR, you can find out what it is and what
> it does. In this case it seems we may be finding a problem area.
> I have now found other studies that explored actual malnutrition
> that suggests the sensorimotor cortex is highly susceptible to
> pruning resulting from significant energy/protein reductions.
What about the rest of the cortex? Please keep us informed.
Malnutrition studies on humans or other animals?
> Another thought, in the hundreds of CR studies, surely it would
> have been noted that the CR mice became deficient in some area
> corresponding to sensorimotor cortex functions, like, perhaps
> balance.
Here's an unpleasant thought. Animal studies will not show the
CR-induced neurological impairment because they have a
much lower brain-body ratio. Perhaps only humans are
susceptible to CR brain-rot.
> In quick searchers, I could not find a link between
> the sensorimotor cortex and balance, but just the name of
> the region suggests a connection to balance, and thus
> perhaps to the balance problem that Dr Walford has.
Cheers,
Michael C Price
Ian Goddard
>> ... In this case it seems we may be finding a problem area.
>> I have now found other studies that explored actual malnutrition
>> that suggests the sensorimotor cortex is highly susceptible to
>> pruning resulting from significant energy/protein reductions.
>
>
> However, here's an abstract of a study I have in full
> that reports: "Dietary restriction was found to retard
> age-associated decline of sensorimotor coordination..."
Here then is a study that has similar findings to that of
Dr Lei Shi's study. But notice, the dietary intervention
here is referred to as "malnutrition." If you follow the
link below to the NLM and click on "related studies,"
you'll find a number of similar findings, though all
seem to define the intervention as "malnutrition." In
light of the overwhelming body of positive findings for
CR, and the one exception quoted earlier in this thread,
I'm inclined to hypothesize that for some reason the mice
in Dr Shi's study were experiencing malnutrition, not CR
in the traditional sense of CR with adequate nutrition.
Biull Eksp Biol Med 1983 Mar;95(3):108-11
[Ultrastructural changes in the neuropile of the sensorimotor cortex
during long-term protein-calorie deficiency]
[Article in Russian]
Medvedev DI, Babichenko II, Eremina IZ, Kravtsova AI.
The effect of alimentary (protein-caloric) deficiency on the brain
sensomotor cortex of mice was studied during their postnatal
development. It was found that malnutrition of mice from day 10 to day
40 of postnatal period brought about the most remarkable changes in
synaptic junctions located on the dendritic spines. They manifested
destruction of the spine apparatus, reduction of the width of synaptic
slits and of postsynaptic membranes. Dystrophic and destructive
alterations are frequently encountered in dendrites, axon terminals,
and myelinized axons, indicating the reduced compensatory functions
of the CNS.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6403069&dopt=Abstract
Ian Goddard
>What about the rest of the cortex? Please keep us informed.
>Here's an unpleasant thought. Animal studies will not show the
>CR-induced neurological impairment because they have a
>much lower brain-body ratio. Perhaps only humans are
>susceptible to CR brain-rot.
IAN: And maybe CR will cause people to grow
antlers eventually. In the study I just posted
(Dubey et al), cortex measures were positive. If
there was a strong basis for that concern, surely
we would not find the best example of wide-spread
human CR -- the Okinawan population -- linked to
the longest lifespans and low rates of dementia:
http://okinawaprogram.com/images/dem.gif
If CR was linked to "brain rot" that human data
should be the opposite of what it actually is.
michaelprice
>
>> Here's an unpleasant thought. Animal studies will not show the
>> CR-induced neurological impairment because they have a
>> much lower brain-body ratio. Perhaps only humans are
>> susceptible to CR brain-rot.
>
>
> IAN: And maybe CR will cause people to grow
> antlers eventually.
But less likely, since Walford has neurological impairment
not antlers. Another possibility is that Walford is chronically
malnurished. He has never been that keen on supplements.
(Did he skip them in biosphere 2? Would they have been
allowed?)
> In the study I just posted
> (Dubey et al), cortex measures were positive.
The cortex measures did not actually measure synaptic densities,
which may be a better indicator of early decline rather than loss
of behavioural function, which more indicative of end stage, full-blown
neural degeneration. cf. Parkinsons which only become behaviourly
or clinically evident when neuronal loss is quite advanced.
> If there was a strong basis for that concern, surely
> we would not find the best example of wide-spread
> human CR -- the Okinawan population -- linked to
> the longest lifespans and low rates of dementia:
>
> http://okinawaprogram.com/images/dem.gif
>
> If CR was linked to "brain rot" that human data
> should be the opposite of what it actually is.
I note the Okinawan and Japan dementia levels co-incide at 80-84. If the
Okinawans are really age retarded w.r.t the Japanese then this might be seen
as evidence in *favour* of CR induced *relative* neural degeneration.
Perhaps I'm forcing the interpretation a bit here, but even so.... the graph
was not as positive as it might have been.
Cheers,
Michael C Price
Paul
"michaelprice" <michae...@ntlworld.com> wrote in message
news:pcfq8.4473$Np3.6...@news2-win.server.ntlworld.com...
>
> But less likely, since Walford has neurological impairment
> not antlers. Another possibility is that Walford is chronically
> malnurished. He has never been that keen on supplements.
> (Did he skip them in biosphere 2? Would they have been
> allowed?)
If you read page 140 of Walfords book "Maximum Life Span" published in 1983
he says
" Not an exhaustive list, it's part of what I take daily in divided doses:
Vitamin E 600 IU
Selenium 160 mCg
BHT 250 mg
Cysteine 300 mg
Methionine 120 mg
Ascorbyl Palmitate 600 mg
Vitamin C 1000 mg
Bioflavinoids 300 mg "
OK these amount are not in the Pearson & Shaw ingestible league but they
suggest to me that Walford was quite keen on supplements.
Of course I have no way of knowing whether he maintained this programme,
does anyone know otherwise?
Peace & Long Life
Paul
Ian Goddard
>> IAN: And maybe CR will cause people to grow
>> antlers eventually.
>
>But less likely, since Walford has neurological impairment
>not antlers. Another possibility is that Walford is chronically
>malnurished.
IAN: Yes, but I've tentatively viewed Walford's condition
as equivalent to testimonial evidence; ie, the health of
one person doing intervention x is very weak evidence. But
if evidence from CR research lines up with his condition,
as it may well be doing, we have to take notice, as I am.
I recall, but can't remember where I read this, that Walford
for some time practiced a CR regime of fasting one day and
then eating fully the next... that would be like on-and-
off malnutrition. It may have read that in his book.
Alan Pater posted the full fewer-synapses study here:
http://groups.yahoo.com/group/crsociety/message/18596
>> If there was a strong basis for that concern, surely
>> we would not find the best example of wide-spread
>> human CR -- the Okinawan population -- linked to
>> the longest lifespans and low rates of dementia:
>>
>> http://okinawaprogram.com/images/dem.gif
>>
>> If CR was linked to "brain rot" that human data
>> should be the opposite of what it actually is.
>
>I note the Okinawan and Japan dementia levels co-incide at 80-84. If the
>Okinawans are really age retarded w.r.t the Japanese then this might be seen
>as evidence in *favour* of CR induced *relative* neural degeneration.
>Perhaps I'm forcing the interpretation a bit here, but even so.... the graph
>was not as positive as it might have been.
IAN: Despite those factors that might have to do
with record keeping, there appears on average to
be less dementia corresponding to populations
known to consum fewer calorics, which nicely
matches most of available CR-animal research.
Tim
extends lifespan is that it decreases free radical production.
However, research on CR tends to support about every major theory of
aging and their is certainly no dearth of hypotheses on how CR works.
Tim
Ian Goddard
Here's an excellent review by Dean Pomerleau of the
CR study finding reduced synapses in the layer 2 of
sensorimotor cortex (Dean gave permission to post):
-----Original Message-----
From: crsocie...@lists.uchicago.edu On Behalf Of Dean Pomerleau
Sent: Tuesday, April 02, 2002 10:29 AM
To: crso...@lists.uchicago.edu
Subject: CR and Brain Health (was: RE: [CR] Re: CR Research Update)
Ian Goddard posted the abstract to study [1] (thanks Ian!) showing
that CR seems to result in fewer synapses in part of the sensorimotor
cortex, a potential adverse consequence of CR, since this area of the
brain is important for motor/ambulatory functions.
In the full text of the article, the authors speculate that the
reduced number of synapses may be due to the reduced level of IGF-1
(insulin-like growth factor 1) exhibited by CR rodents (and people),
since IGF-1 has been shown to be important for synapse formation and
maintenance.
The authors speculate that starting CR as early as they did (4 months,
which is about equivalent to a 12 year-old person), may have been too
early, and may have interfered with synaptic development/maintenance:
"Although the initial synaptogenesis is virtually complete when
caloric restriction is initiated at 4 months [ref and ref], synaptic
plasticity in the central nervous system continues well after the
initial period of synaptogenesis [ref]. Thus, there may be an early
critical period during which synapses are dependent for their
maintenance on a factor or factors that are down-regulated by caloric
restriction."
So starting CR later, as all of us have, may have spared our synapses
during the important adolescent phase of life.
The authors go on to talk about how unlike IGF-1, other brain-boosting
factors ARE upregulated by CR. Thus, while caloric restriction
decreases IGF-1 levels, it appears to increase BDNF [brain derived
neurotrophic factor] levels.
The author's suggests this dual action of calorie restriction on the
brain may explain some of the contradictions in the literature
regarding the impact of CR on behavior and cognition. The authors
explain that these contradictions include the older finding by
Markowska [3] that CR had no effect [sic] on cognitive or sensorimotor
behavior in the same [sic] strain of rats (Fischer-344 rats) used in
this study [1]. Several things are of interest from the Markowska
study [3], discussed on the list previously. First, unlike what seems
to be implied by the authors of the current study, when they say:
"Markowska estimated the behavioral consequences of life-long caloric
restriction on the same strain of animals as the current study and
suggested that caloric restriction neither provided protection against
age-related deficit in memory nor improved performance on sensorimotor
tasks, both associated with the sensorimotor cortex [3]."
Markowska [3] actually found that CR'ed rats DID do better than AL
rats on sensorimotor tasks throughout their lifetime:
"Although DR rats outperformed AL rats in sensorimotor tasks
throughout the life-span, the slope of the declining function in DR
rats paralleled those of AL rats, suggesting that diet restriction
failed to alter the rate of aging in sensorimotor performance, as
well."
As the above indicates, it was the SLOPE of decline that was similar
between the two groups, indicating that "aging" of the sensorimotor
system was occurring at about the same rate in the two groups. Given
my choice, I'd rather start with the higher performance afforded by CR
and decline from there...
Even more interesting, the strain of rats Markowska used in [3]
(Fisher-344 rats) wasn't EXACTLY the same strain used in this
fewer-synapse study [1] (hybrid Brown Norway?Fischer 344 rats). More
recently, Markowska [4] found that CR in fact DID retard age-related
decline in cognitive and sensorimotor behavior in EXACTLY the same
strain of rats used in this study [1], Brown Norway?Fischer 344 rats.
So despite apparently having fewer synapses in part of the
sensorimotor cortex, rats of this strain subject to CR did BETTER on
sensorimotor and cognitive tasks, and their performance on these tasks
declined MORE SLOWLY with age than AL-fed controls.
The authors attempt to explain these contractions (fewer synapses, but
improved, or at worst neutral cognitive and motor performance) based
on the complicated effects CR on the brain. In particular, they say:
"Thus, it may be that synaptic efficacy is improved in caloric
restricted animals [2] despite the fact that the synapse number is
lower in caloric restricted animals, and the behavioral performance in
these animals is the compromise of these two changes, which explains
lack [sic] of sensorimotor and memory changes."
This would seem to me to be a reasonable conclusion, except that,
contrary to the authors' statement, the compromise seems to come out
in favor of CR, at least in this particular strain of rats. This
apparently beneficial impact of CR on cognition is made all the
stronger by the overwhelming amount of evidence (discussed previously
on the list, and in the introduction to [1]) that CR slows or prevents
important neurodegenerative disorders, including Alzeheimer's,
Huntington's [40] and Parkinson's diseases.
It some ways these finding parallel the apparent contradiction in
CR'ed animals and people regarding white blood cell count and
immunity. Specifically, white blood cell count is suppressed by CR
(normally a sign of a compromised immune system) but CR'ed animals
(and probably people, if anecdotal evidence is to be believed) appear
to have more effective immune systems and succumb to fewer illnesses.
On CR, we do better with less.
--Dean
-----------------------------------------
> [1] Brain Res 2002 Mar 22;931(1):32-40
>
> Caloric restricted male rats demonstrate fewer synapses in layer
> 2 of sensorimotor cortex.
>
> Shi L, Poe BH, Constance Linville M, Sonntag WE, Brunso-Bechtold JK.
>
> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11897086&dopt=Abstract
>
> PMID: 11897086
----------------------------------------
[2] J Neurochem 2000 Jul;75(1):314-20
Beneficial effects of dietary restriction on cerebral cortical
synaptic terminals: preservation of glucose and glutamate transport
and mitochondrial function after exposure to amyloid beta-peptide,
iron, and 3-nitropropionic acid.
Guo Z, Ersoz A, Butterfield DA, Mattson MP.
... Loss of mitochondrial function caused by oxidative and metabolic
insults, as indicated by increased levels of reactive oxygen species
and decreased transmembrane potential, was significantly attenuated in
synaptosomes from rats maintained on DR. ... Collectively, our data
provide the first evidence that DR can alter synaptic homeostasis in a
manner that enhances the ability of synapses to withstand adversity.
PMID: 10854276
----------------------------------------
[3] Neurobiol Aging 1999 Mar-Apr;20(2):177-89
Life-long diet restriction failed to retard cognitive aging in
Fischer-344 rats.
Markowska AL.
... In the present study, the effects of long-term dietary restriction
(60% of ad-libitum calories) on an age-related alteration of memory
and sensorimotor function have been investigated in Fischer 344 male
rats at four different ages: 6 months, 12 months, 18 months, and 24
months... Although DR rats outperformed AL rats in sensorimotor tasks
throughout the life-span, the slope of the declining function in DR
rats paralleled those of AL rats, suggesting that diet restriction
failed to alter the rate of aging in sensorimotor performance, as
well.
PMID: 10537027
---------------------------------------------
[4] Neurobiol Aging 2002 Jan-Feb;23(1):75-86
Retardation of cognitive aging by life-long diet restriction:
implications for genetic variance.
Markowska AL, Savonenko A.
Long-term moderate dietary restriction (DR) has been reported to
extend life spans, delay the onset and decrease the incidence of a
broad spectrum of age-associated diseases; however, its effect on
cognition is still unclear. Our previous results indicated that
long-term DR failed to retard cognitive and psychomotor aging in the
inbred strain, Fischer-344 rats. In the present experiment, an
anti-aging effect of DR on various types of cognitive and sensorimotor
behaviors was found in F1 hybrid Fischer-344 x Brown Norway (F-344xBN)
rats, while no effect of DR was detected in the second parental
inbred strain, Brown-Norway (BN) rats. These findings show that the
lack of an effect of DR on cognitive aging, which was previously found
in Fischer-344 rats, is not a universal phenomenon. Instead, the
effect of DR may depend upon the genetic makeup of the animals. Thus,
a more diverse genetic milieu, such as in hybrid rats, relative to
inbred rats, may increase the susceptibility to an effect of DR on
age-related cognitive decline.
PMID: 11755022
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Ian Goddard
> antlers eventually. In the study I just posted
> (Dubey et al), cortex measures were positive. If
> there was a strong basis for that concern, surely
> we would not find the best example of wide-spread
> human CR -- the Okinawan population -- linked to
> the longest lifespans and low rates of dementia:
>
> http://okinawaprogram.com/images/dem.gif
>
> If CR was linked to "brain rot" that human data
> should be the opposite of what it actually is.
Consistent with the demonstrated neuro-protective effects
of CR in animals and a suggested anti-dementia effect in
humans (see graph above), the following study found that
CR (referred to below as dietary restriction) increased
the proliferation of brain cells in the hippocampus, a
brain region central to memory and that is a primary
target in forms of dementia such as Alzheimer's. Far
from being suspected of "brain rot," the overwhelming
body of evidence points to CR as being neuro-protective.
Also consider that the study by Shi et al did not find
a reduction of neurons (brain cells), only of synapses
between neurons in one region. "Brain rot" would be
brain-cell death leading to brain atrophy. There is no
evidence linking CR to brain rot, and as the following
recent study shows, it has a link to brain growth in
an a brain region central to cognitive performance:
J Neurochem 2002 Feb;80(3):539-47
Dietary restriction enhances neurotrophin expression and neurogenesis
in the hippocampus of adult mice.
Lee J, Seroogy KB, Mattson MP.
Laboratory of Neurosciences, National Institute on Aging Gerontology
Research Center Baltimore, Maryland 21224, USA.
The adult brain contains small populations of neural precursor cells
(NPC) that can give rise to new neurons and glia, and may play
important roles in learning and memory, and recovery from injury.
Growth factors can influence the proliferation, differentiation and
survival of NPC, and may mediate responses of NPC to injury and
environmental stimuli such as enriched environments and physical
activity. We now report that neurotrophin expression and neurogenesis
can be modified by a change in diet. When adult mice are maintained on
a dietary restriction (DR) feeding regimen, numbers of newly generated
cells in the dentate gyrus of the hippocampus are increased,
apparently as the result of increased cell survival. The new cells
exhibit phenotypes of neurons and astrocytes. Levels of expression of
brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are
increased by DR, while levels of expression of high-affinity receptors
for these neurotrophins (trkB and trkC) are unchanged. In addition, DR
increases the ratio of full-length trkB to truncated trkB in the
hippocampus. The ability of a change in diet to stimulate neurotrophin
expression and enhance neurogenesis has important implications for
dietary modification of neuroplasticity and responses of the brain to
injury and disease.
Ian Goddard
IAN: Based on what I've read, there has been and is sufficient
uncertainty about the causal basis of CR-induced life extension
(LE) in animals to undermine the implication I addressed that,
unlike nucleic acids, research into CR as a LE method was not
avoided because it fits with the free-radical theory of aging.
In short, I don't see a basis for the preferential selection of
only those LE modalities that fit into the free-radical paradigm.
Further, as to the other point, it stands to reason that researching
nucleic acids, even if they cannot themselves be patented, would be
a more probable course to discovering patentable products than the
utilization of CR in aging research. Indeed, much of the research
you can find on unpatentable herbs is an effort to find how they
work so as to find patentable mimetic chemicals. Of course now
some CR research is doing that--looking for profitable mimetics.
Apparently some of the LEF-funded research is an effort to find
alternative patentable means to do the same things that CR does.
In sum, as I see it, medical science first looks for what works.
Then it tries to find why x works. Then it tries to find what y
does the same things as x that can be patented. Given that, if
nucleic acids really worked as those two old studies posted
suggest, I would expect to find successful follow-up research.
Given that no such research have been forthcoming, and my brief
searches failed to uncover any, I'm skeptical of nucleic-acid LE.
"To lengthen thy life, lessen thy meals." Benjamin Franklin
http://www.ultrahiq.net/Ubiquity/Winter02/CR.html
michaelprice
> that CR seems to result in fewer synapses in part of the sensorimotor
> cortex, a potential adverse consequence of CR, since this area of the
> brain is important for motor/ambulatory functions.
>
> In the full text of the article, the authors speculate that the
> reduced number of synapses may be due to the reduced level of IGF-1
> (insulin-like growth factor 1) exhibited by CR rodents (and people),
> since IGF-1 has been shown to be important for synapse formation and
> maintenance.
A plausible hypothesis. If CR-induced lower levels of IGF-1 are
responsible for the synaptic atrophy then there is more reason for
thinking this is a CNS wide effect, not just confined to the sensorimotor
cortex.
> The authors speculate that starting CR as early as they did (4
> months, which is about equivalent to a 12 year-old person), may
> have been too early, and may have interfered with synaptic
> development/maintenance:
>
> "Although the initial synaptogenesis is virtually complete when
> caloric restriction is initiated at 4 months [ref and ref], synaptic
> plasticity in the central nervous system continues well after the
> initial period of synaptogenesis [ref]. Thus, there may be an early
> critical period during which synapses are dependent for their
> maintenance on a factor or factors that are down-regulated by caloric
> restriction."
>
> So starting CR later, as all of us have, may have spared our
> synapses during the important adolescent phase of life.
This seems less plausible since synaptogenesis is probably critical
for memory formation and a life-long process (albeit more active
in youngsters). Probably less critical for rodents.than humans!
Cheers,
Michael C Price
michaelprice
> In sum, as I see it, medical science first looks for what works.
> Then it tries to find why x works. Then it tries to find what y
> does the same things as x that can be patented. Given that, if
> nucleic acids really worked as those two old studies posted
> suggest, I would expect to find successful follow-up research.
> Given that no such research have been forthcoming, and my brief
> searches failed to uncover any, I'm skeptical of nucleic-acid LE.
Another reason why the nucleic-acid research was not followed up
may have been the lack of a plausible mechanism. Science does not
readily take on board purely empirically driven hypotheses until a
mechanism is proposed. (e.g. continental drift was not accepted
despite all the paleofossil evidence for decades). In the nucleic acid
case there was no plausible mechanism (this was before Watson &
Crick) to explain the life extension. Ribozymes - enzymes made of
nucleotides instead of aminoacids - were unknown, along
with the nucleotide salvage pathways.
Now, of course, people just say it was a long time ago and they don't
believe it.
Cheers,
Michael C Price
Ian Goddard
>> In the full text of the article, the authors speculate that the
>> reduced number of synapses may be due to the reduced level of IGF-1
>> (insulin-like growth factor 1) exhibited by CR rodents (and people),
>> since IGF-1 has been shown to be important for synapse formation and
>> maintenance.
>
>A plausible hypothesis. If CR-induced lower levels of IGF-1 are
>responsible for the synaptic atrophy then there is more reason for
>thinking this is a CNS wide effect, not just confined to the sensorimotor
>cortex.
IAN: Yet Markowska and Savonenko showed that CR reduced the
decline in cognitive and sensorimotor behavior in the same
breed of mice used by Shi et al. So what the observation of
reduced synapses in layer 2 of the sensorimotor cortex means
is not clear--it could reflect improved signaling efficiency.
Moreover, the fact that the animal data and human data (see
Okinawa) only indicates improved (or at worst no effect on)
CNS measures means that the hypothesis of harm that you are
reaching for is not derived from data regarding behavioral
outcomes of CR diets, indeed, your implied hypothesis stands
contrary to the data. The only thing you have is the example
of balance problems in one individual, Dr Walford. As I've
noted, this is essentially equal to testimonial "evidence."
Are you impressed by ads that say "I took vitamin x and now
I feel great!"? Indeed, most of those pseudoscientific ads
even have more testimonial evidence than one single person.
So the "Walford evidence" is lower than those garbage ads.
While the possible correspondence of Walford's state to the
sensorimotor cortex is reason to take notice, I don't think
it's enough to establish weight of evidence at this point.
Of interest, I found on pages 82 and 83 of the 2000 edition
of Walford's "Beyond The 120 Year Diet" that he gives thumbs
up to CR-fasting regimes that involve "short-term fasts of
one or two days per week." He says: "It's acceptable to cut
caloric intake by frequent fasts, if that's the easiest way
for you to go, as long as the fasts are short, no more than
one or two days." He then goes on to state on page 229 that
he follows a once-a-week day-long fast. Such regimes are
short-term starvation to the body. If there is neurological
risk to CR, I suspect that the practice of frank starvation
even short-term would be the way to maximize any risk factor.
And a day or two to the body is not necessarily "short term."
A lot of essential activities take place over a single day.
"To lengthen thy life, lessen thy meals." Benjamin Franklin
http://www.ultrahiq.net/Ubiquity/Winter02/CR.html
Tim
that research was pretty much ignored by gerontologists till the
1970's. I think any preference for CR exerting its effects, at least
in part, by decreaasing free radical production is that free radicals
are very definitely involved in aging either through random damage,
redox signaling or most likely both. There's a good deal of evidence
that this is at least partly correct. But, CR research can also
support hormonal, glycation and other theories but none of these are
mutually exclusive of the other. As far as nucleic acids are concerned
I don't think the research was given much credence at the time as it
was poorly done. Any effect on lifespan could have been IMO simply
because the pyridines are metabolized into uric acid, a potent
antioxidant.
Tim
michaelprice
--
"Tim" <timo...@my-deja.com> wrote in message
news:6da4c14.02040...@posting.google.com...
> As far as nucleic acids are concerned I don't think the research
> was given much credence at the time as it was poorly done.
Do you have any evidence for that view?
Cheers,
Michael C Price
michaelprice
>
> IAN: Yet Markowska and Savonenko showed that CR reduced the
> decline in cognitive and sensorimotor behavior in the same
> breed of mice used by Shi et al. So what the observation of
> reduced synapses in layer 2 of the sensorimotor cortex means
> is not clear--it could reflect improved signaling efficiency.
Or that the synaptic decline had only reached a subclinical level.
BTW I agree that we can't make do much of the "Walford evidence",
but it definitely something to bear in mind in light of future developments.
Cheers,
Michael C Price
Tim
what I was thinking. So I'll fix it propio motu.
Tim
Ian Goddard
>The CR effect on longevity was discovered by McCay in the 1930's and
>that research was pretty much ignored by gerontologists till the
>1970's. I think any preference for CR exerting its effects, at least
>in part, by decreaasing free radical production is that free radicals
>are very definitely involved in aging either through random damage,
>redox signaling or most likely both. There's a good deal of evidence
>that this is at least partly correct. But, CR research can also
>support hormonal, glycation and other theories but none of these are
>mutually exclusive of the other.
IAN: McCay's findings were not seen as discovering a method
of anti-aging. It was assumed that what was happening with
life-long CR was that by delaying the onset of puberty, all
the subsequent phases of life were delayed, including death.
It was not until Weindruch & Walford (1982), who showed that
adult-onset CR could also extend maximum lifespan, that it
became clear that there was a specific anti-aging effect.
It was therefore only at that point that CR would and did
become a serious part of gerontological research. Moreover,
at that point there was no specific red flag indicating CR
was a part of the free-radical theory of aging. So again, I
don't see a basis for the claim that research into nucleic
acids was avoided due to no link to free-radical pathology,
since research into CR wasn't avoided despite the fact that
there was no initial clear link to the free-radical theory.
But I'm also not saying there's nothing to nucleic acids,
just that Mike needs to provide a higher level of evidence
before he can refute the statement he initially claimed to.
"To lengthen thy life, lessen thy meals." Ben Franklin
http://www.ultrahiq.net/Ubiquity/Winter02/CR.html
Tim
longevity.
The fact that even the researchers themselves didn't follow up the
research nor did anyone else. If I remember correctly I think it was
Hans Kugler that did a pilot study (which of course was never
published) with a small number of animals that showed a tremendous
increase in longevity and never attempted to repeat it. I recall a
general disdain by more reputable researchers. I think you can and
probably should lump this in with Gerovital, sheep embryonic cells,or
Gary Evans pilot study with chromium picolinate showing a (about)
40%increase in lifespan (which of course was reported to the press but
never published in a peer reviewed journal and he never attempted to
duplicate) of course he owned the patent and the published studies on
increases in muscle to fat ratio and insulin sensitivity (except in
type II diabetics) couldn't be replicated by anyone else.
Tim
Thomas Carter
Hi, Ian, Michael,
There is a very clear link between nucleic acid supplementation and
the free radical theory due to the fact that an excess of nucleotides
degrade to uric acid, the human's major extra cellular antioxidant.
Thomas
michaelprice
--
"Tim" <timo...@my-deja.com> wrote in message
news:6da4c14.02040...@posting.google.com...
> Probably a lack of any credible way in which it could increase
> longevity.
> The fact that even the researchers themselves didn't follow up the
> research nor did anyone else. If I remember correctly I think it was
> Hans Kugler that did a pilot study (which of course was never
> published) with a small number of animals that showed a tremendous
> increase in longevity and never attempted to repeat it. I recall a
> general disdain by more reputable researchers. I think you can and
> probably should lump this in with Gerovital, sheep embryonic cells,or
> Gary Evans pilot study with chromium picolinate showing a (about)
> 40%increase in lifespan (which of course was reported to the press but
> never published in a peer reviewed journal
A half-truth. The experiment was reported in a peer-reviewed journal.
See "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
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.
"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.
Cheers,
Michael C Price
michaelprice
Ditto me for CR
> just that Mike needs to provide a higher level of evidence
> before he can refute the statement he initially claimed to.
The statement I refuted was:
> Caloric restriction (CR) remains the only nongenetic intervention
> that reproducibly extends mean and maximal life span in short-lived
> mammalian species.
I said:
"Not so. Wrong on both counts. Nucleic acid enriched diets have
reproducibly extended mean and maximum lifespan in mice.
First done by Robertson, repeated by Gardner. Basic difference
was Gardner started on adult mice and lowered the dosage."
And I gave refs.
Now Ian (and others) may chose not to believe the work was valid,
but that is (still) unsubstantiated opinion.
I note, BTW, that Tim's position seems inconsistent. He say he doesn't
believe the RNA LE is valid, and then says it might be due to uric acid(*).
?????
* = which it might be of course, although I doubt it.
Cheers,
Michael C Price
michaelprice
> Gary Evans pilot study with chromium picolinate showing a (about)
> 40%increase in lifespan (which of course was reported to the press but
> never published in a peer reviewed journal and he never attempted to
> duplicate) of course he owned the patent and the published studies on
> increases in muscle to fat ratio and insulin sensitivity (except in
> type II diabetics) couldn't be replicated by anyone else.
They've been duplicated on pigs:
J Anim Sci 1997 Oct;75(10):2661-71 Related Articles, Books, LinkOut
Efficacy of chromium picolinate and chromium chloride as potential carcass
modifiers in swine.
Mooney KW, Cromwell GL.
Department of Animal Sciences, University of Kentucky, Lexington 40546, USA.
We conducted two experiments to evaluate the effects of chromium picolinate
and chromium chloride (CrCl3) on growth performance, carcass composition,
percentages and accretion rates of carcass tissues and chemical components,
and blood metabolites in pigs. In Exp. 1, 35 individually penned pigs were
fed a fortified, corn-soybean meal basal diet (.95% lysine) supplemented
with 0, 200, or 400 micrograms/kg of Cr from chromium picolinate or 5,000 or
25,000 micrograms/ kg of Cr from CrCl3. Each diet was fed to seven pigs for
35 d (19.6 to 43.2 kg BW). Addition of 200 micrograms/kg of Cr from chromium
picolinate increased ADG (P < .07) and ADFI (P < .03) but did not affect
feed:gain ratio. Backfat measurements and longissimus muscle area were not
affected by either source of Cr. The percentages of muscle, fat, bone, and
skin from the right ham and the percentages of water, protein, lipid, and
ash from the left carcass were not significantly altered by Cr. The addition
of 200 micrograms/kg Cr from chromium picolinate increased (P < .07) the
accretion rate of lipid in the carcass. In Exp. 2, 42 individually penned
pigs (three from each of 14 litters) were fed a fortified, corn-soybean meal
basal diet (.95% lysine from 19 to 55 kg; .80% lysine from 55 to 109 kg)
without or with 200 micrograms/kg of Cr from chromium picolinate or 5,000
micrograms/kg of Cr from CrCl3. Dietary Cr addition had no effect on the
performance or backfat measurements of the pigs; however, both sources of Cr
increased (P < .07) longissimus muscle area. The percentages and accretion
rates of muscle tissue were increased (P < .001) and the percentages of fat
tissue were decreased (P < .001) in pigs fed Cr, with chromium picolinate
being more effective than CrCl3 (P < .05). The percentages (P < .01) and
accretion rates (P < .07) of carcass protein were increased and the
percentages and accretion rates of carcass lipid were decreased (P < .04) in
pigs fed Cr. No changes in blood metabolites occurred as a result of
supplemental Cr in either experiment. These results suggest that chromium
picolinate is more effective than CrCl3 and that Cr must be supplemented
throughout the growing-finishing period to improve the carcass composition.
PMID: 9331868 [PubMed - indexed for MEDLINE]
Cheers,
Michael C Price
michaelprice
Ditto for me on CR
> just that Mike needs to provide a higher level of evidence
> before he can refute the statement he initially claimed to.
The statement I refuted was:
> Caloric restriction (CR) remains the only nongenetic intervention
> that reproducibly extends mean and maximal life span in short-lived
> mammalian species.
when I said:
"Not so. Wrong on both counts. Nucleic acid enriched diets
have reproducibly extended mean and maximum lifespan in mice.
First done by Robertson, repeated by Gardner. Basic difference
was Gardner started on adult mice and lowered the dosage."
And I gave refs.
Now Ian (and others) may chose not to believe the works were
valid, but that is (still) an unsubstantiated opinion.
I note, BTW, that Tim's position seems inconsistent. He say he doesn't
believe the RNA LE is valid, and then says it might be due to uric acid(*).
?????
* = which it might be of course, although I doubt it since rodents further
degrade uric acid to allantoin.
Cheers,
Michael C Price
michaelprice
> Hi, Ian, Michael,
> There is a very clear link between nucleic acid supplementation
> and the free radical theory due to the fact that an excess of
> nucleotides degrade to uric acid, the human's major extra cellular
> antioxidant.
> Thomas
Is that true for rodents? Since rodents further degrade uric acid
to allantoin I doubt that the life extension found with nucleic acid
supplementation is due to free uric acid.
Cheers,
Michael C Price
michaelprice
> 40%increase in lifespan (which of course was reported to the press but
> never published in a peer reviewed journal and he never attempted to
> duplicate)
The full story is: The experiment was reported in a peer-reviewed journal.
See "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
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.
The lifespan result was reported in:
"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.
which may or may not be peer-reviewed, I don't know.
So we see that whilst the lifespan result may or may not have been published
in the peer-reviewed literature the experiment's metholology definitely has.
And how hard is it to additionally measure lifespan? All you need is
patience and lab space.
> of course he owned the patent and the published studies on
> increases in muscle to fat ratio and insulin sensitivity (except in
> type II diabetics) couldn't be replicated by anyone else.
They've been duplicated on pigs:
Ian Goddard
>> just that Mike needs to provide a higher level of evidence
>> before he can refute the statement he initially claimed to.
>
>The statement I refuted was:
>
>> Caloric restriction (CR) remains the only nongenetic intervention
>> that reproducibly extends mean and maximal life span in short-lived
>> mammalian species.
>
>when I said:
>
>"Not so. Wrong on both counts. Nucleic acid enriched diets
>have reproducibly extended mean and maximum lifespan in mice.
>First done by Robertson, repeated by Gardner. Basic difference
>was Gardner started on adult mice and lowered the dosage."
>
>And I gave refs.
>Now Ian (and others) may chose not to believe the works were
>valid, but that is (still) an unsubstantiated opinion.
IAN: Mike, I've already noted that two studies is merely
the most minor suggestion of reproducibility. For you to
refute the statement cited above you have to show a level
of reproducibility approaching or comparable to what has
been established for CR. Two studies is not even close.
They constitute only one single instance of replication.
It's something to wonder about and look into, but not
to hold up as another confirmed means of LE in animals.
Max Watt
But what if the amount of uric acid overloads the enzyme responsible
for the conversion to alantoic, as seems likely? Then the uric acid
mechanism seems possible.
Tim
the first abstract you cite only mentions decreasing glycation of the
rats hemoglobin, and could be considered self-serving as it is
compared with a competing supplement. If I recall correctly the
lifespan study was a pilot study with a small number of rats (which
normally wouldn't be published anyway) and I couldn't locate the
article an pubmed. But no one else has been able to replicate any of
his other research for the most part in nondiabetic humans. As with
the case of GH3 people selling it reported a lot of benefits,
including an increase in lifespan, that others couldn't replicate. It
may well do something (like be an MAO inhibitor, which I would concur
with based on my own subjective experience). I tend to be extremely
vexed by a lot of the crap that is pushed as anti-aging by some I
suspect less than well intentioned people for their own benefit. Some
of it may well work, I generally view things in probabilities, and
without any real hard evidence I would generally attribute to them a
low probability of any utility.
Regards,
Tim
Tim
as well. Nucleic acid rich foods definitely do increase uric acid and
are a risk factor for gout.
Tim
J cash
pure form, only desire a drop of sweet liquid to content itself? " --
Thoreau, from Walden
michaelprice <michae...@ntlworld.com> wrote in message
news:fvSq8.5250$Ll2.4...@news6-win.server.ntlworld.com...
Rich Andrews
news:FrGr8.23193$9N1.4...@typhoon.nyc.rr.com:
> "Does not a butterfly begin as a gluttonous caterpillar, but then, in
> its pure form, only desire a drop of sweet liquid to content itself? "
> -- Thoreau, from Walden
>
>
Is not a diamond but a bit of coal?
r
--
"I will not be pushed, filed, stamped, indexed, briefed, de-briefed, or
numbered...My life is my own."
"I am not a number. I am a free man."
No. 6
michaelprice
> unlike birds, prior to excretion as well.
My textbooks say endpoint breakdown and excretion
product is:
Uric acid for birds, some reptiles, primates (including humans)
Allantoin for most mammals, turtles, some insects, gastropods
Allantoate for some bony (teleost?) fishes
Urea for most (cartilaginous?) fishes, amphibians, freshwater mollusks
Ammonia for plants, crustaceans, many marine invertebrates
Cheers,
Michael C Price
michaelprice
> mentions decreasing glycation of the rats hemoglobin,
and lower plasma glucose levels, so a reasonable inference
is a lower glycation rate generally.
> and could be considered self-serving as it is compared
> with a competing supplement.
Not "self-serving". The abstract also reported a positive effect
with chromium-dinicotinate on adipose cells.
> If I recall correctly the lifespan study
Just to clarify: the same study
> was a pilot study with a small number of rats
How many rats? Numbers please.
> (which normally wouldn't be published anyway) and I
> couldn't locate the article an pubmed. But no one else
> has been able to replicate any of his other research for
> the most part in nondiabetic humans.
Mostly because (I suspect) it has been tested on young healthy
non-obese students, whom we would not expect to be diabetic or
even pre-diabetic.
[tangent on GH3 deleted]
> Some of it may well work, I generally view things in probabilities,
Me too. The only way to progress.
> and without any real hard evidence I would generally attribute
> to them a low probability of any utility.
The way I do the calculation is a bit different. Taking chromium picolinate
as my example, I note:
Proven benefit to diabetics (hence probable benefit to pre-diabetics)
Passed the Ames test okay, even at astronomical doses
Side effects: rarely a transient rash and dizziness
Diabetes is very widespread & most humans become pre-diabetic as they age
Debatable value as a life extender - may considerably extend lifespan, or
may not.
Which gives me (at age 42) a positive Bayesian expectation of utility.
Cheers,
Michael C Price
michaelprice
"J cash" <jc...@nyc.rr.com> wrote in message
news:FrGr8.23193$9N1.4...@typhoon.nyc.rr.com...
Steve Harris
"michaelprice" <michae...@ntlworld.com> wrote in message news:5MKr8.2562
> The way I do the calculation is a bit different. Taking chromium
picolinate
> as my example, I note:
>
> Proven benefit to diabetics (hence probable benefit to pre-diabetics)
> Passed the Ames test okay, even at astronomical doses
Yep, we saw NO life span toxity signs at 100 ppm-- somewhere between 100 and
10 times average human doses.
> Side effects: rarely a transient rash and dizziness
As compared to placebo?
Like CoQ10 and folate, I can at least guess that even fairly large amounts
of chromium picolinate are safe.
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]."
Steve Harris
> pure form, only desire a drop of sweet liquid to content itself? " --
> Thoreau, from Walden
Probably writen after Thoreau started wasting away from consumption.
Anyway, he didn't know the half of it. Some moths are born with a gut, but
no probosci, so they can't eat, even if they do have the desire. I think of
the Harlan Ellison story: "I Have no Mouth, and I Must Scream." In this
case, "I Have No Mouthparts, and I Must Suck."
We could make it the special horror story of the American Democratic Party.
Steve Harris
"Ian Goddard" <igod...@erols.mom> wrote in message
> IAN: McCay's findings were not seen as discovering a method
> of anti-aging. It was assumed that what was happening with
> life-long CR was that by delaying the onset of puberty, all
> the subsequent phases of life were delayed, including death.
Not everybody assumed that. Even McCay, if I am to credit hearsay. I once,
10 years ago at UCLA, heard a lecture by gerontologist James E. Birrin, in
which he mentioned that he's served in WWII aboard a destroyer with the very
same Clive McCay, and McCay spent a lot of time telling people they would do
better to eat less if they wanted to live longer!
That's a hell of a good story, if true.
Tim
Most of our nitrogenous waste from protein catabolism is excreted as
urea whereas birds excrete theirs as uric acid.
Tim
Tim
elderly, obese, in cats, dogs even pigs on insulin and glucose levels
fat loss or muscle gain. Evans is at least a good salesman as he was
able to market chromium picolinate to every niche of the supplement
market.
Tim
Tim
You tested a number of supplements for their effects on lifespan didn't you?
Did you test chromium picolinate? If so what result did you get.
Tim
Steve Harris
No effect of Cr-picolinate at all (vs. control) on life span or weight at
100 ppm Cr+3 (as the picolinate from Nutrition 21) by weight in dry diet,
from weaning till death. Nor brewers' yeast (something like 5% of diet).
Same results for folate at 1000 ppm. And nothing for several doses of
WR-2721, nowadays a.k.a. ethiophos/Amifostine. I really should publish this
somewhere, even in abbreviated form.
michaelprice
news:l$xl3wj2...@newssvr.manx.net...> news:pcfq8.4473$Np3.6...@news2-win.server.ntlworld.com...
> >
> > But less likely, since Walford has neurological impairment
> > not antlers. Another possibility is that Walford is chronically
> > malnurished. He has never been that keen on supplements.
> > (Did he skip them in biosphere 2? Would they have been
> > allowed?)
>
> If you read page 140 of Walfords book "Maximum Life Span" published in
1983
> he says
>
> " Not an exhaustive list, it's part of what I take daily in divided doses:
>
> Vitamin E 600 IU
> Selenium 160 mCg
> BHT 250 mg
> Cysteine 300 mg
> Methionine 120 mg
> Ascorbyl Palmitate 600 mg
> Vitamin C 1000 mg
> Bioflavinoids 300 mg "
>
What, no B-vitamins? Very couragous....
Cheers,
Michael C Price
Paul
Well there may have been B Vitamins, he does say "Not an exhaustive list".
I only learned today that Kathy Keeton, co founder of Longevity magazine,
died in 1997 of cancer. Sad and ironic.
Peace & Long Life
Paul
>
michaelprice
news:6da4c14.02040...@posting.google.com...
> The majority of the studies by others [than Evans]
> show no effect whether in the elderly, obese, in cats,
> dogs even pigs on insulin and glucose levels fat loss
> or muscle gain.
Let's examine this claim:
RA Anderson is a repected researcher - probably the leading
researcher - on chromium. A search on pubmed for
"chromium picolinate" and "anderson"
yields 8 hits.
6 demonstrate positive effects of chromium picolinate
1 demonstrates lack of toxicity (#5)
1 is a null result (#2).
That sounds likes 6:1 in favour of CrPic.
> Evans is at least a good salesman as he was able to market
> chromium picolinate to every niche of the supplement
> market.
Nice soundbite. Shame about the facts.
Cheers,
Michael C Price
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]
Rich Andrews
It is also ironic that Linus Pauling, a proponent of ingesting mega-doses
of Vit C to prevent cancer, died of cancer.
r
John VanSickle
>
> Anyway, he didn't know the half of it. Some moths are born with a gut,
> but no probosci, so they can't eat, even if they do have the desire.
> I think of the Harlan Ellison story: "I Have no Mouth, and I Must
> Scream." In this case, "I Have No Mouthparts, and I Must Suck."
>
> We could make it the special horror story of the American Democratic
> Party.
That would be imprecise. The Democrats, unfortunately, do have mouth
parts, very noisy ones at that. But they still suck.
--
"Don't talk to me about naval tradition. It's nothing but rum, sodomy,
and the lash." -- Winston Churchill
Paul
> >> > Ascorbyl Palmitate 600 mg
> >> > Vitamin C 1000 mg
> >> > Bioflavinoids 300 mg "
> >> >
> >> What, no B-vitamins? Very couragous....
> >> Cheers,
> >> Michael C Price
> >
> >
> > Well there may have been B Vitamins, he does say "Not an exhaustive
> > list".
> >
> > I only learned today that Kathy Keeton, co founder of Longevity
> > magazine, died in 1997 of cancer. Sad and ironic.
> >
> > Peace & Long Life
> >
> > Paul
> >>
> >
> >
> >
>
> It is also ironic that Linus Pauling, a proponent of ingesting mega-doses
> of Vit C to prevent cancer, died of cancer.
>
made it to her mid sixties.
In truth 94 isn't long enough for me, but I'll take over 60 every time :-)
michaelprice
>>> magazine, died in 1997 of cancer. Sad and ironic.
>>
>> of Vit C to prevent cancer, died of cancer.
>>
> Yes indeed, But Linus was about 94 years of age, I doubt if Kathy Keeton
> made it to her mid sixties.
Correct. b1939 - d1997. Didn't even make 60!
> In truth 94 isn't long enough for me, but I'll take over 60 every time :-)
>
> Peace & Long Life
>
> Paul
>
Cheers,
Michael C Price
Rich Andrews
Death can't come soon enough for those in chronic, intractable pain. It is
all a matter of perspective.