Oral Glycotoxins Determine the Effects of Calorie Restriction on Oxidant Stress, Age-Related Diseases, and Lifespan
timo...@my-deja.com
Oral Glycotoxins Determine the Effects of Calorie Restriction on
Oxidant Stress, Age-Related Diseases, and Lifespan.Cai W, He JC, Zhu
L, Chen X, Zheng F, Striker GE, Vlassara H.
From the Department of Geriatrics,* Division of Experimental Diabetes
and Aging, and the Department of Medicine, Division of Nephrology,
Mount Sinai School of Medicine, New York, New York; and the
Departments of Medicine and Surgery, Miller School of Medicine,
University of Miami, Miami, Florida.
We previously showed that the content of advanced glycation end
products (AGEs) in the diet correlates with serum AGE levels, oxidant
stress (OS), organ dysfunction, and lifespan. We now show that the
addition of a chemically defined AGE (methyl-glyoxal-BSA) to low-AGE
mouse chow increased serum levels of AGEs and OS, demonstrating that
dietary AGEs are oxidants that can induce systemic OS. OS predisposes
to the development of cardiovascular and chronic kidney diseases;
calorie restriction (CR) is the most studied means to decrease OS,
increase longevity, and reduce OS-related organ damage in mammals.
Because reduction of food intake also decreases oxidant AGE s intake,
we asked whether the beneficial effects of CR in mammals are related
to the restriction of oxidants or energy. Pair-fed mice were provided
either a CR diet or a high-AGE CR diet in which AGEs were elevated by
brief heat treatment (CR-high). Old CR-high mice developed high levels
of 8-isoprostanes, AGEs, RAGE, and p66(shc), coupled with low AGER1
and GSH/GSSG levels, insulin resistance, marked myocardial and renal
fibrosis, and shortened lifespan. In contrast, old CR mice had low OS,
p66(shc), RAGE, and AGE levels, but high AGER1 levels, coupled with
longer lifespan. Therefore, the beneficial effects of a CR diet may be
partly related to reduced oxidant intake, a principal determinant of
oxidant status in aging mice, rather than decreased energy intake.
PMID: 18599606 [PubMed - as supplied by publisher]
jc101
> Am J Pathol. 2008 Jul 3. [Epub ahead of print] Links
> Oral Glycotoxins Determine the Effects of Calorie Restriction on
> Oxidant Stress, Age-Related Diseases, and Lifespan.Cai W, He JC, Zhu
> L, Chen X, Zheng F, Striker GE, Vlassara H.
> From the Department of Geriatrics,* Division of Experimental Diabetes
> and Aging, and the Department of Medicine, Division of Nephrology,
> Mount Sinai School of Medicine, New York, New York; and the
> Departments of Medicine and Surgery, Miller School of Medicine,
> University of Miami, Miami, Florida.
>
> We previously showed that the content of advanced glycation end
> products (AGEs) in the diet correlates with serum AGE levels, oxidant
> stress (OS), organ dysfunction, and lifespan. We now show that the
> addition of a chemically defined AGE (methyl-glyoxal-BSA) to low-AGE
> mouse chow increased serum levels of AGEs and OS, demonstrating that
> dietary AGEs are oxidants that can induce systemic OS. OS predisposes
> to the development of cardiovascular and chronic kidney diseases;
> calorie restriction (CR) is the most studied means to decrease OS,
> increase longevity, and reduce OS-related organ damage in mammals.
> we asked whether the beneficial effects of CR in mammals are related
> to the restriction of oxidants or energy. Pair-fed mice were provided
> either a CR diet or a high-AGE CR diet in which AGEs were elevated by
> brief heat treatment (CR-high). Old CR-high mice developed high levels
> of 8-isoprostanes, AGEs, RAGE, and p66(shc), coupled with low AGER1
> and GSH/GSSG levels, insulin resistance, marked myocardial and renal
> fibrosis, and shortened lifespan. In contrast, old CR mice had low OS,
> p66(shc), RAGE, and AGE levels, but high AGER1 levels, coupled with
> longer lifespan. Therefore, the beneficial effects of a CR diet may be
> partly related to reduced oxidant intake, a principal determinant of
> oxidant status in aging mice, rather than decreased energy intake.
>
> PMID: 18599606 [PubMed - as supplied by publisher]
This is a very important study, and provides nails in the CRON coffin.
From Fig. 10 - Survival, Chronic study : " Lifespan of Low and CR
groups was significantly longer than in Reg (P < 0.004) and CR-high
groups (P < 0.0001). Lifespan in CR-high mice was significantly
shorter than in Reg (P < 0.02), CR (P < 0.001)"
The mice with the regular diet (Reg) lived longer than the calorie
restricted (-40% calorie) mice that had AGEs added to their chow (CR-
high). I have questioned the author by email as to whether the Low
group (same calories as Reg, but low in AGEs) had equal lifespan as
the CR group (as the caption to Figure 10 suggests), and will report
if there is an answer forthcoming.
So, it's the stove causing the problem, not that one is eating the
right amount of food for a healthy weight (BMI 24 - lowest mortality).
So, cook fats and protein as little as possible and at as low a temp
as possible, and maintain BMI 24. Use Kremezin (AGEs adsorber) after
meals with cooked fats and proteins. Bid adieu to calorie restriction.
Or one might continue the hypoglycemia of Faith Based Moderate Calorie
Restriction (FBMCR) and join the Motor Neuron Destruction Lab
research, which is currently soliciting participants.
JLC
timo...@my-deja.com
ingestion of glycotoxins. Here is a study published last year
regarding serum glucose levels and longevity. Note one of the authors
Vincent Monnier is one of the minds behind the glycation theory of
longevity. I'll also post thiis separately. This suggests that dietary
modifications such as a more vegetarian diet or raw food may be
useful. I scanned the abstracts on glycotoxins over the past couple
months and research in this area has taken off.
J Gerontol A Biol Sci Med Sci. 2007 Oct;62(10):1059-70. Links
Plasma glucose and the action of calorie restriction on aging.McCarter
R, Mejia W, Ikeno Y, Monnier V, Kewitt K, Gibbs M, McMahan A, Strong
R.
The Pennsylvania State University, Center for Developmental and Health
Genetics, Gardner House, University Park, PA 16802, USA. rj...@psu.edu
We tested the hypothesis that retardation of aging by caloric
restriction is due in part to decreased levels of plasma glucose over
the life span. Male C57BL/6 mice expressing a human GLUT4 minigene
(transgenic [TG] mice) and their nontransgenic littermates (NTG mice)
were maintained under specific pathogen-free conditions. Mice were fed
ad libitum (A mice) or 40% less than ad libitum (R mice) from age 6
weeks. Over the life span there were three different levels of plasma
glucose, with NTGA mice having the highest daily levels, TGR mice the
lowest daily values, and TGA and NTGR mice having similar levels
intermediate between these values. Despite differences in plasma
glucose, the differences measured in longevity (50% and 10% survival),
physiology and tissue pathology were associated with diet rather than
with levels of plasma glucose. We conclude that decreased plasma
glucose over the life span is not an important factor in the action of
calorie restriction on aging processes.
PMID: 17921417 [PubMed - indexed for MEDLINE]
jc101
Good point, low blood sugars are not involved in longevity, but they
may well be involved in the rate of motor neuron disease.
Vlassara's body of work shows that it is the heating of fats and
proteins that is most harmful, with higher heat and longer cooking
most detrimental, compared to that of starch based foods.
JLC
François Rose
> Am J Pathol. 2008 Jul 3. [Epub ahead of print] Links
> Oral Glycotoxins Determine the Effects of Calorie Restriction on
> Oxidant Stress, Age-Related Diseases, and Lifespan.Cai W, He JC, Zhu
> L, Chen X, Zheng F, Striker GE, Vlassara H.
> From the Department of Geriatrics,* Division of Experimental Diabetes
> and Aging, and the Department of Medicine, Division of Nephrology,
> Mount Sinai School of Medicine, New York, New York; and the
> Departments of Medicine and Surgery, Miller School of Medicine,
> University of Miami, Miami, Florida.
>
> We previously showed that the content of advanced glycation end
> products (AGEs) in the diet correlates with serum AGE levels, oxidant
> stress (OS), organ dysfunction, and lifespan. We now show that the
> addition of a chemically defined AGE (methyl-glyoxal-BSA) to low-AGE
> mouse chow increased serum levels of AGEs and OS, demonstrating that
> dietary AGEs are oxidants that can induce systemic OS. OS predisposes
> to the development of cardiovascular and chronic kidney diseases;
> calorie restriction (CR) is the most studied means to decrease OS,
> increase longevity, and reduce OS-related organ damage in mammals.
> we asked whether the beneficial effects of CR in mammals are related
> to the restriction of oxidants or energy. Pair-fed mice were provided
> either a CR diet or a high-AGE CR diet in which AGEs were elevated by
> brief heat treatment (CR-high). Old CR-high mice developed high levels
> of 8-isoprostanes, AGEs, RAGE, and p66(shc), coupled with low AGER1
> and GSH/GSSG levels, insulin resistance, marked myocardial and renal
> fibrosis, and shortened lifespan. In contrast, old CR mice had low OS,
> p66(shc), RAGE, and AGE levels, but high AGER1 levels, coupled with
> longer lifespan. Therefore, the beneficial effects of a CR diet may be
> partly related to reduced oxidant intake, a principal determinant of
> oxidant status in aging mice, rather than decreased energy intake.
>
> PMID: 18599606 [PubMed - as supplied by publisher]
About this study,
if anyone has a copy of the full text, I'd be very interested
François Rose
François Rose
>
> - Show quoted text -
I have been quite enthusiastic about Vlassara's work for more than a
year : that's why I was interested by Thomas 's post here http://tinyurl.com/5k7549
I understand what Thomas means when he says that Helen Vlassara "has
been for decades dreaming up experiments that are designed to
prove her point."
She takes three groups: a control group, a CR group and a CR group
with a higher load of dietary AGE and she proves that this last group
has a lower lifespan than the control group.
Strangly, she had done tests with five groups (control, CR, CR with
high AGE diet, low AGE diet, low AGE diet + a specific AGE )
and life comparison only with three groups
So what she would have to do (and what she refuses to do or maybe
refuses to publish) is the lifespan comparison between the group with
low AGE and CR group. And if there would be something interesting
there, she would have to add another group (CR with low AGE).
So I follow Carter's opinion about this study here which is an
attempt for Helen Vlassara to link AGE issues with the CR life
extension effects because it is very easy to shorten lifespan (what
did Vlassara in this study) and the tough part is the contrary (where
she did nothing).
So the life extending effect of a low AGE diet has yet to be proved
and Thomas 's remarks about the unnecessity of changing diet seems
reasonable to me actually. (I've pasted below his remarks)
> There are neither theoretical nor observational reasons to be
> concerned about AGEs in the diet. Most especially since they
> frequently are seen in food that is not healthy for other reasons, and
> is usually avoided by the prudent dieter.
> Thomas
François Rose
jc101
>
> - Show quoted text -
Vlassara has shown that the Low AGEs Full Calorie group (Low) had the
same lifespan as the Calorie Restricted group (CR) since both groups
had the same p value in comparison to the regularly fed group (Reg).
In addition, both Low and CR groups had much more highly significant
results on lifespan compared to the CR group with AGEs added (CR-
high).
From the caption on figure 10 "Lifespan of Low and CR groups was
significantly
longer than in Reg (P < 0.004) and CR-high groups (P < 0.0001)."
I have written to 3 authors for these results, but haven't gotten
them, so will start trying to phone.
The fact that CR and Low groups have equal P values means that they
are the same when compared to the Reg group.
Which means that it is the amount of cooking that is detrimental, not
the amount of calories in normal weight individuals.
But then dysorexics would lose the ghrelin buzz if they ate enough
food.
JLC
François Rose
>
> - Show quoted text -
It appears from the full text that the lifespan has been studied for
only three groups (control, CR, CR+high AGE) and there was no lifespan
study for the group with low AGE diet
from the full text
"CR Diets: Long-Term Studies
C57BL/6 mice (n 66, male, 4 months of age) from the
National Institutes on Aging CR colonies were individually
caged and provided free access to water. Mice were
assigned to one of three diets (n 22 per group): A) a
modified version of NIH-31 calorie-deficient (40% calorie
reduction) diet, which was balanced in minerals and
vitamins (CR)1,2; B) the same CR diet, in which the content
of AGEs was increased by extending heat exposure
(by 15 minutes. at 120°C) (CR-high); and C) The NIH-31
open formula diet (Reg) (Harlan Teklad, Madison, WI)
(Tables 1 and 2). Diets were purchased in small amounts
( 5 kg) and kept at 4°C. Food consumption was monitored
daily for the first 4 weeks, and weekly thereafter
(Table 2). After establishing the daily intake in the CR and
Reg mice, the CR and CR-high were pair-fed. Food was
completely consumed by the mice between feedings
throughout the study. Body weight was monitored biweekly
during the first 3 months and then monthly. These
mice were used for survival curves."
The conclusions about lifespan indicate also that the lifespan
has been studied for only three groups (control, CR, CR+high AGE)
and there was no lifespan study for the group with low AGE diet :
From the full text:
"Survival
Lifespan in CR mice was longer (median and maximal
survival 13.2% and 6%, respectively) than in Reg or
CR-high mice (P 0.001) (Figure 10 and Table 4). In
addition, survival in CR-high mice was shorter than in Reg
(P 0.02) mice. At the median survival of CR-high mice,
65% of CR mice were alive, and at the maximal survival
level of CR-high mice, 30% of CR mice were still alive
(Figure 10 and Table 4)."
The figue 10 also shows curves regarding only three groups (control,
CR,
CR+high AGE)
and not for the group with low AGE diet
So the caption of figure 10:"Figure 10. Survival, chronic study.
Kaplan-Meier survival curves in Reg mice
(open squares), CR mice (filled triangles), and CR-high mice (filled
circles) (n 22 per group). Lifespan of Low and CR groups was
significantly
longer than in Reg (P 0.004) and CR-high groups (P 0.0001).
Lifespan in
CR-high mice was significantly shorter than in Reg (P 0.02), CR (P
0.001). Differences between the curves were estimated by the log rank
test
(see Table 3 for detailed analyses)."
(where the low group appears !!) is either a careless mistake or a
Freudian slip (indicating what Vlassara would want to see true but
can't
prove) since the very authors
tell that there is no lifespan study for the low group (what I regret
since this lack takes off all value to this study))
So Vlassara is wrong when she states in her abstract: "the beneficial
effects of a CR diet may be
partly related to reduced oxidant intake, a principal determinant of
oxidant status in aging mice, rather than decreased energy intake. "
The only thing she has proved is : "the beneficial effects of a CR
diet can be reduced and even cancelled by adding a high AGE dietary
load".
The only thing she has achieved is reducing the beneficial effects of
CR diet. What 's the point? What she has to do is to extend life span.
I consider as an intellectual dishonesty to mix up lab tests between
5
groups and lifespan between 3 out of these 5 groups in order to infer
lifespan conclusions about the 5 groups; this is why I think that
Thomas
Carter could be right in his post http://tinyurl.com/5k7549 and that
this practice relates more Vlassara to a huckster than to a scientist
and I will, in the future, look very carefully (and more than I did)
when I read an article written by Vlassara.
So I confirm what I said earlier:
> So what she would have to do (and what she refuses to do or maybe
> refuses to publish) is the lifespan comparison between the group with
> low AGE and CR group. And if there would be something interesting
> there, she would have to add another group (CR with low AGE).
>
> So I follow Carter's opinion about this study here which is an
> attempt for Helen Vlassara to link AGE issues with the CR life
> extension effects because it is very easy to shorten lifespan (what
> did Vlassara in this study) and the tough part is the contrary (where
> she did nothing).
>
> So the life extending effect of a low AGE diet has yet to be proved
> and Thomas 's remarks about the unnecessity of changing diet seems
> reasonable to me actually. (I've pasted below his remarks)
>
> > There are neither theoretical nor observational reasons to be
> > concerned about AGEs in the diet. Most especially since they
> > frequently are seen in food that is not healthy for other reasons, and
> > is usually avoided by the prudent dieter.
> > Thomas
>
> François Rose- Hide quoted text -
>
> - Show quoted text -
François Rose
jc101
> this practice relates more Vlassara to a huckster than to a scientist
> and I will, in the future, look very carefully (and more than I did)
> when I read an article written by Vlassara.
>
> So I confirm what I said earlier:
>
>
>
> > So what she would have to do (and what she refuses to do or maybe
> > refuses to publish) is the lifespan comparison between the group with
> > low AGE and CR group. And if there would be something interesting
> > there, she would have to add another group (CR with low AGE).
>
> > So I follow Carter's opinion about this study here which is an
> > attempt for Helen Vlassara to link AGE issues with the CR life
> > extension effects because it is very easy to shorten lifespan (what
> > did Vlassara in this study) and the tough part is the contrary (where
> > she did nothing).
>
> > So the life extending effect of a low
>
>
> read more »- Hide quoted text -
>
> - Show quoted text -- Hide quoted text -
>
> - Show quoted text -
OK, found the data. The survival data on Low vs Reg is shown in her
previous work in Am J Pathology last year.17525257 Full text link :
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17525257
Table 3 shows the lifespan percentiles in this earlier study of Low
AGE vs Reg AGE. The lifespan percentiles are almost identical to the
CR vs Reg results in the newer article shown in Table 4 except that
the maximum lifespan was an extra 6 days (5%) on Low compared to CR.
So that is why Fig 10 shows that CR and Low had the same p value
compared to Reg. The Low data was published in this earlier work, so
it was not repeated in the newest article.
But, although now we know that just less cooking will do just as well
as calorie restriction and even gave longer maximum lifespan (per this
study), one does not receive the gherelin buzz and all the
psychological benefits of starvation, so dysorexics should ignore all
this Vlassara data and continue obsessing on skin folds and BMI.
JLC
jc101
>
> Table 3 shows the lifespan percentiles in this earlier study of Low
> AGE vs Reg AGE. The lifespan percentiles are almost identical to the
> CR vs Reg results in the newer article shown in Table 4 except that
> the maximum lifespan was an extra 6 days (5%) on Low compared to CR.
> So that is why Fig 10 shows that CR and Low had the same p value
> compared to Reg. The Low data was published in this earlier work, so
> it was not repeated in the newest article.
>
> But, although now we know that just less cooking will do just as well
> as calorie restriction and even gave longer maximum lifespan (per this
> study), one does not receive the gherelin buzz and all the
> psychological benefits of starvation, so dysorexics should ignore all
> this Vlassara data and continue obsessing on skin folds and BMI.
> JLC
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17525257
François Rose
I was also following this track because Vlassara states in one of her
paper that low AGE extend lifespan
Of course, one can't bring together the results of the two studies
and acts as if they were one unique study; one can't say that the
lifespan from this study is higher than the lifespan of that study in
order to infer that this regimen is better. If one want to do that, he/
she would have to do another lifespan study in order to test his/her
new hypothesis.
So my first comment is this:
Vlassara has done two separate lifespan studies:
one, that I commented above, that shows that a high AGE content
cancels the life extending effect of CR (that is, IMO, a non useful
study regarding life extension)
Vlassara repeats elsewhere that low AGE extend lifespan
but AFAIK, her claims is only based on only one of her paper (I'd be
glad to be contradicted on that point)
http://tinyurl.com/4o5yew pmid 17525257
>From the full text:
"The body weight did not differ between the groups, until ~96 weeks of
age, when a modest decline in total weight was noted in LowAGE mice (P
< 0.01), despite identical food consumption (Figure 1)."
Thus the body weight differs significantly from the 96 weeks of age.
see http://tinyurl.com/6dnrdw
So in my opinion, it is merely a crypto CR effect (at least for the
significative part since the weight difference is significative)
>From the full text:
"Thus, compared with RegAGE, which is first steam-conditioned and
pelleted at 70 to 75°C, for 1 to 2 minutes, and then dried at 55°C for
30 minutes, LowAGE was only exposed to 80°C for 1 minute, during
pelleting."
So maybe I'm wrong but could I infer that the dried food of the RegAge
group has a higher caloric content per kg than the one of the LowAge
which is not dried (since water could have been evaporated)? (The
Food/
day/mouse is identical in both groups: 5 g)
That would explain the crypto CR effect.
So once again, I'm not convinced by this paper from Vlassara and I'm
actually thinking that Thomas Carter's position is more consistent
with reality: see again his post http://tinyurl.com/5k7549
If anyone has a comment about that (especially a different well-backup
point of view), I'd be interested.
(I've just become a bit suspicious and less enthusiastic about
Vlassara's papers)
(I say it again, I read Vlassara's theories about a year ago here:
http://tinyurl.com/5myyrq
(this link is probably locked) and following that, I've,as often as
possible, cooked at low temperatures and/or eaten raw food)
François Rose
Olafur Pall Olafsson
François Rose wrote:
> On Jul 17, 8:16�pm, jc101 <uniqueprodu...@comcast.net> wrote:
[snip]
> Vlassara repeats elsewhere that low AGE extend lifespan
> but AFAIK, her claims is only based on only one of her paper (I'd be
> glad to be contradicted on that point)
> http://tinyurl.com/4o5yew pmid 17525257
That is the only paper of which I am aware in which a low AGE diet was
reported to increase lifespan.
> >From the full text:
> "The body weight did not differ between the groups, until ~96 weeks of
> age, when a modest decline in total weight was noted in LowAGE mice (P
> < 0.01), despite identical food consumption (Figure 1)."
> Thus the body weight differs significantly from the 96 weeks of age.
> see http://tinyurl.com/6dnrdw
>
> So in my opinion, it is merely a crypto CR effect (at least for the
> significative part since the weight difference is significative)
>
> >From the full text:
> "Thus, compared with RegAGE, which is first steam-conditioned and
> pelleted at 70 to 75�C, for 1 to 2 minutes, and then dried at 55�C for
> 30 minutes, LowAGE was only exposed to 80�C for 1 minute, during
> pelleting."
>
> So maybe I'm wrong but could I infer that the dried food of the RegAge
> group has a higher caloric content per kg than the one of the LowAge
> which is not dried (since water could have been evaporated)? (The
> Food/
> day/mouse is identical in both groups: 5 g)
> That would explain the crypto CR effect.
That is an interesting hypothesis that had not occurred to me. I do
not think it is likely that the LowAGE diet had higher water content
though since any good scientist would've made sure the caloric density
of the diets was the same, not doing so would've been very stupid or
fraudulent. But I am not sure, the text doesn't make this clear. What
I am wondering is, what exactly did they mean by "LowAGE was only
exposed to 80�C for 1 minute"? Do they mean the LowAGE was not steam-
conditioned first like the RegAGE food or do they mean that, after
being steam-conditioned like the RegAGE food the LowAGE food was only
exposed to 80°C for 1 minute. In the latter case the "only" would
refer to the much shorter time of exposure to heat compared to the
RegAGE food. I don't think this can be solved without contacting the
author.
BTW regarding the possibility of a crypto CR effect. I noticed looking
at figure 1 in the full text article that although there wasn't a
significant difference in food intake between the groups at any time
point, at *all time points* the food intake was non-significantly
higher in the LowAGE group. The chances of that being a coincidence
are not very high and this I think reduces the chances that the
difference in body weights between the groups was caused by a crypto
CR effect.
> So once again, I'm not convinced by this paper from Vlassara and I'm
> actually thinking that Thomas Carter's position is more consistent
> with reality: see again his post http://tinyurl.com/5k7549
Regarding Thomas Carter's comments. I can see that Vlassara looks a
little suspicious given her long history of publishing studies that
show AGEs as negative. I know I myself will be more vary of anything
she has published for now on. But I think he has gone too far in his
statements about her. He is stating that he knows her and that she
"has been for decades dreaming up experiments that are designed to
prove her point". Where is the evidence for that? Yes I realize she
has published lots of studies showing AGEs in a negative light, but
assuming he has never met her in person or conversed with her in any
way I don't think he is in any position to make such statements about
her based merely on the studies she has published. If she were
publishing a lot of studies on some drug she might have vested
interest in (perhaps being sponsored by a drug company) I would be
more suspicious but I can't see what motivation she would have for
trying to prove that AGEs are negative as Thomas appears to think.
François Rose
wrote:
> François Rose wrote:
> > On Jul 17, 8:16�pm, jc101 <uniqueprodu...@comcast.net> wrote:
>
> [snip]
>
> > Vlassara repeats elsewhere that low AGE extend lifespan
> > but AFAIK, her claims is only based on only one of her paper (I'd be
> > glad to be contradicted on that point)
> >http://tinyurl.com/4o5yew pmid 17525257
>
> That is the only paper of which I am aware in which a low AGE diet was
> reported to increase lifespan.
>
>
>
>
>
> > >From the full text:
> > "The body weight did not differ between the groups, until ~96 weeks of
> > age, when a modest decline in total weight was noted in LowAGE mice (P
> > < 0.01), despite identical food consumption (Figure 1)."
> > Thus the body weight differs significantly from the 96 weeks of age.
>
> Regarding Thomas Carter's comments. I can see that Vlassara looks a
> little suspicious given her long history of publishing studies that
> show AGEs as negative. I know I myself will be more vary of anything
> she has published for now on. But I think he has gone too far in his
> statements about her. He is stating that he knows her and that she
> "has been for decades dreaming up experiments that are designed to
> prove her point". Where is the evidence for that? Yes I realize she
> has published lots of studies showing AGEs in a negative light, but
> assuming he has never met her in person or conversed with her in any
> way I don't think he is in any position to make such statements about
> her based merely on the studies she has published. If she were
> publishing a lot of studies on some drug she might have vested
> interest in (perhaps being sponsored by a drug company) I would be
> more suspicious but I can't see what motivation she would have for
>
> - Show quoted text -
I'm still trying to understand the lifespan results of this study by
Vlassara:
http://tinyurl.com/4o5yew pmid 17525257
(which is, AFAIK, the only study that shows a longer lifespan with a
Low AGE diet versus controls)
My first idea that LowAGE diet had higher water content seems wrong
since, from the full text:
"Mice were assigned to two dietary groups (Table 1): a regular NIH-31
open formula (Harlan Teklad, Madison, WI) ad lib (RegAGE), and a
rodent chow diet (LabDiet 5053; LabDiet, Purina Mills, Richmond, IN),
equal in calories, nutrient, and micronutrient content to RegAGE, but,
by limiting exposure to the standard temperature during manufacture,
contained less measurable CML-like AGEs"
So the diets were already treated when they were purchased and they
were "equal in calories, nutrient, and micronutrient content "
Anyway, the crypto CR effect is still there:
there is a significant weight difference between Low AGE and High AGE;
so this significant weight difference consequences a lifespan increase
(because of the well established life extending CR effect).
Another idea to explain this: from 6293296
"Effect of processing on digestibility and the blood glucose response:
a study of lentils"
"However the blood glucose response was significantly enhanced by
drying the boiled blended lentils for 12 h at 250 degrees F. In vitro
digestion with human saliva showed the rate of sugars released from
the food related positively to the blood glucose rise. Breath hydrogen
studies indicated that carbohydrate malabsorption was too small to
account for differences in the blood glucose response. These results
emphasize the importance of processing in determining digestibility
and hence the glycemic response to a food."
Drying lentils increases their glycemic index
From Vlassara's study: "compared with RegAGE, which is first steam-
conditioned and pelleted at 70 to 75°C, for 1 to 2 minutes, and then
dried at 55°C for 30 minutes, LowAGE was only exposed to 80°C for 1
minute, during pelleting. "
So : the food processing was different so the glycemic index in the
LowAGE group was lower and consequences a lower weight (I haven't
backup that a lower Glycemic Index consequences a lower weight intake
because I assume it is well known )
Any idea about that?
(Thanks to Olafur to discuss without mocking about my first hypothesis
(water content))
François Rose
Olafur Pall Olafsson
> On Jul 18, 10:43 am, Olafur Pall Olafsson <olafurp...@yahoo.com>
> wrote:
>
>
>
> > François Rose wrote:
>
> > [snip]
>
> > > Vlassara repeats elsewhere that low AGE extend lifespan
> > > but AFAIK, her claims is only based on only one of her paper (I'd be
> > > glad to be contradicted on that point)
> > >http://tinyurl.com/4o5yew pmid 17525257
>
> > That is the only paper of which I am aware in which a low AGE diet was
> > reported to increase lifespan.
>
> > > >From the full text:
> > > "The body weight did not differ between the groups, until ~96 weeks of
> > > age, when a modest decline in total weight was noted in LowAGE mice (P
> > > < 0.01), despite identical food consumption (Figure 1)."
> > > Thus the body weight differs significantly from the 96 weeks of age.
> > > seehttp://tinyurl.com/6dnrdw
>
> > > So in my opinion, it is merely a crypto CR effect (at least for the
> > > significative part since the weight difference is significative)
>
> > > >From the full text:
> > > "Thus, compared with RegAGE, which is first steam-conditioned and
> > > 30 minutes, LowAGE was only exposed to 80?C for 1 minute, during
> > > pelleting."
>
> > > So maybe I'm wrong but could I infer that the dried food of the RegAge
> > > group has a higher caloric content per kg than the one of the LowAge
> > > which is not dried (since water could have been evaporated)? (The
> > > Food/
> > > day/mouse is identical in both groups: 5 g)
> > > That would explain the crypto CR effect.
>
> > That is an interesting hypothesis that had not occurred to me. I do
> > not think it is likely that the LowAGE diet had higher water content
> > though since any good scientist would've made sure the caloric density
> > of the diets was the same, not doing so would've been very stupid or
> > fraudulent. But I am not sure, the text doesn't make this clear. What
> > I am wondering is, what exactly did they mean by "LowAGE was only
> (which is, AFAIK, the only study that shows a longer lifespan with a
> Low AGE diet versus controls)
>
> My first idea that LowAGE diet had higher water content seems wrong
> since, from the full text:
> "Mice were assigned to two dietary groups (Table 1): a regular NIH-31
> open formula (Harlan Teklad, Madison, WI) ad lib (RegAGE), and a
> rodent chow diet (LabDiet 5053; LabDiet, Purina Mills, Richmond, IN),
> equal in calories, nutrient, and micronutrient content to RegAGE, but,
> by limiting exposure to the standard temperature during manufacture,
> contained less measurable CML-like AGEs"
> So the diets were already treated when they were purchased and they
> were "equal in calories, nutrient, and micronutrient content "
I agree the idea that the LowAGE diet had higher water content was not
correct given this information.
> Anyway, the crypto CR effect is still there:
> there is a significant weight difference between Low AGE and High AGE;
> so this significant weight difference consequences a lifespan increase
> (because of the well established life extending CR effect).
I think this is a wrong conclusion. I do not think this can be
correctly termed crypto CR. As table 1 in the full text reports the
total calories consumed per day in the regular group was 20,0 while in
the lowAGE group they were 20,1 which is even higher than in the
regular group. From this information one cannot conclude that the
lowAGE group was restricting their calories compared to the highAGE
group. This suggests that the difference in body weights between the
groups was not caused by difference in their calorie intake. Therefore
any difference in their weight must have been caused by differences in
their metabolic rates, IOW the mice in the lowAGE group must have had
a higher metabolic rate than those in the regAGE group. Based on this
I think the lowAGE group had lower amounts of body fat and more muscle
mass since muscle tissue burns considerably more calories than fat
tissue. Unfortunately this cannot be confirmed since the body
composition of the mice was not measured.
> Another idea to explain this: from 6293296
> "Effect of processing on digestibility and the blood glucose response:
> a study of lentils"
> "However the blood glucose response was significantly enhanced by
> drying the boiled blended lentils for 12 h at 250 degrees F. In vitro
> digestion with human saliva showed the rate of sugars released from
> the food related positively to the blood glucose rise. Breath hydrogen
> studies indicated that carbohydrate malabsorption was too small to
> account for differences in the blood glucose response. These results
> emphasize the importance of processing in determining digestibility
> and hence the glycemic response to a food."
> Drying lentils increases their glycemic index
While it is possible that the heating might have increased the
glycemic index of the rat chow I do not think such a conclusion can be
made from this study. Rat chow is not made of lentils, and lentils
contain antinutrients that may reduce the digestion rate and
absorption of carbohydrates. While these are generally heat stable
they might have been destroyed by the heating, possibly causing the
difference seen in that study.
> From Vlassara's study: "compared with RegAGE, which is first steam-
> conditioned and pelleted at 70 to 75°C, for 1 to 2 minutes, and then
> dried at 55°C for 30 minutes, LowAGE was only exposed to 80°C for 1
> minute, during pelleting. "
> So : the food processing was different so the glycemic index in the
> LowAGE group was lower and consequences a lower weight (I haven't
> backup that a lower Glycemic Index consequences a lower weight intake
> because I assume it is well known )
> Any idea about that?
As I explained above I don't think you can conclude from this that the
GI in the lowAGE group was any higher than that of the regAGE groups.
And while it is probably well known, at least among health conscious
people, that a low GI diet helps people lose weight I think the reason
for that is mostly because in general low GI foods have more fiber and
keep the blood sugar more stable. This results in increased satiety
and may decrease hunger pangs from quick drops in blood glucose, thus
the end results is that people tend to eat less on a low GI diet. But
I don't think it is true that a low GI diet has any advantage compared
to a high GI diet with respect to weight loss if the calorie content
is constant like it was in this study. If there is any difference then
it is probably not significant. As always in the end it is the calorie
intake that is the most important aspect when it comes to weight loss.
It is clear from the fact that the lowAGE group did not eat fewer
calories than the regAGE group that the lowAGE group must have burned
more calories than the regAGE group. What caused this difference I am
not sure. I think the AGEs in the diet must have had some indirect
effects that resulted in slight differences in their activity or
muscle to fat ratio that over time became significant enough to cause
the difference in weight. Higher activity as well as a higher muscle
to fat ratio both lead to increased calorie expenditure. There are
many things that might cause this but I can't think of any single
major effect of AGE consumption that would cause this. An example of a
hypothesis that comes to my mind is that the AGEs in the diet caused
inflammation resulting in higher levels of the inflammatory cytokine
IL-6 in the regAGE group. High levels of IL-6 in the brain cause
chronic fatique so the increase in IL-6 could've reduced the physical
activity of the rats in the regAGE group leading to lower calorie
expenditure and higher weight gain. This is just an example of a
hypothesis that might partly explain the difference. I really don't
know what caused the difference in weight.
> (Thanks to Olafur to discuss without mocking about my first hypothesis
> (water content))
I don't see any point in mocking anyone that is making an honest
effort to contribute to this group and is here to learn. Mocking is
usually something insecure individuals do in an attempt to belittle
someone and in doing so to feel better about themselves. I don't do
such things. And there is nothing to be ashamed of for making a
hypothesis that doesn't turn out to be true. If anything that
hypothesis shows that you are making good use of your imagination.
jc101
> > > > been for decades dreaming up experiments that are designed to
> > > > prove her point."
> > > > She takes three groups: a control group, a CR group and a CR group
> > > > with a higher load of dietary AGE and she proves that this last group
> > > > has a lower lifespan than the control group.
>
> > > > Strangly, she had done tests with five groups (control, CR, CR with
> > > > high AGE diet, low AGE diet, low AGE diet + a specific AGE )
> > > > and life comparison only with three groups
>
> > > > So what she would have to do (and what she refuses to do or maybe
> > > > refuses to publish) is the lifespan comparison between the group with
> > > > low AGE and CR group. And if there would be something interesting
> > > > there, she would have to add another group (CR with low AGE).
>
> > > > So I follow Carter's opinion about this study here which is an
> > > > extension effects because it is very easy to shorten lifespan (what
> > > > she did nothing).
>
> > > > So the life extending effect of a low AGE diet has yet to be proved
> > > > and Thomas 's remarks about the unnecessity of changing diet seems
> > > > reasonable to me actually. (I've pasted below his remarks)
>
> > > > > There are neither theoretical nor observational reasons to be
> > > > > concerned about AGEs in the diet. Most especially since they
> > > > > frequently are seen in food that is not healthy for other reasons, and
> > > > > is usually avoided by the prudent dieter.
> > > > > Thomas
>
> > > > François Rose- Hide quoted text -
>
> > > > - Show quoted text -
>
> > can't
> > prove) since the very authors
> > tell that there is no lifespan study for the low group (what I regret
> > since this lack takes off all value to this study))
>
> > effects of a CR diet may be
> > partly related to reduced oxidant intake, a principal determinant of
> > oxidant status in aging mice, rather than decreased energy intake. "
> > The only thing she has proved is : "the beneficial effects of a CR
> > diet can be reduced and even cancelled by adding a high AGE dietary
> > load".
> > The only thing she has achieved is reducing the beneficial effects of
> > CR diet. What 's the point? What she has to do is to extend life span.
>
> > I consider as an intellectual dishonesty to mix up lab tests between
> > 5
> > groups and lifespan between 3 out of these 5 groups in order to infer
> > lifespan conclusions about the 5 groups; this is why I think that
> > Thomas
> > Carter could be right in his posthttp://tinyurl.com/5k7549andthat
> > and I will, in the future, look very carefully (and more than I did)
> > when I read an article written byVlassara.
>
> > So I confirm what I said earlier:
>
> > > So what she would have to do (and what she refuses to do or maybe
> > > refuses to publish) is the lifespan comparison between the group with
> > > low AGE and CR group. And if there would be something interesting
> > > there, she would have to add another group (CR with low AGE).
>
> > > So I follow Carter's opinion about this study here which is an
> > > extension effects because it is very easy to shorten lifespan (what
> > > she did nothing).
>
> > > So the life extending effect of a low
>
> > ...
>
> > read more »- Hide quoted text -
>
> > - Show quoted text -- Hide quoted text -
>
> > - Show quoted text -
>
> OK, found the data. The survival data on Low vs Reg is shown in her
>
> Table 3 shows the lifespan percentiles in this earlier study of Low
> AGE vs Reg AGE. The lifespan percentiles are almost identical to the
> CR vs Reg results in the newer article shown in Table 4 except that
> the maximum lifespan was an extra 6 days (5%) on Low compared to CR.
> So that is why Fig 10 shows that CR and Low had the same p value
> compared to Reg. The Low data was published in this earlier work, so
> it was not repeated in the newest article.
>
> But, although now we know that just less cooking will do just as well
> as calorie restriction and even gave longer maximum lifespan (per this
> study), one does not receive the gherelin buzz and all the
> psychological benefits of starvation, so dysorexics should ignore all
> JLC
Dr. Striker, one of the authors of the two papers in Am. J. of
Pathology, responded to my email and confirmed that these were
concurrent studies with results published in two separate papers.
These two articles begin a new era in life extension, ending the
mantra of calorie restriction, since it has been demonstrated that 1)
any benefits of CR on lifespan have to do with lowered AGE
consumption, not lowered calories and 2) More cooking that creates
high levels of AGEs defeats CR effects. Anyone serious about life
extension will forget about CR and move to the best and healthiest BMI
of 22-25 and just spend their devotion in lowering AGE consumption and
internal production.
Devotees of CRON will continue for the neuroendocrinological 'ghrelin
buzz' which is the dopaminergic and opiate system activation caused by
partial starvation. This can be addictive, just as alcohol and drugs
and gambling are for susceptible individuals in unsatisfying life
circumstances.
JLC