48 replies to this topic

[mikeinnaples]

Michael gave a link to the article when he started this thread.

Basically, the resveratrol-fed mice developed cancer and died without an extension of maximal life-span, unlike CR where the mice did not get cancer and lived longer.

Yup I read that, several times. I still don't see where it flunks real world v. cancer. To be honest, I could say that any well known drug fails to achieve its desired effect if the dosage is too small to trigger the mechanisms that exhibit the end effect. I can also make a post stating: "Water flunks against real world dehydration." because test subjects (humans) were only taking .5ml a day while being subjected to summer heat conditions. The studies showing that Resveratrol 'passes' vs. real world cancer ave used drastically higher doses. I really fail to see why pinning a militant counterpoint is more important than some of the other discussions we have had here especially with the misleading subject title.

[kismet]

You are wrong: the res treated mice died w/o maximum life extension? Hell, no!
"Our study design involved the use of a long-lived F1 hybrid mouse strain, and sacrificing mice at 30-months of age, therefore we were unable to evaluate effects of resveratrol on average or maximum lifespan. "
Thus it will take more than that to fully debunk resveratrol (or show its efficacy for that matter).

Michael is right, he does take some supplements which are proven, but taking not well researched supps when practising CR (CR on the contrary is well researched) could negate all the CR benefits...

[edward]

snip...
Michael is right, he does take some supplements which are proven, but taking not well researched supps when practising CR (CR on the contrary is well researched) could negate all the CR benefits...

Perhaps more accurately, could over enhance CRs effects yielding negative results...

[VictorBjoerk]

Apparently Michael consumes resveratrol through natural sources (pinot noir) which however only contains very little of the substance.

Hasn't there been any major studies on fat humans being administered with resveratrol when being fed ad lib? Does anyone have access to any of these studies,and what are the conclusions,?

[inawe]

Michael Rae practices CR,a nd has been, well, some say hostile, to any supplemental intervention to try and mimic its effects. He is also very intelligent and makes some good points. I learned from his post that unlike CR resveratrol does not modulate IGF-1

The IGF-1 stuff was in the Weindruch paper.
Years ago Guarente, Sinclair and others found that CR extended life in several organisms by causing overexpression of SIRT1. The CR
enthusiasts seemed to be happy with this explanation. No complains were heard from them.
But the CR enthusiasts do react when the possibility of having a CR mimetic is brought up.
The new paper by Weindruch et al. changes things quite a bit. No SIRT1 overexpression was seen in CR mice. So the headline for a thread like this could as well have been:

CR Flunks the SIRT1 Test. How Do We Explain Now Any Possible CR Benefit?

[mikeinnaples]

The new paper by Weindruch et al. changes things quite a bit. No SIRT1 overexpression was seen in CR mice. So the headline for a thread like this could as well have been:
CR Flunks the SIRT1 Test. How Do We Explain Now Any Possible CR Benefit?

Agreed.

[maxwatt]

Michael Rae practices CR,a nd has been, well, some say hostile, to any supplemental intervention to try and mimic its effects. He is also very intelligent and makes some good points. I learned from his post that unlike CR resveratrol does not modulate IGF-1

The IGF-1 stuff was in the Weindruch paper.
Years ago Guarente, Sinclair and others found that CR extended life in several organisms by causing overexpression of SIRT1. The CR
enthusiasts seemed to be happy with this explanation. No complains were heard from them.
But the CR enthusiasts do react when the possibility of having a CR mimetic is brought up.
The new paper by Weindruch et al. changes things quite a bit. No SIRT1 overexpression was seen in CR mice. So the headline for a thread like this could as well have been:

CR Flunks the SIRT1 Test. How Do We Explain Now Any Possible CR Benefit?

CR upregulates some of the same things Sort1 upregulates, without overexpression of Sirt1?

[krillin]

CR Flunks the SIRT1 Test. How Do We Explain Now Any Possible CR Benefit?

Let's be careful to remember the distinction between expression and activation. SIRT1 expression wasn't induced by anything in this study, but SIRT1 was definitely activated by CR. It wasn't activated by resveratrol because the dose was too low.

Feeding high levels of resveratrol to mice has been shown to be associated with increased SIRT1 activity as measured by PGC-1α acetylation and induction of its transcriptional targets [8], [9]. Because sirtuin overexpression increases longevity in some organisms and may mediate some of the effects of CR [3], [4], the induction of SIRT1 activity has been postulated to mediate the health benefits of resveratrol [8], [9]. We investigated if alterations in the levels of SIRT1 or induction of PGC-1α transcriptional activity can explain the observation that a low dose of resveratrol mimics CR. In contrast to previous finding in rats [23] and humans [24], neither CR nor resveratrol feeding significantly altered the levels of SIRT1 protein in brain or liver of mice, and SIRT1 abundance was actually significantly decreased in both heart and muscle of CR mice (Figure 3A). However, CR clearly increased the mRNA levels of Pgc-1α in skeletal muscle. CR also stimulated an increase in Pgc-1α transcriptional targets Pdk4 and Ucp3 in heart and skeletal muscle. In contrast, resveratrol did not significantly increase the levels of Pgc-1α expression or any of its transcriptional targets, with the exception of a small effect on the expression of Pdk4 in skeletal muscle (Figure 3B). Thus, our microarray results suggest that a low dose of dietary resveratrol induces a transcriptional program similar to CR in multiple tissues and retards aging parameters, but these effects may be largely independent of the increase in SIRT1 activity and activation of Pgc-1α transcriptional targets reported previously for mice in a high fat diet fed high levels of resveratrol [8], [9].

[inawe]

CR Flunks the SIRT1 Test. How Do We Explain Now Any Possible CR Benefit?

Let's be careful to remember the distinction between expression and activation. SIRT1 expression wasn't induced by anything in this study, but SIRT1 was definitely activated by CR. It wasn't activated by resveratrol because the dose was too low.

Feeding high levels of resveratrol to mice has been shown to be associated with increased SIRT1 activity as measured by PGC-1α acetylation and induction of its transcriptional targets [8], [9]. Because sirtuin overexpression increases longevity in some organisms and may mediate some of the effects of CR [3], [4], the induction of SIRT1 activity has been postulated to mediate the health benefits of resveratrol [8], [9]. We investigated if alterations in the levels of SIRT1 or induction of PGC-1α transcriptional activity can explain the observation that a low dose of resveratrol mimics CR. In contrast to previous finding in rats [23] and humans [24], neither CR nor resveratrol feeding significantly altered the levels of SIRT1 protein in brain or liver of mice, and SIRT1 abundance was actually significantly decreased in both heart and muscle of CR mice (Figure 3A). However, CR clearly increased the mRNA levels of Pgc-1α in skeletal muscle. CR also stimulated an increase in Pgc-1α transcriptional targets Pdk4 and Ucp3 in heart and skeletal muscle. In contrast, resveratrol did not significantly increase the levels of Pgc-1α expression or any of its transcriptional targets, with the exception of a small effect on the expression of Pdk4 in skeletal muscle (Figure 3B). Thus, our microarray results suggest that a low dose of dietary resveratrol induces a transcriptional program similar to CR in multiple tissues and retards aging parameters, but these effects may be largely independent of the increase in SIRT1 activity and activation of Pgc-1α transcriptional targets reported previously for mice in a high fat diet fed high levels of resveratrol [8], [9].

Why don't you reread carefully what you just quoted from Weindruch's paper. Once more with gusto:
"resveratrol induces a transcriptional program similar to CR in multiple tissues and retards aging parameters, but these effects may be largely independent of the increase in SIRT1 activity".
independent of the increase in SIRT1 activity
independent of the increase in SIRT1 activity
......

[krillin]

Why don't you reread carefully what you just quoted from Weindruch's paper. Once more with gusto:
"resveratrol induces a transcriptional program similar to CR in multiple tissues and retards aging parameters, but these effects may be largely independent of the increase in SIRT1 activity".
independent of the increase in SIRT1 activity
independent of the increase in SIRT1 activity
......

That is not in conflict with what I wrote. Low dose resveratrol does some of what CR does, with a notable exception of SIRT1 activation. High dose resveratrol also activates SIRT1, just like CR does.

Do you retract your claim that "CR Flunks the SIRT1 Test"?

[inawe]

Why don't you reread carefully what you just quoted from Weindruch's paper. Once more with gusto:
"resveratrol induces a transcriptional program similar to CR in multiple tissues and retards aging parameters, but these effects may be largely independent of the increase in SIRT1 activity".
independent of the increase in SIRT1 activity
independent of the increase in SIRT1 activity
......

That is not in conflict with what I wrote. Low dose resveratrol does some of what CR does, with a notable exception of SIRT1 activation. High dose resveratrol also activates SIRT1, just like CR does.

Do you retract your claim that "CR Flunks the SIRT1 Test"?

Absolutely, I retract you.

[TianZi]

Any person who undertakes a severe CR diet to extend their lifespan is likely to have a zealous belief that the diet will produce effects that currently cannot be replicated in any other way. As such persons must make a substantial sacrifice in order to pursue this goal through CR, they will probably tend to be more skeptical than the average person about alternatives that may have the same or similar health benefits. If you suffer to achieve an end, you may be less likely to accept the same end could be achieved sans suffering.

As I believe Michael himself has said, a person's natural tendency is to embrace ideas and conclusions that reinforce his own prexisting beliefs, while rejecting those which don't.

If this thread is to remain pinned, the title really needs to be changed. Otherwise, the Immortality Institute itself seems to be advocating Michael's completely unproven assertion (per the thread title) that resveratrol at ANY dosage does not have cancer protective effects. The authors of the U. of Wis. study made no such broad claims based on the results of their study, but instead carefully limited their conclusions by acknowledging that the effects of resveratrol given at higher doses may have different effects, including inducing SIRT1 activation and perhaps cancer preventive effects.

Since Michael has primarily supported his assertion that resveratrol does not have cancer protective effects by selectively quoting from said U. of Wis. study authored by Weindruch, the following quote from said study by Weindruch needs to be included to understand Weindruch's conclusions in the proper context:

"It is likely that the effects of resveratrol feeding at lower doses reported here are distinct than [sic] those observed with higher doses, with particular relevance to the induction of SIRT1 activity."

Edited by TianZi, 19 June 2008 - 08:29 AM.

[zawy]

Any person who undertakes a severe CR diet to extend their lifespan is likely to have a zealous belief that the diet will produce effects that currently cannot be replicated in any other way. As such persons must make a substantial sacrifice in order to pursue this goal through CR,

I don't view CR to be any more of a sacrifice than exercise or studying to increase knowledge. I dread going out to eat not because it will break my CR routine, but because of the pain in my stomach and mood after over-eating, and the knowledge that it increases abdominal fat. The biggest sacrifice is from not giving in to the social pressure of eating as much as others. Partaking of a meal together is an important social event and refusing to do so in its fullness is viewed as refusing to be a part of the group, be it family, friends, or co-workers. They also get angry at you for not wanting to be as fat and for having more discipline because it REMINDS them everytime you sit down in front of them that they are lazy and fat.

Edited by zawy, 23 June 2008 - 01:27 PM.

[tintinet]

Any person who undertakes a severe CR diet to extend their lifespan is likely to have a zealous belief that the diet will produce effects that currently cannot be replicated in any other way. As such persons must make a substantial sacrifice in order to pursue this goal through CR,

I don't view CR to be any more of a sacrifice than exercise or studying to increase knowledge. I dread going out to eat not because it will break my CR routine, but because of the pain in my stomach and mood after over-eating, and the knowledge that it increases abdominal fat. The biggest sacrifice is from not giving in to the social pressure of eating as much as others. Partaking of a meal together is an important social event and refusing to do so in its fullness is viewed as refusing to be a part of the group, be it family, friends, or co-workers. They also get angry at you for not wanting to be as fat and for having more discipline because it REMINDS them everytime you sit down in front of them that they are lazy and fat.

I usually eat as much or more (in terms of volume) than non-CR folk I'm with. I just eat mostly salads and vegetables...

[inawe]

I came to the forum and was shocked to see that this thread was unpinned. Does it mean that the subject became less important?
The paper that inspired the topic compared the effects of Calorie Restriction (CR) and resveratrol. Contrary to what some previous researchers told us, it's becoming obvious that CR is not a good mimetic of RSV. So my advice would be: Don't starve yourself. Go for the real thing. After all RSV is not that expensive.

[kismet]

... Contrary to what some previous researchers told us, it's becoming obvious that CR is not a good mimetic of RSV. So my advice would be: Don't starve yourself. Go for the real thing. After all RSV is not that expensive.

Yes, that's one interpretation. Though, most would see it the other way round, RSV is not a good CR mimetic... and describing RSV as the "real thing" in comparison to CR is a joke, I guess? (even on the RSV subforums people should know that CR seems superior from our current understanding.)

[Shepard]

I came to the forum and was shocked to see that this thread was unpinned. Does it mean that the subject became less important?

Depending on the quality of the discussion that occurs will determine whether or not it stays pinned.

[sUper GeNius]

I came to the forum and was shocked to see that this thread was unpinned. Does it mean that the subject became less important?
The paper that inspired the topic compared the effects of Calorie Restriction (CR) and resveratrol. Contrary to what some previous researchers told us, it's becoming obvious that CR is not a good mimetic of RSV. So my advice would be: Don't starve yourself. Go for the real thing. After all RSV is not that expensive.

That's funny. I believe the word the researcher used in describing the similarity in gene expression was "remarkable."

[inawe]

I came to the forum and was shocked to see that this thread was unpinned. Does it mean that the subject became less important?

Depending on the quality of the discussion that occurs will determine whether or not it stays pinned.

OK. I'll take some of the credit for lowering the "quality of the discussion". Some of the credit but not all, I'm not that selfish.