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Resveratrol extends lifespan in mice by 30%


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#1 maxwatt

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Posted 13 November 2007 - 04:36 AM


I apologize for ntroducing yet another resveratrol thread, but this may be important to some here. Sinclair has not yet published the last part of his mouse study that started the furor: the one last October that showed mice fed a high fat diet were in bettter health if fed resveratrol. He also mentioned he was compaing mice on a normal diet. Though I don't know of a presentation, the Sirtris presentation at JP Morgans Mid Cap Boston Conference made the claim that mouse lifespan was increased by 30% with resveratrol. If anyone can find the paper, let us know.

Sirtris claim in this presentation that resveratrol extends mouse life span by 30%: Sirtris Pharmaceuticals at JPMorgan SMid Cap Boston Conference

Look for Slide 7. The slide is ambiguous, in that it could refer to calorie restriction, but the audio appeared to imply that resveratrol had this effect.

#2 billypc99

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Posted 13 November 2007 - 06:02 PM

maxwatt,

I believe this part of the presentation was intentionally ambiguous to help lead the horse to water. In slide 7, the ambiguous phrase "healthy lifespan" is used when referring to the 30% extension of lifespan in mice. Most would take away that this means the normal mice. However, it is actually referring to the mice on a high fat diet with resveratrol vs. those on a high fat diet without resveratrol. This was carefully qualified in slide 5 when explaining the survival curves of the HF groups in which the term "healthy lifespan" was used to describe the 30% increase in survival. Very sneaky.

Sinclair has not yet published the data from the normal mice, which has raised curiosity and suspicion in the scientific community. The consensus is that resveratrol likely had little or no effect on lifespan in the normal group. If this is true and the findings are published, then this could have a negative financial impact, especially at this stage in the game (pre/immediately post IPO and key investments). Therefore, one in this situation may want to delay the publication. In mice/rats, showing lifespan extension and/or an amelioration of the pathologies with a harmful diet has and can been demonstrated with a variety of nutrients (leucine, probiotics,etc). However, demonstrating lifespan extension with a normal diet has not been shown.

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#3 inawe

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Posted 13 November 2007 - 10:29 PM

maxwatt,

I believe this part of the presentation was intentionally ambiguous to help lead the horse to water.  In slide 7, the ambiguous phrase "healthy lifespan" is used when referring to the 30% extension of lifespan in mice.  Most would take away that this means the normal mice.  However, it is actually referring to the mice on a high fat diet with resveratrol vs. those on a high fat diet without resveratrol.  This was carefully qualified in slide 5 when explaining the survival curves of the HF groups in which the term "healthy lifespan" was used to describe the 30% increase in survival.  Very sneaky.   

Sinclair has not yet published the data from the normal mice, which has raised curiosity and suspicion in the scientific community.  The consensus is that resveratrol likely had little or no effect on lifespan in the normal group.  If this is true and the findings are published, then this could have a negative financial impact, especially at this stage in the game (pre/immediately post IPO and key investments).  Therefore, one in this situation may want to delay the publication.  In mice/rats, showing lifespan extension and/or an amelioration of the pathologies with a harmful diet has and can been demonstrated with a variety of nutrients (leucine, probiotics,etc).  However, demonstrating lifespan extension with a normal diet has not been shown.


I'm one of the horses that was lead to RSV. I still have most of 1/2 kilo of 99%+ RSV. I hope it's shown to be a real LE elixir. But I'm a recovering wishful thinker. So when I listen to a Sirtris presentation my reaction is: show me published results (preferable in humans).
Sirtris people are claiming that SRT501 lowers glucose. Just in diabetics? What about in people that have fasting glucose in the 90s (mg/dL)? I never read in this forum that anybody had his/her glucose lowered by taking RSV.
It is also claimed that there are no known side effects. But some people in this forum reported IBS symptoms.
Somebody asked about the other sirtuins. The speaker sort of implied that Sirtris products could also upregulate other sirtuins. And mentioned a work by a Harvard group on the neural effects of SIRT2. Actually, that's a work by Kazantsev's group showing that INHIBITION of SIRT2 can protect against deterioration from Parkinson's disease (PMID: 17588900).

#4 Mind

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Posted 13 November 2007 - 10:40 PM

If they had good data they would be splashing it all over the media...so it is not a good sign that they are being kind-of cagey. Then again, a good scientist will not present until all the data is in and it has been reviewed.

One thing I think we can say with a fair amount of certainty is that there doesn't seem to be any obvious short term toxicity....based on thousands of people mega-dosing RSV and still living.

#5 maxwatt

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Posted 14 November 2007 - 12:11 AM

If they had good data they would be splashing it all over the media...so it is not a good sign that they are being kind-of cagey. Then again, a good scientist will not present until all the data is in and it has been reviewed.

One thing I think we can say with a fair amount of certainty is that there doesn't seem to be any obvious short term toxicity....based on thousands of people mega-dosing RSV and still living.


I believe Sirtris are worried that if resveratrol is shown to be effective in humans, it will destroy their market for their proprietary compounds. When they went public, the investor statement alluded to the risks of marketing SRT-501 as a supplement, for that very reason. even though they could make a good deal of money now by selling SRT501 in health food stores. It is not in their long-term interest to publish good results, much less bad results.

Also in the presentation I cited above, are statements that resveratrol bioavailability in humans is too low to make it practical to administer as a drug. More than two or three capsules a day means "low compliance". I find that their claim SRT501 is four times as potent as resveratrol, and they are doing trials at 5 grams a day, means that to see dramatic effects with non-micronized 99% powder, will require at least 15 grams. Not practical as a commercial product, except for fanatics like some of us.

#6 malbecman

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Posted 14 November 2007 - 07:13 PM

Pretty friendly call-in if you ask me. I've been on ones where the CEO/CFO gets raked over the coals. These analysts seem to be FOS (Friends of Sirtris) and I wouldnt be surprised if their questions werent perhaps a bit staged.
Sirtris is being a good early stage company and keeping their cards pretty close to their chest IMHO......

#7 browser

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Posted 14 November 2007 - 09:18 PM

Pretty friendly call-in if you ask me.  I've been on ones where the CEO/CFO gets raked over the coals.  These analysts seem to be FOS (Friends of Sirtris) and I wouldnt be surprised if their questions werent perhaps a bit staged.
Sirtris is being a good early stage company and keeping their cards pretty close to their chest IMHO......

Perhaps they've learned from pump and dump schemes and the Alteon fiasco.

#8 niner

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Posted 15 November 2007 - 04:19 AM

Also in the presentation I cited above, are statements that resveratrol bioavailability in humans is too low to make it practical to administer as a drug. More than two or three capsules a day means "low compliance". I find that their claim SRT501 is four times as potent as resveratrol, and they are doing trials at 5 grams a day, means that to see dramatic effects with non-micronized 99% powder, will require at least 15 grams. Not practical as a commercial product, except for fanatics like some of us.

Do we have any solid information regarding what exactly is in SRT501 besides resveratrol? I think Tween 80 was mentioned in some presentation, and there was a process using cyclodextrins described in a patent. If 501 is a cyclodextrin entrained resveratrol, then 5 grams of 501 would be about 1 gram of resveratrol, and 4 grams of cyclodextrin, if it's a 1:1 complex. Is it now a factor of 4 they're claiming? When the 501 info first appeared, I seem to recall a factor of 7-10... something like that. If it were a factor of 4 and 5 grams of 501 was really only 1 gram of resveratrol, (all speculation on my part) then that would put the dose of plain old resveratrol at 4 grams, and Everclear/Miralax brew at who knows what?

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#9 maxwatt

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Posted 15 November 2007 - 11:55 AM

Also in the presentation I cited above, are statements that resveratrol bioavailability in humans is too low to make it practical to administer as a drug. More than two or three capsules a day means "low compliance". I find that their claim SRT501 is four times as potent as resveratrol, and they are doing trials at 5 grams a day, means that to see dramatic effects with non-micronized 99% powder, will require at least 15 grams. Not practical as a commercial product, except for fanatics like some of us.

Do we have any solid information regarding what exactly is in SRT501 besides resveratrol? I think Tween 80 was mentioned in some presentation, and there was a process using cyclodextrins described in a patent. If 501 is a cyclodextrin entrained resveratrol, then 5 grams of 501 would be about 1 gram of resveratrol, and 4 grams of cyclodextrin, if it's a 1:1 complex. Is it now a factor of 4 they're claiming? When the 501 info first appeared, I seem to recall a factor of 7-10... something like that. If it were a factor of 4 and 5 grams of 501 was really only 1 gram of resveratrol, (all speculation on my part) then that would put the dose of plain old resveratrol at 4 grams, and Everclear/Miralax brew at who knows what?


Everclear/miralax|lecithin would be equivalent to 5 grams. Dissolving in ethanol effictively micronizes it. I think it's 5 grams of resveratrol in the administered complex. We think it's tween80, not cyclodextrine (both were mentioned in the patent) because a reporter described SRT501 that he was given to taste when he was interviewing Sinclair et al. Both color and taste matched a tween80 mixture according to some of us who claimed to know tween80. This was in the early days of the 500mg resveratrol thread.




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