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Why is Glaxo Waiting?


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#31 Ringostarr

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Posted 21 April 2009 - 08:19 PM

Or maybe Sirtris saw that resveratrol (by itself or mixed with other substances) was nearly as effective as the synthetic molecules (NCE's) and knowing that you can't patent resveratrol decided to get out. Let's face it, Glaxo is basing it huge purchase price on the NCE's as resveratrol is not patentable and resveratrol delivery and technology is increasing rapidly. In other words, maybe the NCE's are not needed?


i tried to include this point of view by commenting that they had a patent/product problem. i think it is a relevant issue especially given Sinclair's comments in his Nature journal article on xenohormetics whereby he notes that 1/3rd of the top 10 selling drugs are based on plants and are not really patentable NCEs.



Let's Hope that is what it is. Effective over the counter resveratrol based products will be cheaper and 'more available' to the general public.

#32 bluemoon

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Posted 22 April 2009 - 12:39 AM

Let's Hope that is what it is. Effective over the counter resveratrol based products will be cheaper and 'more available' to the general public.


Does that mean you think they will improve from what is available today? Sincair was taking Longevinex and then switched to his own. Any guess to whether it is SRT501 or SRT1702? Someone should disguise themself as a giant Japanese knotweed and go stake out his house.

If he is being straightforward, then the 60 Minutes interview reveals that he thinks everyone will see a great gain as future 90 year olds feel 60.

Click HERE to rent this advertising spot to support LongeCity (this will replace the google ad above).

#33 Ghostrider

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Posted 27 April 2009 - 04:25 AM

Let's Hope that is what it is. Effective over the counter resveratrol based products will be cheaper and 'more available' to the general public.


Does that mean you think they will improve from what is available today? Sincair was taking Longevinex and then switched to his own. Any guess to whether it is SRT501 or SRT1702? Someone should disguise themself as a giant Japanese knotweed and go stake out his house.

If he is being straightforward, then the 60 Minutes interview reveals that he thinks everyone will see a great gain as future 90 year olds feel 60.


Guys, stupid question, what are the benefits of SRT501 over resveratrol? I know it's more powerful, but are there any studies to indicate how it will benefit healthy people?

#34 maxwatt

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Posted 27 April 2009 - 11:25 AM

Let's Hope that is what it is. Effective over the counter resveratrol based products will be cheaper and 'more available' to the general public.


Does that mean you think they will improve from what is available today? Sincair was taking Longevinex and then switched to his own. Any guess to whether it is SRT501 or SRT1702? Someone should disguise themself as a giant Japanese knotweed and go stake out his house.

If he is being straightforward, then the 60 Minutes interview reveals that he thinks everyone will see a great gain as future 90 year olds feel 60.


Guys, stupid question, what are the benefits of SRT501 over resveratrol? I know it's more powerful, but are there any studies to indicate how it will benefit healthy people?


Their own testing showed higher blood serum levels were obtained, and some of us have measured similar results for similar formulations. To some extend higher doses can raise the blood serum levels, but a limit is reached for most of us at under a five gram dose.

#35 Anthony_Loera

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Posted 27 April 2009 - 01:14 PM

Let's Hope that is what it is. Effective over the counter resveratrol based products will be cheaper and 'more available' to the general public.


Does that mean you think they will improve from what is available today? Sincair was taking Longevinex and then switched to his own. Any guess to whether it is SRT501 or SRT1702? Someone should disguise themself as a giant Japanese knotweed and go stake out his house.

If he is being straightforward, then the 60 Minutes interview reveals that he thinks everyone will see a great gain as future 90 year olds feel 60.



Remember Dr. Sinclair was upset at the fact that this brand was using his name and linking him to that product, so it is possible he didn't use it at all and it is just marketing.

Until you get an email from Sinclair stating that he took it, I will consider it a simple marketing hoax.

Cheers
A

#36 Ringostarr

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Posted 27 April 2009 - 09:55 PM

Let's Hope that is what it is. Effective over the counter resveratrol based products will be cheaper and 'more available' to the general public.


Does that mean you think they will improve from what is available today? Sincair was taking Longevinex and then switched to his own. Any guess to whether it is SRT501 or SRT1702? Someone should disguise themself as a giant Japanese knotweed and go stake out his house.

If he is being straightforward, then the 60 Minutes interview reveals that he thinks everyone will see a great gain as future 90 year olds feel 60.


Guys, stupid question, what are the benefits of SRT501 over resveratrol? I know it's more powerful, but are there any studies to indicate how it will benefit healthy people?


Their own testing showed higher blood serum levels were obtained, and some of us have measured similar results for similar formulations. To some extend higher doses can raise the blood serum levels, but a limit is reached for most of us at under a five gram dose.


In order for Sirtris to get patent protection on srt-501 it has to be non obvious. If you can easily mimic what srt-501 is without much thought or research (as it sounds like you can), then maybe srt-501 won't get patent protection? As I understand it srt-501 is patent pending right now.
Check out this case study from the Harvard Business School - srt-501 could be sold as a dietary supplement right now. Kind of like the fish oil you get from the doctor. Big pharma keeping healthcare costs high as always...http://sirtrispharma.com/pdfs/living-healthier-longer.pdf

#37 bluemoon

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Posted 28 April 2009 - 06:26 AM

Remember Dr. Sinclair was upset at the fact that this brand was using his name and linking him to that product, so it is possible he didn't use it at all and it is just marketing.

Until you get an email from Sinclair stating that he took it, I will consider it a simple marketing hoax.

Cheers
A


Well, Sinclair was upset at Shaklee as well, despite giving a speech or two for them. Here is what I read from Feb 2007:

Nonetheless, he [Sinclair] keeps taking the prescription-free Longevinex according to an email attributed to him by Justin Loew, treasurer of the Immortality Institute... Last November (2006) Loew said in an online forum that Sinclair had emailed him: "I take 4 pills of Longevinex with bfast and 4 at dinner, but I don't recommend anyone else take any resveratrol pills until we know more." (that was when Longy was at 40mg per capsule, so about 300mg a day )

So.... The Immortality Insitute.... anyone heard of that? Anyone know Justin Loew?

Edited by Holmes, 28 April 2009 - 06:45 AM.


#38 bluemoon

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Posted 29 April 2009 - 03:55 AM

(I also think RevGenetics and maybe Nature's Way among others are probably as good, but there is the issue of quercetin, which I hear is cheap. I don't pretend to know which is best or if there is a best brand. )

#39 Anthony_Loera

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Posted 29 April 2009 - 02:05 PM

If you are looking for cheap Quercetin to add to your regimen, I always point people to iHerb.

It is always cheaper to buy the larger amounts of it separately, since most who do take it, take 500mg or more. 50mg or less, according to some gurus who love it, just doesn't cut it.

Cheers
A

#40 fatboy

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Posted 30 April 2009 - 04:07 AM

If you are looking for cheap Quercetin to add to your regimen, I always point people to iHerb.


Do you take it?

#41 Anthony_Loera

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Posted 30 April 2009 - 05:07 PM

Nope

A

#42 bluemoon

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Posted 01 May 2009 - 04:47 AM

Nope

A


I guess we have to wait a while longer to know if the combination of quercetin and resveratrol is a good blend. The U Wisconsin researcher who was on 60 Minutes said he thought it was a good synergy (but on a separate Longevinex commercial). It looks like some here don't agree. I hope we will know more in a year or two.

#43 Anthony_Loera

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Posted 01 May 2009 - 01:40 PM

It was a commercial wasn't it.

Again, iHerb for cheaper Quercetin if you take it (specially if you take 500mg or more)...

BTW: How many here take 500mg or more a day?

A

#44 bluemoon

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Posted 02 May 2009 - 04:01 AM

It was a commercial wasn't it.

A


Yes, but that is the U Wisconsin researcher, who was interviewed on 60 Minutes, saying that he thinks Longevinex provides a good synergy with resveratrol, quercetin and IP6. Some here say use quercetin, some say don't. He's a lead researcher in this field, so doesn't it make sense to consider that?

#45 Dmitri

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Posted 15 May 2009 - 03:36 AM

Let's Hope that is what it is. Effective over the counter resveratrol based products will be cheaper and 'more available' to the general public.


Does that mean you think they will improve from what is available today? Sincair was taking Longevinex and then switched to his own. Any guess to whether it is SRT501 or SRT1702? Someone should disguise themself as a giant Japanese knotweed and go stake out his house.

If he is being straightforward, then the 60 Minutes interview reveals that he thinks everyone will see a great gain as future 90 year olds feel 60.


Guys, stupid question, what are the benefits of SRT501 over resveratrol? I know it's more powerful, but are there any studies to indicate how it will benefit healthy people?


Their own testing showed higher blood serum levels were obtained, and some of us have measured similar results for similar formulations. To some extend higher doses can raise the blood serum levels, but a limit is reached for most of us at under a five gram dose.


Has anyone had the chance to read this article? It's from 2007 but it discusses the issue at hand:

http://www.npr.org/t...toryId=16727282

The new compounds are the property of Sirtris, a company that Sinclair helped start. Unlike with resveratrol, which occurs naturally and is sold as a dietary supplement, Sirtris will need FDA approval to market the compounds.

"We're moving away from this molecule in red wine toward real drug discovery, pharmaceutical and rational drug design that most of the drugs we take these days come from," Sinclair said.

And drugs have to be approved to treat a specific disease. So the new study took the most potent new compound and studied its effect on mice and rats with diabetes.

The researchers found that it controlled blood sugar as well as a widely used diabetes drug.

Sinclair believes the compound also will work against other diseases of aging, including cancer.

Less sure is Dr. Randall Holcombe, the chief of hematology and oncology at the University of California-Irvine. He did an experiment comparing pure resveratrol to a powder made from grapes. The goal was to reduce the risk of colon cancer.

"We actually found that the grape powder was more effective than pure resveratrol," Holcombe said, "and that suggested that resveratrol is more active in combination with other compounds such as grapes than it is all by itself."

Holcombe says that raises the possibility that Sinclair's super-resveratrol compounds, by themselves, won't do much to prevent cancer.


Any thoughts on what that other researcher found?

#46 maxwatt

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Posted 15 May 2009 - 04:27 AM

Let's Hope that is what it is. Effective over the counter resveratrol based products will be cheaper and 'more available' to the general public.


Does that mean you think they will improve from what is available today? Sincair was taking Longevinex and then switched to his own. Any guess to whether it is SRT501 or SRT1702? Someone should disguise themself as a giant Japanese knotweed and go stake out his house.

If he is being straightforward, then the 60 Minutes interview reveals that he thinks everyone will see a great gain as future 90 year olds feel 60.


Guys, stupid question, what are the benefits of SRT501 over resveratrol? I know it's more powerful, but are there any studies to indicate how it will benefit healthy people?


Their own testing showed higher blood serum levels were obtained, and some of us have measured similar results for similar formulations. To some extend higher doses can raise the blood serum levels, but a limit is reached for most of us at under a five gram dose.


Has anyone had the chance to read this article? It's from 2007 but it discusses the issue at hand:

http://www.npr.org/t...toryId=16727282

The new compounds are the property of Sirtris, a company that Sinclair helped start. Unlike with resveratrol, which occurs naturally and is sold as a dietary supplement, Sirtris will need FDA approval to market the compounds.

"We're moving away from this molecule in red wine toward real drug discovery, pharmaceutical and rational drug design that most of the drugs we take these days come from," Sinclair said.

And drugs have to be approved to treat a specific disease. So the new study took the most potent new compound and studied its effect on mice and rats with diabetes.

The researchers found that it controlled blood sugar as well as a widely used diabetes drug.

Sinclair believes the compound also will work against other diseases of aging, including cancer.

Less sure is Dr. Randall Holcombe, the chief of hematology and oncology at the University of California-Irvine. He did an experiment comparing pure resveratrol to a powder made from grapes. The goal was to reduce the risk of colon cancer.

"We actually found that the grape powder was more effective than pure resveratrol," Holcombe said, "and that suggested that resveratrol is more active in combination with other compounds such as grapes than it is all by itself."

Holcombe says that raises the possibility that Sinclair's super-resveratrol compounds, by themselves, won't do much to prevent cancer.


Any thoughts on what that other researcher found?


The best we can do is half-assed guesses, as there is far to little information available.

A little googling found THIS. "The first two patients receiving resveratrol pills will be treated at a dose of 20mg/day, the third and fourth patients at a dose of 80mg/day and the fifth and sixth patients at a dose of 160mg/day."

and "Dietary Supplement: grapes - 1 pound of seedless red grapes" (and lesser amounts in different groups.).

Holcombe was working with colon cancer, and diet is well-known to be the greatest predictor of colon cancer. Certainly a pound of grapes has more fiber than any resveratrol supplement. The colon cancer preventive effects of high fiber diets are well known. Salad, beans, and fruit: eat these and you will not get colon cancer. It is possible the effect he was reporting would no be seen with other cancers, such as breast or lung or pancreatic. Fiber is useless there. And there could be many other explanations.

In one of his papers Holcombe did find that resveratrl acted on the Wnt pathway, which would inhibit cancer growth, systemically, not just in the gut.

#47 buck

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Posted 24 May 2009 - 07:48 PM

Two questions. If it is waiting FDA approval, are any of the supplements worthwhile currently? And, several articles I read said that it is essential that the supplement be of enteric coating or else stomach acid will defeat the purpose of taking it. Any answers? I am very new to the whole issue. Thanks for your patience.

Edited by buck, 24 May 2009 - 07:50 PM.


#48 nowayout

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Posted 24 May 2009 - 10:01 PM

Let's Hope that is what it is. Effective over the counter resveratrol based products will be cheaper and 'more available' to the general public.


Does that mean you think they will improve from what is available today? Sincair was taking Longevinex and then switched to his own. Any guess to whether it is SRT501 or SRT1702? Someone should disguise themself as a giant Japanese knotweed and go stake out his house.

If he is being straightforward, then the 60 Minutes interview reveals that he thinks everyone will see a great gain as future 90 year olds feel 60.


Guys, stupid question, what are the benefits of SRT501 over resveratrol? I know it's more powerful, but are there any studies to indicate how it will benefit healthy people?


Their own testing showed higher blood serum levels were obtained, and some of us have measured similar results for similar formulations. To some extend higher doses can raise the blood serum levels, but a limit is reached for most of us at under a five gram dose.


Higher serum levels would only be good if they are both safe and more effective for whatever desired health outcome. Is there any evidence that this is the case here, especially for life extension? After all, although baby aspirin is useful for life extension in some people, we won't really get excited about looking for substances that are 1000 times more potent than aspirin.

Edited by andre, 24 May 2009 - 10:01 PM.


#49 niner

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Posted 25 May 2009 - 03:21 AM

Two questions. If it is waiting FDA approval, are any of the supplements worthwhile currently? And, several articles I read said that it is essential that the supplement be of enteric coating or else stomach acid will defeat the purpose of taking it. Any answers? I am very new to the whole issue. Thanks for your patience.

A lot of people are already taking resveratrol, and find it to be useful. Resveratrol does not need to be enteric coated. There have been a number of pharmacokinetic studies in humans and other animals that showed resveratrol to be well absorbed without enteric coating.

#50 Dmitri

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Posted 25 May 2009 - 06:27 AM

Let's Hope that is what it is. Effective over the counter resveratrol based products will be cheaper and 'more available' to the general public.


Does that mean you think they will improve from what is available today? Sincair was taking Longevinex and then switched to his own. Any guess to whether it is SRT501 or SRT1702? Someone should disguise themself as a giant Japanese knotweed and go stake out his house.

If he is being straightforward, then the 60 Minutes interview reveals that he thinks everyone will see a great gain as future 90 year olds feel 60.


Guys, stupid question, what are the benefits of SRT501 over resveratrol? I know it's more powerful, but are there any studies to indicate how it will benefit healthy people?


Their own testing showed higher blood serum levels were obtained, and some of us have measured similar results for similar formulations. To some extend higher doses can raise the blood serum levels, but a limit is reached for most of us at under a five gram dose.


Higher serum levels would only be good if they are both safe and more effective for whatever desired health outcome. Is there any evidence that this is the case here, especially for life extension? After all, although baby aspirin is useful for life extension in some people, we won't really get excited about looking for substances that are 1000 times more potent than aspirin.


Do people here actually want to use this resveratrol drug? Interviews and articles that mention the drug allude to the fact that it will be used to treat diseases of aging such as cancer, diabetes and heart disease. So, why would any members here that are free of disease be waiting for this drug? Also, chances are doctors won't give you a prescription for it unless you are suffering from the diseases it is intended to treat?

#51 maxwatt

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Posted 25 May 2009 - 09:54 AM

Let's Hope that is what it is. Effective over the counter resveratrol based products will be cheaper and 'more available' to the general public.


Does that mean you think they will improve from what is available today? Sincair was taking Longevinex and then switched to his own. Any guess to whether it is SRT501 or SRT1702? Someone should disguise themself as a giant Japanese knotweed and go stake out his house.

If he is being straightforward, then the 60 Minutes interview reveals that he thinks everyone will see a great gain as future 90 year olds feel 60.


Guys, stupid question, what are the benefits of SRT501 over resveratrol? I know it's more powerful, but are there any studies to indicate how it will benefit healthy people?


Their own testing showed higher blood serum levels were obtained, and some of us have measured similar results for similar formulations. To some extend higher doses can raise the blood serum levels, but a limit is reached for most of us at under a five gram dose.


Higher serum levels would only be good if they are both safe and more effective for whatever desired health outcome. Is there any evidence that this is the case here, especially for life extension? After all, although baby aspirin is useful for life extension in some people, we won't really get excited about looking for substances that are 1000 times more potent than aspirin.


Do people here actually want to use this resveratrol drug? Interviews and articles that mention the drug allude to the fact that it will be used to treat diseases of aging such as cancer, diabetes and heart disease. So, why would any members here that are free of disease be waiting for this drug? Also, chances are doctors won't give you a prescription for it unless you are suffering from the diseases it is intended to treat?


Many people believe that such sirtuin agonists do not act directly against specific disease(s), but against the underlying cause, which is perhaps mitochondrial myopathies which develop with the passage of time. The best evidence to date has been Sinclair's mouse study, where normal diet mice were treated with resveratrol and/or EOD feeding, a putative form of CR. While the resveratrol group did not outlive the controls, they did not develop the diseases of aging seen in the controls: arthritis, heart problems, diabetes, frailty. One would think that if the experiment were repeated, perhaps with better living conditions for the mice, then some difference in life span might emerge; even if there were no life extension, the improvement in quality of life would be worth it. As my grandmother used to say, "an ounce of prevention is worth a pound of cure."

As for obtaining prescription drugs, there are many ways to get drugs without a prescription, or ways to get a doctor to give you a prescription.

But I would not wait for these drugs as some kind of golden bullet. If you look at the graphs in the Sinclair's paper on them, they did activate Sirt1 ten-fold over resveratrol, not a thousand fold as implied in press releases. BUT they were no more effective than resveratrol at activating the other six sirtuins, including those in the mitochondria.

As for the desirability of high serum levels, many in vitro studie shave shown a minimum concentration of resveratrol is necessary to obtain results, such as inducing apoptosis in certain kinds of cancer cells. Until it is demonstrated otherwise, one could infer that is is desirable to obtain the highest blood serum levels one can. Resveratrol has been shown to be unusually non-toxic, certainly much less so than aspirin. Published studies to date appear to have shown a definite dose-response relationship: the higher the dose, the stronger the benefit.

Edited by maxwatt, 25 May 2009 - 10:05 AM.


#52 nowayout

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Posted 25 May 2009 - 04:34 PM

Many people believe that such sirtuin agonists do not act directly against specific disease(s), but against the underlying cause, which is perhaps mitochondrial myopathies which develop with the passage of time. The best evidence to date has been Sinclair's mouse study, where normal diet mice were treated with resveratrol and/or EOD feeding, a putative form of CR. While the resveratrol group did not outlive the controls, they did not develop the diseases of aging seen in the controls: arthritis, heart problems, diabetes, frailty.


So what did they die of?

As for the desirability of high serum levels, many in vitro studie shave shown a minimum concentration of resveratrol is necessary to obtain results, such as inducing apoptosis in certain kinds of cancer cells. Until it is demonstrated otherwise, one could infer that is is desirable to obtain the highest blood serum levels one can.


One could infer that, but not in classical Aristotelian logic. :)

Resveratrol has been shown to be unusually non-toxic, certainly much less so than aspirin.


Except to the heart (cardiomyopathy at high doses) and perhaps anecdotally to the tendons.

#53 maxwatt

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Posted 26 May 2009 - 12:32 AM

Many people believe that such sirtuin agonists do not act directly against specific disease(s), but against the underlying cause, which is perhaps mitochondrial myopathies which develop with the passage of time. The best evidence to date has been Sinclair's mouse study, where normal diet mice were treated with resveratrol and/or EOD feeding, a putative form of CR. While the resveratrol group did not outlive the controls, they did not develop the diseases of aging seen in the controls: arthritis, heart problems, diabetes, frailty.


So what did they die of?

As for the desirability of high serum levels, many in vitro studie shave shown a minimum concentration of resveratrol is necessary to obtain results, such as inducing apoptosis in certain kinds of cancer cells. Until it is demonstrated otherwise, one could infer that is is desirable to obtain the highest blood serum levels one can.


One could infer that, but not in classical Aristotelian logic. :)

Resveratrol has been shown to be unusually non-toxic, certainly much less so than aspirin.


Except to the heart (cardiomyopathy at high doses) and perhaps anecdotally to the tendons.


Wrong on that last point. The study did not use resveratrol, but attempted to ascertain the effects of Sirt1, and stimulated its expression in heart muscle by increasing blood pressure; not surprising cardiomyopathy developed.

#54 biochemie

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Posted 02 June 2009 - 04:37 PM

Wrong on that last point. The study did not use resveratrol, but attempted to ascertain the effects of Sirt1, and stimulated its expression in heart muscle by increasing blood pressure; not surprising cardiomyopathy developed.


Thank you. I despise the spread of misinformation.

#55 Tim Jones

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Posted 19 June 2009 - 06:13 PM

I think it is also possible that they may have unpublished information on incidence of possible side effects that made them decide that the drug would indeed be unapprovable for the general population.


There is little doubt that there is a downside to any compound you take long term, including Resveratrol. We just need more time to see how bad its long term side effects are, but I can assure you that they are there somewhere. Also, I continue to notice people treating this compound as something extremely unique and special when it clearly is not. Many compounds work on SIRT1, and I can assure you that Dr. Sinclair knows this as well. Metformin, for example, is much more powerful when it comes to SIRT1, it also reduces glycogen in the liver resulting in very powerful weight loss, and is widely known to re sensitize a wide range of receptors especially in the hypothalamus. It also have been proven as well to extend life in several smaller mammals. Metformin's fatal flaw, however, is that its side effects are well understood, and that it has been been in use since the late 70's. I guess I should also mention that it also decreases the 3beta-hsd enzyme, which unfortunately reduces testosterone. This is great for women with PCOS, but would be a miserable experience for any male.

Personally, I think some perspective is in order... (Just my opinion, though) The near mythical focus on the CR models are quite baffling to me and many others. Most discoveries you see are typically revealed/validated in nature somewhere, but CR does not appear to be. If the CR pricinciple truly existed in an organism are complex as a homo sapien, then we should see wide deviations in the maximum global lifespan statistics data. If it is there, then at face value the data does not appear to show it. In fact, the maximum lifespan data is quite consistent even when you look in the past. For example, Ben Franklin lived to a rather impressive age of 84 with no access to modern day medical technologies whatsoever, or even a basic cholesterol screening for that matter. Meaning, you will have a hard time convincing the scientific community that the only seperating people in certain African regions from living 140+ years (instead of about 62 years now) is a couple multi-vitamins.

With that said, I equally enjoy the thought that we have discovered a compound that is the medical equivalent of the fountain of youth. It is exciting to think about, but the professional side of me realizes that biology is the most unforgiving science out there. What is more likely is that this mythical compound will help us manage aging ailments better, and hopefully will gain us a extra 5 to 7 year or something similar. Meaning, what you can deduce in mice in no way means that it applies to us...

Edited by Tim Jones, 19 June 2009 - 06:25 PM.


#56 seekonk

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Posted 19 June 2009 - 07:55 PM

With that said, I equally enjoy the thought that we have discovered a compound that is the medical equivalent of the fountain of youth. It is exciting to think about, but the professional side of me realizes that biology is the most unforgiving science out there. What is more likely is that this mythical compound will help us manage aging ailments better, and hopefully will gain us a extra 5 to 7 year or something similar. Meaning, what you can deduce in mice in no way means that it applies to us...


...which is all we have left to cling to, since resveratrol did not extend the maximal life spans of lean mice. I'm not sure what compound you are alluding to as a fountain of youth, since so far for mice, resveratrol is not it...

#57 maxwatt

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Posted 19 June 2009 - 08:52 PM

With that said, I equally enjoy the thought that we have discovered a compound that is the medical equivalent of the fountain of youth. It is exciting to think about, but the professional side of me realizes that biology is the most unforgiving science out there. What is more likely is that this mythical compound will help us manage aging ailments better, and hopefully will gain us a extra 5 to 7 year or something similar. Meaning, what you can deduce in mice in no way means that it applies to us...


...which is all we have left to cling to, since resveratrol did not extend the maximal life spans of lean mice. I'm not sure what compound you are alluding to as a fountain of youth, since so far for mice, resveratrol is not it...


but see this post -- the mice died of lymphoma caused by retrovirus so is suspect. and the resv mice were healthier in old age....

#58 seekonk

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Posted 19 June 2009 - 09:02 PM

...which is all we have left to cling to, since resveratrol did not extend the maximal life spans of lean mice. I'm not sure what compound you are alluding to as a fountain of youth, since so far for mice, resveratrol is not it...


but see this post -- the mice died of lymphoma caused by retrovirus so is suspect. and the resv mice were healthier in old age....


Yes, but lots of drugs will make you healthier in old age without improving maximal life span, so this is a pretty flimsy straw to cling to in the context of maximal life extension. But I agree that it would be nice to have other studies available in a species less genetically predisposed (endogenous retroviruses are part of the inherited genome) to cancer.

But even if we can find a species where this is the case, the results may be of questionable value. The human genome is known to contain several thousand endogenous retroviruses, some of which are implicated in human cancers and autoimmune diseases, so who knows, this mouse model might actually be a good model for (a significant subpopulation of) humans in this respect.

Here is a good source, full text available at http://www.pubmedcen...i?artid=1187282

Demystified . . . Human endogenous retrovirusesP N Nelson,1 P R Carnegie,2 J Martin,1 H Davari Ejtehadi,1 P Hooley,1 D Roden,1 S Rowland-Jones,3 P Warren,1 J Astley,1 and P G Murray4

Abstract

Human endogenous retroviruses (HERVs) are a family of viruses within our genome with similarities to present day exogenous retroviruses. HERVs have been inherited by successive generations and it is possible that some have conferred biological benefits. However, several HERVs have been implicated in certain cancers and autoimmune diseases. This article demystifies these retroviruses by providing an insight into HERVs, their means of classification, and a synopsis of HERVs implicated in cancer and autoimmunity. Furthermore, the biological roles of HERVs are explored.


HERVS AND CANCER

Although the precise role(s) of HERVs in the carcinogenic process has not been fully elucidated there are several studies that, if taken together, put forward a convincing argument for the possible involvement of HERVs in malignancy. HERVs may be involved in carcinogenesis by virtue of the expression of HERV mRNA,26 functional proteins,27 or retroviral-like particles.28 They may also be associated with the generation of new promoters29 or the activation of proto-oncogenes.30 The expression of HERV-R mRNA is increased in some cases of small cell lung carcinoma.26 In addition, a teratocarcinoma cell line has been shown to possess a HERV-K sequence and to secrete retroviral-like particles.28 Testicular germ cell tumours (TGCTs) have been shown to contain proteins of the HERV-K family and patients with TGCT often exhibit a specific immune response to gag and env proteins.27,31 It has been suggested that HERV-K may be important in the progression of TGCT through inhibition of an effective immune response,31 and the HERV env genes have been shown to encode immunosuppressive proteins.32,33 It is clear that overexpressed HERV proteins can elicit high titre IgG responses in some settings (for example, HERV-K10 in patients with renal cancer), as detected by the SEREX method (serological identification of expressed genes),34 suggesting that HERV proteins may in the future provide targets for antitumour immunotherapy.

"It has been suggested that HERV-K may be important in the progression of testicular germ cell tumours through inhibition of an effective immune response"

HERV-K might be important in the pathogenesis of human breast cancer. It has been shown that the T47D human mammary carcinoma cell line produces retroviral particles35 with reverse transcriptase activity.36 Both the HERV-K10 related sequences of T47D cells37 and the reverse transcriptase activity36 are increased by steroid hormone treatment, which is thought to be the result of transcriptional activation via binding of the progesterone receptor to regions on the HERV-K genome that correspond to progesterone and glucocorticoid response elements.In choriocarcinoma, it has been shown that a HERV type C is inserted into the human growth factor gene, pleiotrophin (PTN). This results in the generation of a novel tissue specific promoter, which results in the expression of HERV–PTN fusion transcripts, leading to the production of biologically active PTN protein. Expression of the PTN protein (which is normally expressed only at very low amounts in a few normal adult tissues38) appears to be responsible for the aggressive and invasive growth of human choriocarcinoma.29Overexpression is a common mechanism by which proto-oncogenes become activated, leading to subsequent neoplastic transformation.39 In particular, activation of proto-oncogenes of the ras family is common in many tumour types, and some studies have suggested a potential role for HERVs in ras activation. It was shown a methylnitrosourea induced rat mammary carcinoma that insertion of a defective endogenous retrovirus into the intron of c-Ha-ras was responsible for its more than 10 fold overexpression.30


HERVS AND AUTOIMMUNITY

In 1990, an article appeared in the Times newspaper (24 November) with the title "AIDS-like virus may cause arthritis". The report focused on Robert Garry's research that identified retroviral particles in lip biopsies taken from patients with primary Sjogren's syndrome (SS).41 Similarly, in other autoimmune rheumatic diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), a plethora of articles added to this intriguing observation by providing evidence of retroviral antigens at the site of disease, or the presence of antiretroviral antibodies in the sera of patients.6,42–44 A novel report in 1994 used both PCR (using consensus primers) and serological tests to investigate the presence of retroviruses in a cross section of patients with rheumatoid diseases, including RA, SS, and SLE.45 Interestingly, PCR failed to amplify products relating to HTLV-I or HIV-1, although antibodies to retroviral antigens were detected in the sera of patients. Consequently, there appeared to be a conundrum: antibodies to retroviral products were present but no evidence to implicate exogenous retroviruses could be found. Between 1996 and 1999, some research groups used so called "degenerate" retroviral primers in their PCR reactions.7,46,47 These primers cater for modest variations within two segments common to all retroviruses within the reverse transcriptase encoding pol region and provide an intervening "fingerprint region", which permits DNA sequencing. In brief, these studies7,46,47 revealed nucleotide homologies to endogenous retroviral families, including viruses with similarity to known exogenous retroviruses. Thus, it was plausible that the presence of HERVs could provide an explanation for the presence of antiretroviral antibodies in certain rheumatoid diseases.6,7,48 HERVs have also been implicated in other autoimmune diseases, such as multiple sclerosis (HERV-W, HERV-H) and insulin dependent diabetes mellitus (IDDM) (HERV-K, IDDM22), in addition to inflammatory vascular diseases.49–54 However, in the case of IDDM, subsequent studies55,56 have not been able to confirm this association. Mechanisms whereby HERVs could influence autoimmunity include molecular mimicry (HERVs sharing amino acids common to host proteins), superantigen motifs that bypass the normal MHC restrictive process of T cell stimulation, aberrant expression of antigens, and the presence of neo-antigens, perhaps as a result of HERV and/or exogenous viral combinations.7,32,57–59 The use of animal models has also served to enhance our understanding of endogenous retroviruses. In a lupus model, an 8.4 kbp endogenous retroviral transcript is expressed in affected mice.60 Furthermore, a retroviral element in one of the introns of the fas apoptosis gene appears to alter the splicing of fas transcripts, resulting in a lupus-like autoimmune disease in MRL-lpr/lpr mice.61 Further investigations using animal models and multicentre patient studies are needed to establish links between specific HERVs and autoimmune diseases because many HERVs are also expressed in varying amounts, or in a coordinated fashion, in normal tissues.62,63

"Mechanisms whereby HERVs could influence autoimmunity include molecular mimicry, superantigen motifs that bypass the normal MHC restrictive process of T cell stimulation, aberrant expression of antigens, and the presence of neo-antigens"


Edited by seekonk, 19 June 2009 - 09:21 PM.


#59 stephen_b

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Posted 19 June 2009 - 09:18 PM

There is little doubt that there is a downside to any compound you take long term, including Resveratrol.

Like water? That kind of statement is hard to back up.

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#60 niner

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Posted 20 June 2009 - 04:35 AM

Personally, I think some perspective is in order... (Just my opinion, though) The near mythical focus on the CR models are quite baffling to me and many others. Most discoveries you see are typically revealed/validated in nature somewhere, but CR does not appear to be. If the CR pricinciple truly existed in an organism are complex as a homo sapien, then we should see wide deviations in the maximum global lifespan statistics data. If it is there, then at face value the data does not appear to show it. In fact, the maximum lifespan data is quite consistent even when you look in the past. For example, Ben Franklin lived to a rather impressive age of 84 with no access to modern day medical technologies whatsoever, or even a basic cholesterol screening for that matter. Meaning, you will have a hard time convincing the scientific community that the only seperating people in certain African regions from living 140+ years (instead of about 62 years now) is a couple multi-vitamins.

The problem with this argument is that starvation is not CR. CR is difficult to do properly, and is more correctly called CRON, or Calorie Restriction with Optimal Nutrition. "A couple multi-vitamins" is not sufficient to turn a grossly inadequate diet to CRON. Further, I have never heard anyone in the CR community claim that they expected to live 140+ years. Of the billions of humans that have ever lived, the number who have practiced true CRON over a significant fraction of their lifespan is almost nil. Perspective is great, but elaborate straw-man arguments are not.

With that said, I equally enjoy the thought that we have discovered a compound that is the medical equivalent of the fountain of youth. It is exciting to think about, but the professional side of me realizes that biology is the most unforgiving science out there. What is more likely is that this mythical compound will help us manage aging ailments better, and hopefully will gain us a extra 5 to 7 year or something similar. Meaning, what you can deduce in mice in no way means that it applies to us...

And an extra 5 to 7 years can't even be deduced from mice, can it? Certainly not in maximal lifespan, not that I care about maxima. Given that the odds of my reaching the maximum human lifespan are vanishingly small, I am far more interested in compounds that increase the mean lifespan, which would have a passable chance of affecting me. I'm not ever sure that resveratrol will do that, although existing data suggest that it might.

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