• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo

Product B - Telomerase Activation


  • Please log in to reply
602 replies to this topic

#361 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 18 January 2012 - 08:08 PM

I believe they use Astragaloside IV, what we used back in 2008.

They also state telomere support, rather than telomerase activation.

Hey, but you must know that regular vitamins mentioned in the women study I linked to above (some posts up), would also qualify as "telomere support"...

Cheers
A

#362 hav

  • Guest
  • 1,089 posts
  • 219
  • Location:Cape Cod, MA
  • NO

Posted 18 January 2012 - 08:12 PM

Stem Cell 100 has a web page that lists its contents.  Looks similar in thrust to Product B in that it combines a telomerase activator (Astragalus in this case) with a resveratrol-related compound and other antioxidants.  My personal concern is that that combination might nullify or weaken telomerase activation. But it might be healthy none the less. The charts on the same page suggest that it is beneficial to the life of fruit flies, but I'm not clear on whether that's a scientific study that's been exposed to peer review or not.  It's also not clear how they administered the product to the fruit flies, what amount they gave them, or how that amount relates to the dosage they recommend to humans.  And they don't indicate the proportions or purity of each ingredient in their product... only the total weight of mixture.

Howard

Edited by hav, 18 January 2012 - 08:19 PM.


sponsored ad

  • Advert
Adverts help to support LongeCity's non-profit work. To go ad-free join as Member.

#363 Louis

  • Guest
  • 143 posts
  • 8
  • Location:Boston MA

Posted 18 January 2012 - 09:03 PM

Anthony or anyone,

Do you know anything about Telomere Biosciences Product and Stem Cell 100?


I take Stem Cell 100 everyday and highly recommend it.
It was formulated by Bryant Villeponteau, the first inventor on Geron's hTERT patent.

Bryant is generally credited as the primary discoverer of the human telomerase gene (Bill Andrews led the team).
Hence his first inventor status on the patent.

#364 Louis

  • Guest
  • 143 posts
  • 8
  • Location:Boston MA

Posted 18 January 2012 - 09:21 PM

Anthony, I was gonna ask if your proclamations about Product B were long term or just until you start selling it. But, I guess their marketing approach won't allow that. I really don't want to get into a pissin war with you because you have enough of those going on in these forums already. Your motives are laughingly transparent. Yes, yes, I know, you really just want to sell "the best gosh darn product on the planet".


Sierra Sciences tested the exact product that Anthony sold called "Astral Fruit", which he claimed activated telomerase.
Astral Fruit had NO telomerase activity in the Sierra Sciences screens.

Anthony is well aware of this: This is the real source of his animosity towards Bill Andrews.

It's no coincidence that he has since mysteriously stopped selling Astral Fruit.
Instead, he has now started selling the competing product which he bad mouthed on this forum for years, TA-65.

The MLM marketing model would not allow Anthony to make any money by selling Product B.

Why would someone buy Product B from Anthony at retail prices when they can instead sign up as an independent distributor in 30 seconds with Isagenix and buy it at wholesale prices.

Make no mistake about it. Anthony uses this site as a vehicle to sell his products.
  • dislike x 1

#365 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 18 January 2012 - 10:52 PM

Sierra Sciences tested the exact product that Anthony sold called "Astral Fruit", which he claimed activated telomerase.

Astral Fruit had NO telomerase activity in the Sierra Sciences screens.

Anthony is well aware of this: This is the real source of his animosity towards Bill Andrews.


Hi Louis,

That sounds desperate. But let me help educate you a bit... Now did you really see the link you provided from Dr Valenzuela? Post #335

Here it is again:
http://www.jimmunol....Abstracts/90.30

He was testing the Cycloastragenol we provided him that we used in our Astral Fruit-C product. Where else do you think he got Cycloastragenol for his tests?

That's right, RevGenetics provided it free of charge.

Now either you are lying because I have never heard Bill Andrews say he tested Astral Fruit-C, or Bill Andrews super special screening procedure doesn't work well with Cycloastragenol (and of course who can verify it since only his lab does it?), or UCLA's standard methods (that Rita developed and Geron trusts so much) are wrong when it comes to Cycloastragenol.

So which is it Louis?

As far as I can tell, Bill Andrews information on his telomerase tests for cycloastragenol has never been peer reviewed, while Rita's and Valenzuela's have.

I think I would even trust Bryant more than Bill Andrews when it comes to lab results and research... you even stated this about Bryant and Bill:

Bryant is generally credited as the primary discoverer of the human telomerase gene (Bill Andrews led the team). Hence his first inventor status on the patent.


Heck that says quite a lot to me regarding bench work! In my personal opinion, leading a team is one thing... actually being the expert at bench work is a whole different story isn't it? Hey, I don't do my accountants job, but I lead the company... are you going to trust me to do your accounting?

A

Edited by Anthony_Loera, 18 January 2012 - 11:01 PM.


#366 Louis

  • Guest
  • 143 posts
  • 8
  • Location:Boston MA

Posted 18 January 2012 - 10:59 PM

Anthony or anyone,

Do you know anything about Telomere Biosciences Product and Stem Cell 100?


I take Stem Cell 100 everyday and highly recommend it.
It was formulated by Bryant Villeponteau, the first inventor on Geron's hTERT patent.

Bryant is generally credited as the primary discoverer of the human telomerase gene (Bill Andrews led the team).
Hence his first inventor status on the patent.


I should qualify this statement a little to be strictly correct scientifically:
Villeponteau is considered the principle discoverer of the RNA component of human telomerase. His name is first on this Geron patent. (This won him the inventor of the year award which he shared with Andrews and Funk and a fourth name I can't remember.)
He was also very highly involved in Geron work on the protein component of telomerase, which came later on after the RNA component was discovered.

#367 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 18 January 2012 - 11:02 PM

Fine but you still haven't answered the rest of my post:

Hi Louis,

That sounds desperate. But let me help educate you a bit... Now did you really see the link you provided from Dr Valenzuela?Post #335

Here it is again:
http://www.jimmunol....Abstracts/90.30

He was testing the Cycloastragenol we provided him that we used in our Astral Fruit-C product. Where else do you think he got Cycloastragenol for his tests?

That's right, RevGenetics provided it free of charge.

Now either you are lying because I have never heard Bill Andrews say he tested Astral Fruit-C, or Bill Andrews super special screening procedure doesn't work well with Cycloastragenol (and of course who can verify it since only his lab does it?), or UCLA's standard methods (that Rita developed and Geron trusts so much) are wrong when it comes to Cycloastragenol.

So which is it Louis?

A

#368 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 18 January 2012 - 11:08 PM

Again....As far as I can tell, Bill Andrews information on his telomerase tests for cycloastragenol has never been peer reviewed, while Rita's and Valenzuela's have.






A

#369 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 18 January 2012 - 11:30 PM

You know Louis,

I keep reading this below and at 10 Caps a day... that's over 300 pills a Month! That is what... Almost $250?! That is more expensive than TA-65 now eh?

Bill Andrews now takes 10 caps per day of Product B.

He mentions his product B dose increase in the same public January 11 conference call I referred to earlier.


So what is the excuse to buy this product over TA-65 now? They can't even say it's a telomerase activator in an associates marketing!


Now this below gives me hope... they are doing studies using a product that is not yet available to Isagenix associates? Well, why not use the original one we tested? Sounds like my big mouth is making them change things for the benefit of their customers, doesn't it?

This is the same call where they disclosed their discovery of natural compounds at roughly 6% of HeLa -- to be included in product B release #3. They'll also be using the new release #3 in the Maria Blasco clinical trial which is about to start (as opposed to release #2 currently on the market).


Well, I hope it works.

Let me know when I can order release #3, to test that one.

A

Edited by Anthony_Loera, 18 January 2012 - 11:32 PM.


#370 Louis

  • Guest
  • 143 posts
  • 8
  • Location:Boston MA

Posted 18 January 2012 - 11:34 PM

Folks, you don't have to take my word for it.

You can listen to Dave Woynarowski (author of the book referred to earlier, The Immortality Edge) make the same exact statement here:


Between minutes 4:45 and 5:45 of this video, Woynarowski states that Sierra Sciences tested Astral Fruit and it did NOT show any telomerase activity in their screens.

Anthony is well aware of this information. He is playing games.

#371 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 18 January 2012 - 11:41 PM

Actually I never have seen this video. However in it, Dave...sent everything to Bill Andrews for testing... I don't see any peer reviewed studies.

Astral Fruit-C had Cycloastragenol...

So here we go again:
From Dr Valenzuela?Post #335

Here it is again:
http://www.jimmunol....Abstracts/90.30

He was testing the Cycloastragenol we provided him that we used in our Astral Fruit-C product. Where else do you think he got Cycloastragenol for his tests?

That's right, RevGenetics provided it free of charge.

Now , it seems like we have narrowed it down a bit... at least we can say that it wasn't you who was lying, but the same applies....

Either Dave was lying, or Bill Andrews super special screening procedure doesn't work well with Cycloastragenol (and of course who can verify it since only his lab does it?), or UCLA's standard methods (that Rita developed and Geron trusts so much) are wrong when it comes to Cycloastragenol.

Again...So which is it Louis?

Here goes again....As far as I can tell, Bill Andrews information on his telomerase tests for cycloastragenol has never been peer reviewed, while Rita's and Valenzuela's have.

A

Edited by Anthony_Loera, 18 January 2012 - 11:44 PM.


#372 AdamI

  • Guest
  • 221 posts
  • 4
  • Location:Oslo

Posted 18 January 2012 - 11:50 PM

Stem Cell 100 has a web page that lists its contents. Looks similar in thrust to Product B in that it combines a telomerase activator (Astragalus in this case) with a resveratrol-related compound and other antioxidants. My personal concern is that that combination might nullify or weaken telomerase activation. But it might be healthy none the less. The charts on the same page suggest that it is beneficial to the life of fruit flies, but I'm not clear on whether that's a scientific study that's been exposed to peer review or not. It's also not clear how they administered the product to the fruit flies, what amount they gave them, or how that amount relates to the dosage they recommend to humans. And they don't indicate the proportions or purity of each ingredient in their product... only the total weight of mixture.

Howard


From stem cell 100 hompage: Stem Cell 100 increases telomerase activity in stem cells via the resveratrol analog pterostilbene, which is a major active component in Stem Cell 100. Pterostilbene is a highly potent natural analog of resveratrol with greatly improved oral adsorption and metabolic stability with better activity levels. Resveratrol has been shown to activate telomerase in human adult stem cells in independent studies.

Anything you tested as well Anthony?
That interview you posted link on Louis, he never mention Stem Cell 100... You know that guys opinion about that?
Just quite strange he only says TA-65 works, he is not promoting it maybe? And want to dismiss competotors you think?

A few "?" marks:)

#373 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 18 January 2012 - 11:51 PM

I am actually surprised he said astragenol doesn't activate telomerase either, while Geron has it as one!!

He is really relying on Bill's testing to say all this without peer reviewed studies?
Wow, pretty amazing.

Well if he sell's TA-65 exclusively, it's certainly possible he wants to promote it, right? Interesting.

A

Edited by Anthony_Loera, 18 January 2012 - 11:54 PM.


#374 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 19 January 2012 - 12:03 AM

From stem cell 100 hompage: Stem Cell 100 increases telomerase activity in stem cells via the resveratrol analog pterostilbene, which is a major active component in Stem Cell 100. Pterostilbene is a highly potent natural analog of resveratrol with greatly improved oral adsorption and metabolic stability with better activity levels. Resveratrol has been shown to activate telomerase in human adult stem cells in independent studies.

Anything you tested as well Anthony?
That interview you posted link on Louis, he never mention Stem Cell 100... You know that guys opinion about that?
Just quite strange he only says TA-65 works, he is not promoting it maybe? And want to dismiss competotors you think?

A few "?" marks:)


Great question Adaml, I still believe the Jury is out regarding resveratrol and telomerase... but I have some info from our latest newsletter that I believe may be interesting about resveratrol-Sirt-1 & the Telomerase protein:
http://us2.campaign-...2&id=b1ad1727d8

Resveratrol DNA, what?
First, In 2008 a group of scientists published the observation that human fibroblast cells artificially made to express more SIRT-1 delayed the onset of aging in those cells. SIRT-1 is a protein that can modify and therefore regulate DNA. Fast forward to the present: In what is very exciting news, in an article accepted but yet to be published, a group from Japan led by Yoshinori Katakura has repeated some of those experimental observations but very importantly added a potential explanation for the mechanisms for the delay in aging in human fibroblast cells (Biochemical and Biophysical Research Communications, 2011). It was demonstrated for the first time in fibroblast cells, that the extra SIRT-1 protein present in the cells caused specific RNA needed for telomerase protein to be made. In essence these authors conclude that the extra SIRT-1 protein induced by resveratrol (and by other methods) leads to more telomerase protein being made.


Adaml or Hav, want to take a gander at that study and see if this would certainly suggest taking micronized resveratrol 90 minutes prior to any telomerase activator to help produce additional SIRT-1... to support an increase in the telomerase protein when telomerase is activated?

Edited by Anthony_Loera, 19 January 2012 - 12:05 AM.


#375 Louis

  • Guest
  • 143 posts
  • 8
  • Location:Boston MA

Posted 19 January 2012 - 12:05 AM

Two outside labs have now confirmed the telomerase activity of product B Anthony. On January 11, Isagenix held a conference call open to the public where they anounced that the results have been independently confirmed in 2 independent studies. Bill Andrews was on the call and did a lot of the speaking. You can find recordings on the web. Of course, this all remains completely unpublished to date, just like your study.

They also announced that they have now found natural compounds that test at 6% of HeLa and that these will be available in the 3rd generation of product B, which will be released in the future.


Louis, did they say which groups have confirmed the activity? Was it in a cell-based in vitro assay? Do you have any links to anything written about it?


No unfortunately not niner. But in the past they have relied on 3 groups for independent confirmation of their activators: Woody Wright and Jerry Shay at the University of Texas Southwestern, Judy Campisi at Berkeley Labs, and Richard Allsopp at the University of Hawaii. Four of the biggest names in the field. My assumption is that it's some subset of these 3 labs. Possibly also including the Blasco lab. They have working relationships with all 4 of these labs.

They weren't shy about giving out the names of the labs that confirmed the telomerase activating activity of their patented synthetic C0057684, so I'm sure it's just a matter of time before we get the names in the case of Product B.

#376 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 19 January 2012 - 12:07 AM

Louis... don't avoid this post... I am waiting my friend, for an answer:

Actually I never have seen this video. However in it, Dave...sent everything to Bill Andrews for testing... I don't see any peer reviewed studies.

Astral Fruit-C had Cycloastragenol...

So here we go again:
From Dr Valenzuela?Post #335

Here it is again:
http://www.jimmunol....Abstracts/90.30

He was testing the Cycloastragenol we provided him that we used in our Astral Fruit-C product. Where else do you think he got Cycloastragenol for his tests?

That's right, RevGenetics provided it free of charge.

Now , it seems like we have narrowed it down a bit... at least we can say that it wasn't you who was lying, but the same applies....

Either Dave was lying, or Bill Andrews super special screening procedure doesn't work well with Cycloastragenol (and of course who can verify it since only his lab does it?), or UCLA's standard methods (that Rita developed and Geron trusts so much) are wrong when it comes to Cycloastragenol.

Again...So which is it Louis?

Here goes again....As far as I can tell, Bill Andrews information on his telomerase tests for cycloastragenol has never been peer reviewed, while Rita's and Valenzuela's have.

A


  • dislike x 1

#377 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 19 January 2012 - 12:13 AM

No unfortunately not niner. But in the past they have relied on 3 groups for independent confirmation of their activators: Woody Wright and Jerry Shay at the University of Texas Southwestern, Judy Campisi at Berkeley Labs, and Richard Allsopp at the University of Hawaii. Four of the biggest names in the field. My assumption is that it's some subset of these 3 labs. Possibly also including the Blasco lab. They have working relationships with all 4 of these labs.

They weren't shy about giving out the names of the labs that confirmed the telomerase activating activity of their patented synthetic C0057684, so I'm sure it's just a matter of time before we get the names in the case of Product B.


Did they say which version of Product B they tested? Version1, 2 or 3?
For all we know they tested the version that is not available to the public.

We ourselves had 3 versions of Astral Fruit...

so to limit confusion, it becomes a bit important to know which one we are talking about.

A

Edited by Anthony_Loera, 19 January 2012 - 12:14 AM.


#378 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 19 January 2012 - 12:18 AM

You know Louis,

I keep reading this below and at 10 Caps a day... that's over 300 pills a Month! That is what... Almost $250?! That is more expensive than TA-65 now eh?

Bill Andrews now takes 10 caps per day of Product B.

He mentions his product B dose increase in the same public January 11 conference call I referred to earlier.


So what is the excuse to buy this product over TA-65 now? They can't even say it's a telomerase activator in an associates marketing!


Wow... I keep on thinking about the 300 capsules a month...and the increaed Product B price...

I can't help it... it's a stunning number of capsules.

A
  • dislike x 1

#379 Louis

  • Guest
  • 143 posts
  • 8
  • Location:Boston MA

Posted 19 January 2012 - 12:31 AM

Actually I never have seen this video. However in it, Dave...sent everything to Bill Andrews for testing... I don't see any peer reviewed studies.

Either Dave was lying, or Bill Andrews super special screening procedure doesn't work well with Cycloastragenol (and of course who can verify it since only his lab does it?), or UCLA's standard methods (that Rita developed and Geron trusts so much) are wrong when it comes to Cycloastragenol.

Again...So which is it Louis?


All I can do is give you my scientific opinion:

I believe cycloastragenol will weakly activate telomerase in vitro in the specific immune cell line that Effros/Harley tested it with in their published paper.

However, I believe that the Sierra Sciences screen has clearly demonstrated that it will NOT work in fibroblasts. My personal opinion is that the fibroblast test is far more representative of the somatic cell lines in the human body.

There is a specific reason that Sierra Sciences ONLY uses fibroblasts in their screens. Their fibroblasts are absolutely incapable of activating telomerase on their own. The only know way to do it is via small-molecule interaction with the hTERT repressor.

Immune cells have their own internal mechanisms that allow them to very weakly activate telomerase on their own in response to cytokine stress (e.g. an infection). This introduces a major confounding variable into the experiment. Any compund in question could easy be activating this other machinery in the immune cell rather than directly acting on the hTERT repressor. There's no good way to tell. The other machinery is very poorly understood: Who knows how many different ways there are to activate it? No one. The 2 mechanisms are unrelated, and the first mechanism would only work in immune cells.

I do not believe cycloastragenol is capable of activating telomerase in fibroblasts, and therefore in the majority of somatic cell lines in the human body. I believe it is a promising telomerase activateing compound only in the context of immunology research. I trust the Sierra Sciences screen much more because it is fibroblast based.

#380 Louis

  • Guest
  • 143 posts
  • 8
  • Location:Boston MA

Posted 19 January 2012 - 12:37 AM

No unfortunately not niner. But in the past they have relied on 3 groups for independent confirmation of their activators: Woody Wright and Jerry Shay at the University of Texas Southwestern, Judy Campisi at Berkeley Labs, and Richard Allsopp at the University of Hawaii. Four of the biggest names in the field. My assumption is that it's some subset of these 3 labs. Possibly also including the Blasco lab. They have working relationships with all 4 of these labs.

They weren't shy about giving out the names of the labs that confirmed the telomerase activating activity of their patented synthetic C0057684, so I'm sure it's just a matter of time before we get the names in the case of Product B.


Did they say which version of Product B they tested? Version1, 2 or 3?
For all we know they tested the version that is not available to the public.


No, it could have been any version.

#381 Anthony_Loera

  • Life Member
  • 3,169 posts
  • 748
  • Location:Miami Florida

Posted 19 January 2012 - 01:39 AM

All I can do is give you my scientific opinion:

I believe cycloastragenol will weakly activate telomerase in vitro in the specific immune cell line that Effros/Harley tested it with in their published paper.

However, I believe that the Sierra Sciences screen has clearly demonstrated that it will NOT work in fibroblasts. My personal opinion is that the fibroblast test is far more representative of the somatic cell lines in the human body.

There is a specific reason that Sierra Sciences ONLY uses fibroblasts in their screens. Their fibroblasts are absolutely incapable of activating telomerase on their own. The only know way to do it is via small-molecule interaction with the hTERT repressor.

Immune cells have their own internal mechanisms that allow them to very weakly activate telomerase on their own in response to cytokine stress (e.g. an infection). This introduces a major confounding variable into the experiment. Any compund in question could easy be activating this other machinery in the immune cell rather than directly acting on the hTERT repressor. There's no good way to tell. The other machinery is very poorly understood: Who knows how many different ways there are to activate it? No one. The 2 mechanisms are unrelated, and the first mechanism would only work in immune cells.

I do not believe cycloastragenol is capable of activating telomerase in fibroblasts, and therefore in the majority of somatic cell lines in the human body. I believe it is a promising telomerase activateing compound only in the context of immunology research. I trust the Sierra Sciences screen much more because it is fibroblast based.


That my friend, was a great answer.

However, I am not convinced until I see a peer reviewed study that shows Product B activating fibroblasts, and one showing it's effect (or not) in immune cells.

For now, we have neither, while there is at least some data for TA-65 and Cycloastragenol.

For the sake of argument let's say Product B activates fibroblasts, but could not activate telomerase in immune cells, while TA-65 activated immune cells, but not fibroblasts...

Which would you prefer?

A

#382 Louis

  • Guest
  • 143 posts
  • 8
  • Location:Boston MA

Posted 19 January 2012 - 03:09 AM

> For the sake of argument let's say Product B activates fibroblasts, but could not activate telomerase in immune cells, while TA-65 activated immune cells, but not fibroblasts...

> Which would you prefer?

The best strategy in such a case would be to take both, which is exactly what Andrews is doing. That covers all bases.

But Andrews has gone on public record in the past and stated that Sierra Sciences has tested TA-65 and that it does very weakly activate telomerase in their fibroblast screens. (Despite his more recent ambiguous answers to this question.)

It's cycloastragenol that's in question here.
Despite the fact that they test out very close on mass spect, there still appear to be some important differences.

#383 Louis

  • Guest
  • 143 posts
  • 8
  • Location:Boston MA

Posted 19 January 2012 - 03:18 AM

It all may just come down to abilty of the various compounds to find their way into the cell and into the nucleus -- the bioavailability in vitro.
Certain compounds may more easily penetrate CD4 and CD8 T-cells than the particular fibroblast cell lines that Sierra uses, or vice-versa.

That's probably the simplest explanation for differences in the tests.

If in fact TA-65 is just a more absorbable form of cycloastragenol like you suggested earlier Anthony, e.g. microionized, that could explain why TA-65 would test very weakly positive in Sierra fibroblasts while bulk cycloastragenol shows no activity at all. In one case, a little TA-65 gets in. In the other, no cycloastragenol gets in. It may be that simple.

Same argument for the differences in the product B tests.

Edited by Louis, 19 January 2012 - 03:20 AM.


#384 Louis

  • Guest
  • 143 posts
  • 8
  • Location:Boston MA

Posted 19 January 2012 - 03:53 AM

Actually I never have seen this video. However in it, Dave...sent everything to Bill Andrews for testing... I don't see any peer reviewed studies.

Either Dave was lying, or Bill Andrews super special screening procedure doesn't work well with Cycloastragenol (and of course who can verify it since only his lab does it?), or UCLA's standard methods (that Rita developed and Geron trusts so much) are wrong when it comes to Cycloastragenol.

Again...So which is it Louis?


All I can do is give you my scientific opinion:

I believe cycloastragenol will weakly activate telomerase in vitro in the specific immune cell line that Effros/Harley tested it with in their published paper.

However, I believe that the Sierra Sciences screen has clearly demonstrated that it will NOT work in fibroblasts. My personal opinion is that the fibroblast test is far more representative of the somatic cell lines in the human body.

There is a specific reason that Sierra Sciences ONLY uses fibroblasts in their screens. Their fibroblasts are absolutely incapable of activating telomerase on their own. The only know way to do it is via small-molecule interaction with the hTERT repressor.

Immune cells have their own internal mechanisms that allow them to very weakly activate telomerase on their own in response to cytokine stress (e.g. an infection). This introduces a major confounding variable into the experiment. Any compund in question could easy be activating this other machinery in the immune cell rather than directly acting on the hTERT repressor. There's no good way to tell. The other machinery is very poorly understood: Who knows how many different ways there are to activate it? No one. The 2 mechanisms are unrelated, and the first mechanism would only work in immune cells.

I do not believe cycloastragenol is capable of activating telomerase in fibroblasts, and therefore in the majority of somatic cell lines in the human body. I believe it is a promising telomerase activateing compound only in the context of immunology research. I trust the Sierra Sciences screen much more because it is fibroblast based.


Well...It looks like I spoke too soon.
I now need to revise this opinion based on a brand new paper that I just became aware of.

It looks like Cal Harley just published a paper this past November that proves that both cycloastragenol and astragoloside IV do in fact activate telomerase in human embyonic kidney fibroblasts. To my knowledge, this is the first journal paper that shows cyclo or a-IV activate telomerase in non-immune cell lines.

http://www.ncbi.nlm....pubmed/22083896

If you read the full paper, which I recommend doing:

It seems that they've now discovered the actual mechanism by which cyclo and a-IV modulate the expression of hTERT. Both compounds operate indirectly by phosphorylating ERK, which then in turn operates on hTERT by a natural mechanism already present in the cells. It's pretty clear from the paper that they haven't yet figured out the exact details on how phosphorylating ERK leads to hTERT expression (although they lay out a rough sketch of how they think it may work), but they've pretty much proven that phosphorylating ERK is the key first step in how cyclo and a-IV work.

They then go on to show that cyclo and a-IV can phosphorylate ERK to varying degrees in a wide variety of cell types. But they only prove telomerase activation in kidney cells.

After reading this paper, I now believe it's reasonable to conclude that cyclo or a-IV may activate telomerase in any cell line where they are capable of phosphorylating ERK. That's definitely the case in CD4 and CD8 T-cells, for example. And apparently in embryonic kidney fibroblasts.

I think this definitely broadens the range of cell types over which cyclo or a-IV should in theory work -- now including various fibroblast lines in which cyclo or a-IV are capable of phosphorylating ERK.
  • like x 1

#385 niner

  • Guest
  • 16,276 posts
  • 1,999
  • Location:Philadelphia

Posted 19 January 2012 - 04:30 AM

But Andrews has gone on public record in the past and stated that Sierra Sciences has tested TA-65 and that it does very weakly activate telomerase in their fibroblast screens. (Despite his more recent ambiguous answers to this question.)

It's cycloastragenol that's in question here.
Despite the fact that they test out very close on mass spect, there still appear to be some important differences.


Waitaminute... cycloastragenol and TA65 show a difference on mass spec? As in they are not structurally identical? The RevGenetics analysis was HPLC, wasn't it? The physical form, micronized or not, shouldn't matter in either MS, LC, or cell based assays, since it will be put into solution, probably in DMSO, in preparation for any of these.
  • like x 1

#386 mikeinnaples

  • Guest
  • 1,907 posts
  • 296
  • Location:Florida

Posted 19 January 2012 - 02:54 PM

The TA65 Analysis I have a copy of looks like this:

.27mg Astragaloside IV
<0.01mg Astragenol
5.44mg Cycloastragenol

via Anthony's test from AACL

Edited by mikeinnaples, 19 January 2012 - 02:56 PM.

  • like x 1

#387 hav

  • Guest
  • 1,089 posts
  • 219
  • Location:Cape Cod, MA
  • NO

Posted 19 January 2012 - 06:51 PM

...
Adaml or Hav, want to take a gander at that study and see if this would certainly suggest taking micronized resveratrol 90 minutes prior to any telomerase activator to help produce additional SIRT-1... to support an increase in the telomerase protein when telomerase is activated?


Thanks, Anthony. Is this the one you're referring to? Perhaps someone here might explain the significance of "the transcription of human telomerase reverse transcriptase gene" and how it relates to protecting or lengthening telomeres.

http://www.ncbi.nlm....pubmed/22197555

SIRT1 prevents replicative senescence of normal human umbilical cord fibroblast through potentiating the transcription of human telomerase reverse transcriptase gene.
Yamashita S, Ogawa K, Ikei T, Udono M, Fujiki T, Katakura Y.

Abstract
SIRT1, the mammalian homolog of sirtuins, has emerged as a mediator of the beneficial effects of calorie restriction. Among them, we focused on the SIRT1-induced prevention of cellular senescence, and tried to reveal the molecular mechanisms that define the effects of SIRT1. Firstly in this study, we observed that overexpression of SIRT1 resulted in the prevention of cellular senescence of normal human umbilical cord fibroblast HUC-F2 cells. Here, we focused on the human telomerase reverse transcriptase (hTERT) gene as a target of the SIRT1-induced prevention of cellular senescence. Results showed that SIRT1, SIRT1 activator, resveratrol, and SIRT1 activating condition, starved condition, increased the transcription of hTERT in HUC-F2 cells. Next, we found that SIRT1 increased hTERT transcription in a c-MYC-dependent manner, triggered the transcription of the c-MYC gene and increased the amount of c-MYC recruited to the hTERT promoter. Further, SIRT1 increased the transcriptional activation ability of c-MYC and correspondingly increased the amount of acetylated H4 histone at the hTERT promoter. All of these results indicated that SIRT1 activates hTERT transcription through the involvement of c-MYC, and suggested that this SIRT1-induced augmentation of hTERT transcription resulted in the extension of the cellular life span of HUC-F2 cells.



#388 niner

  • Guest
  • 16,276 posts
  • 1,999
  • Location:Philadelphia

Posted 19 January 2012 - 08:02 PM

Thanks, Anthony. Is this the one you're referring to? Perhaps someone here might explain the significance of "the transcription of human telomerase reverse transcriptase gene" and how it relates to protecting or lengthening telomeres.

http://www.ncbi.nlm....pubmed/22197555

SIRT1 prevents replicative senescence of normal human umbilical cord fibroblast through potentiating the transcription of human telomerase reverse transcriptase gene.
Yamashita S, Ogawa K, Ikei T, Udono M, Fujiki T, Katakura Y.

Abstract
SIRT1, the mammalian homolog of sirtuins, has emerged as a mediator of the beneficial effects of calorie restriction. Among them, we focused on the SIRT1-induced prevention of cellular senescence, and tried to reveal the molecular mechanisms that define the effects of SIRT1. Firstly in this study, we observed that overexpression of SIRT1 resulted in the prevention of cellular senescence of normal human umbilical cord fibroblast HUC-F2 cells. Here, we focused on the human telomerase reverse transcriptase (hTERT) gene as a target of the SIRT1-induced prevention of cellular senescence. Results showed that SIRT1, SIRT1 activator, resveratrol, and SIRT1 activating condition, starved condition, increased the transcription of hTERT in HUC-F2 cells. Next, we found that SIRT1 increased hTERT transcription in a c-MYC-dependent manner, triggered the transcription of the c-MYC gene and increased the amount of c-MYC recruited to the hTERT promoter. Further, SIRT1 increased the transcriptional activation ability of c-MYC and correspondingly increased the amount of acetylated H4 histone at the hTERT promoter. All of these results indicated that SIRT1 activates hTERT transcription through the involvement of c-MYC, and suggested that this SIRT1-induced augmentation of hTERT transcription resulted in the extension of the cellular life span of HUC-F2 cells.

Transcription means that an RNA copy of genomic DNA is being created. This report probably does not mean that taking resveratrol with lengthen your telomeres. You have to look at the dose they used in their in vitro system, and see if it's even possible to attain that level in vivo. Usually in this kind of study, it isn't.
  • like x 1

#389 hav

  • Guest
  • 1,089 posts
  • 219
  • Location:Cape Cod, MA
  • NO

Posted 19 January 2012 - 11:10 PM

Thanks, niner. I couldn't find a free full-text copy of the study. But I take it that in any case this might cut against the idea that resvertatrol might be a telomerase inhibiter or nullify telomerase activaters.

Howard

Edited by hav, 19 January 2012 - 11:13 PM.


sponsored ad

  • Advert
Adverts help to support LongeCity's non-profit work. To go ad-free join as Member.

#390 niner

  • Guest
  • 16,276 posts
  • 1,999
  • Location:Philadelphia

Posted 20 January 2012 - 01:12 AM

But I take it that in any case this might cut against the idea that resvertatrol might be a telomerase inhibiter or nullify telomerase activaters.


It might either promote or inhibit telomerase, depending on dose. That's how it acts toward apoptosis. It also might be neither, again depending on dose and whether or not the needed dose can actually be attained in vivo.
  • like x 1


16 user(s) are reading this topic

0 members, 16 guests, 0 anonymous users