602 replies to this topic

[Anthony_Loera]

If product B induces telomerase, and that telomerase is active, then the inhibition question is somewhat moot.

I Agree Niner,

I am hoping for the best on the results.
I would personally be happier if the darn Product B came out with great results, than if it didn't.

A

Edited by Anthony_Loera, 07 November 2011 - 04:20 AM.

[Hebbeh]

Is it possible that by expressing telomerase and therefore artificially prolonging the life of a cell, that we may also be prolonging the life of senescent cells allowing them to survive longer than they should and allowing them to subsequently poison healthy cells around them causing more harm than good?

[niner]

Is it possible that by expressing telomerase and therefore artificially prolonging the life of a cell, that we may also be prolonging the life of senescent cells allowing them to survive longer than they should and allowing them to subsequently poison healthy cells around them causing more harm than good?

That's a good question. If lengthening telomeres keeps cells from entering replicative senescence, there should be no problem. If a cell is genetically damaged as a result of short telomeres, then the telomeres are subsequently lengthened, would you then have a genetically injured cell that was again free to divide? I don't know. It might turn out to be the case that elderly people with a lot of senescent cells will first need a therapy that kills senescent cells before they get telomerase induction therapy. Today, the toolbox is pretty empty. We have the bare beginnings of a telomere extension therapy, but we don't yet appear to have a senescent cell removal method that's ready to use on humans. Now that we've seen the value of senescent cell elimination, a lot of people will probably start trying to develop ways to do that, or at least I hope someone will. I suspect that within a decade, we will have passable therapies for both of these things, and we will start answering questions like this.

[niner]

Resveratrol inhibits telomerase:
http://www.ncbi.nlm....pubmed/16465368
http://www.ncbi.nlm....pubmed/16918129

The first paper is available as full text, and I was able to find that they used a concentration of 88 uM in vitro in order to get significant telomerase inhibition. At a concentration of 44 uM, they described the inhibition as "marginal".

The second paper stated "relatively high concentrations of this compound were found to be able to substantially down-regulate telomerase activity". I couldn't find the full text, but "relatively high" in the in vitro world is pretty high, so it's probably safe to take them at their word. Both of these papers were looking at tumor cell lines which presumably have constitutively active telomerase. Inhibition in this case may or may not be relevant to normal cells.

Considering that the concentration required even for "marginal" inhibition of telomerase is essentially impossible to attain via oral dosing, I think that we can probably lay to rest the idea that resveratrol is a telomerase inhibitor. It doesn't look like it's going to be a problem in vivo.

[Louis]

None of these studies are in reference to healthy somatic cells. They're all cancer cell lines. The mechanisms are different. You're just reinforincing the point that these compounds posess strong antineoplastic properties, and likely prevent cancer. The more reason to take them with a telomerase inducer.

I obviously can't reference studies citing the telomerase inducing properties of the botanicals in product B, because their discovery is novel and as of yet unpublished.

[Louis]

Is it possible that by expressing telomerase and therefore artificially prolonging the life of a cell, that we may also be prolonging the life of senescent cells allowing them to survive longer than they should and allowing them to subsequently poison healthy cells around them causing more harm than good?

Interesting comment. Sounds like it's in regard to the recently published Mayo Clinic paper in Nature:
http://www.nature.co...ature10600.html

This paper may provide one possible explanation for why short telomere load (percentage of short telomeres) is a more accurate bio-marker for aging than mean telomere length. Percentage of short telomeres in an organ system may be a surrogate for percentage of senescent cells in the same organ system. So anything that decreases percentage of short telomeres (e.g. TA-65) may in turn decrease percentage of senescent cells. So my point is: Less overall poisoning of healthy cells in the surrounding organ system.

Anyway, that's one possible way of viewing it. That's what immediately occurred to me when I first read the paper a few days ago.

[mugener]

Lengthening of telomeres isn't by itself going to be sufficient to cure aging

But it's all about telomeres when it come to aging, isn't it?

Other then telomeres related subject, what else do we need to control in order to fully cure aging?

[Anthony_Loera]

They're all cancer cell lines. The mechanisms are different (Telomerase?). You're just reinforincing the point that these compounds posess strong antineoplastic properties, and likely prevent cancer.

It's my understanding that a cancerous cell has the telomerase function turned on permanently, while healthy somatic cells do not. However the mechanism that activates telomerase is the same and therefore telomerase inhibitors would affect healthy cells as well.

Can you find a study that says otherwise, or is this just your opinion?

A

Edited by Anthony_Loera, 07 November 2011 - 02:41 PM.

[Anthony_Loera]

Considering that the concentration required even for "marginal" inhibition of telomerase is essentially impossible to attain via oral dosing, I think that we can probably lay to rest the idea that resveratrol is a telomerase inhibitor. It doesn't look like it's going to be a problem in vivo.

I don't disagree with you entirely, but without doing the test on the full formulation of Product B with the combination of all the ingredients, we will not know for sure.
Again, we are back to waiting, which is ok.

A

Edited by Anthony_Loera, 07 November 2011 - 02:44 PM.

[GreenPower]

Interesting new thread. I've been trying to catch up on Product B and here's my take on it. Please feel three to correct me where I've got things wrong.
1. Sierra Sciences have ran low on money and therefore partnered with Isagenix in order to be able to continue to screen for better telomerase activators.
2. Bill Andrews then gave away all the results they had until now and the product developer at Isagenix then gave Bill some other drugs to test.
3. Isagenix then took most or all of the drugs which activated telomeres and mixed them with some other drugs which might (or might not) have some other beneficial effects.
4. This product in now called Product B.

I understand that Product B is not created by Sierra Sciences, but by Isagenix - using information provided by Sierra Sciences on individual drugs. But just because several of the ingredients are likely to be telomerase activators, there's no telling how your body will react on them when they are all mixed together.

Even though most of the videos hints at Product B extending your telomeres, they never actually say so. In fact, their website specifically states that that the resellers of Product B cannot:
- Claim it lengthens telomere
- Claim it induces telomerase (enzyme that can reverse telomeres shortening)
This is quite interesting, because if it doesn't claim to induce the production of telomerase, then how is is it supposed to work?

When looking at the videos we can see that Bill several times say that Product B is only one of the pillars of health and that it should be used together with the other four pillars. I think, from his expression (or lack of it) that he only says so because he was told to say so. In order for such a statement to have any relevance, they need to both have tested Product B on a group of people and measured their telomere lengths before and after, and also done so on a group which used all the five pillars of health. I understand they haven't done either of these tests.

Even if Valenzuela comes to the conclusion that Product B is a telomerase activator, I suppose this test is done "in vitro"? If so we still wouldn't know if it actually works in the human body if taken orally. I would therefore recommend Louis and everyone else taking it to measure their telomere lengths before starting to take it, and then again after half a year or a complete year. It's interesting to see different arguments to whether it works or not - but actual physical measurements are needed in order to validate the effect of the product.

[Louis]

It's my understanding that a cancerous cell has the telomerase function turned on permanently, while healthy somatic cells do not. However the mechanism that activates telomerase is the same and therefore telomerase inhibitors would affect healthy cells as well.

Can you find a study that says otherwise, or is this just your opinion?

A

>> It's my understanding that a cancerous cell has the telomerase function turned on permanently, while healthy somatic cells do not.

This is correct.

>> However the mechanism that activates telomerase is the same and therefore telomerase inhibitors would affect healthy cells as well.

This is NOT correct. The 2 mechanisms are very different.

The mechanism that activates telomerase in healthy somatic cells is well-defined and well-understood. There's a repressor protein bound to a regulator element controlling the expression of hTERT. You introduce a small molecule that attaches to the repressor protein and this dislodges it from its DNA binding site. The hTERT gene then starts expressing the protein component of telomerase which combines with plenty of available RNA component to form the telomerase enzyme.

The botanicals in product B that you keep claiming are "inhibitors" (curcumin, green tea, boswellia, resveratrol) only cause a problem in somatic cells if they somehow prevent the small molecule in question from coaxing the repressor protein off its binding site. A good screen finds the small molecules that coax the repressor protein off the DNA, and simulatneously weeds out the molecules that encourage it to hang on tighter. Since the whole process is so well-defined and well-understood, this is pretty easy to do. I trust that Bill Andrews has done it well.

In contrast, the mechanisms that activate telomerase in cancer cells are poorly-defined and poorly-understood. There's no one mechanism. Cancer cells have figured out a plethora of diiferent ways to do it, and no one is close to understanding how many ways there really are -- let alone how each individual mechanism works. For example, some cancer cells seem to replicate the telomerase gene over and over again, making many different copies. Others rely on a virus to insert itself upstream of the promoter. The list goes on and on. It varies greatly from one cancer cell line to another.

Suppose you expose some cancer cell line to some random molecule (say curcumin, green tea, boswellia, etc), and then discover via a TRAP assay that telomerase expression has been reduced. What can you then conclude about healthy somatic cells? Very little. There's a whole series of intermediate mechanisms that occur in the cancer cell in between exposure to the compound and the reduction of telomerase, which the experiment tells you nothing about -- and which, as I said, are very poorly understood to begin with. All of this has very little to do with whether or not this particular molecule (curcumin, green tea, boswellia, resveratrol, etc) will make it harder to coax the repressor protein off its binding site in a healthy somatic cell.

[Anthony_Loera]

Like I mentioned before... links to studies regarding the point you are trying to make.

In my personal opinion, your credibility has suffered greatly and I personally believe that you need to seriously climb out of that hole you dug yourself in to through your previous posts here. One way to do this is by providing peer reviewed info regarding your continuing statements if you want me to consider your words in any serious fashion.

Cheers

A

[Louis]

Oh for heaven's sake, you don't understand the science. I'll find some review articles that spell it out for you. In the mean time, just ask your CSO.

[Anthony_Loera]

All I have to do is ... look at google scholar:

Since telomerase inhibition acts by restoring the normal telomere shortening associated with cell division in normal somatic cells, tumors with a short initial telomere length would be predicted to respond most rapidly. Alternatively, therapeutic efficacy may be improved by combining telomerase inhibition with cytoreductive agents to reduce the initial tumor load. The impact of telomerase inhibition on the immune system is a potential concern since low levels of telomerase activity are found in hematopoietic cells and lymphocytes. However, given that telomere lengths in these cells do shorten in I i I v , inhibition of telomerase activity may not have a deleterious effect on normal functioning of the immune system.

As you can see their is concern for telomerase inhibition on the immune system when going after cancerous cells...
Now why would there be concerns of telomerase inhibition on non cancerous immune system cells if you stated that telomerase inhibition would only affect cancer cells?

Is it possible you can be wrong?

A

Attached Files

•  Telomerase - Exp Biol Med-1997-Chiu-99-106.pdf   1020.3KB   0 downloads

[Anthony_Loera]

Another nifty concern from attached file:

Finally, inhibitors of telomerase would potentially have effects on other human somatic cells that express telomerase, such as hematopoietic stem cells, germline cells and cells of the basal layer of the epidermis and intestinal crypts 8. We believe that these effects might be minor because stem cells of renewal tissues typically have much longer telomeres than cancer cells have and the deepest stem cells only proliferate intermittently. During the time that these cells are quiescent, telomere shortening does not occur and telomerase activity is negligible. The expected effects of telomerase inhibition on cancer cells as well as telomerase-positive normal cells are illustrated in Fig. 3. There have also been concerns that inhibiting telomerase might lead to an increase in malignancy by enhancing the genomic instability of cells. These concerns have risen from the mTR-/- knockout mice which, as compared with the mTR+/+ model, has an increased incidence of malignancies in both early and late generation cohorts 9 . There is no evidence to suggest that this would be true in humans.

I know the word potential might not be good enough, but it lends creadance that normal cells are affected. Heck see figure 3.

Attached Files

•  TelomeraseInhibitors.pdf   91.06KB   4 downloads

[Anthony_Loera]

Of course read Geron's data on normal cells activated using TAT2...

In the paper you can notice that the normal immune cells are treated with TAT2 to activate telomerase, but then are shown to be affected by a telomerase inhibitor, and also by certain pathways that... ok I will keep this part to myself... (assuming you read the paper, check all botanicals in Product B and see if any have been shown to activate or inhibit certain pathways)

Isn't that so darn cool and nifty?



TAT2
http://www.jimmunol....0/7400.full.pdf

Of course, I find it all simply interesting.

I apologize to everyone else, as we all know that it's certainly possible that this is all silly until someone tests it properly. I suppose that is my point, we simply need to wait until Product B is tested properly. All this hot air is entertaining, but that's probably all it is.


Cheers
A

Edited by Anthony_Loera, 08 November 2011 - 03:08 AM.

[niner]

Of course read Geron's data on cells activated using TAT2...
In the paper you can notice that the normal immune cells are treated with TAT2 to activate telomerae, but then are shown to be affected by a telomerase inhibitor, and also by certain pathways that some botanical ingredients appear to also act on.

Well, yeah but... Look at the telomerase inhibitor they used:

Telomerase inhibitor (TI)
The TI used in our experiments is GRN163L, a synthetic lipid-conjugated,
13-mer oligonucleotide N3' P5'-thio-phosphoramidate that is complementary
to the template region of telomerase RNA (hTR) (17). GRN163L is a
direct competitive enzyme inhibitor that binds and blocks the active site of
the enzyme (a “telomerase template antagonist”). The IC50 of GRN163L
for telomerase in human PBMCs is 1 uM (data not shown).

This is a highly potent telomerase inhibitor in an in vitro experiment. Every single piece of evidence I've seen that deals with telomerase inhibitors is in vitro and uses either a potent compound like GRN163L or uses concentrations of natural products that are so high that they aren't going to be relevant in an orally dosed product. The only point of this whole telomerase inhibitor brouhaha is to make Product B look bad, and I think Isagenix and its army of pimps is already doing a pretty good job of that. Why don't we drop the telomerase inhibitor argument and wait for the Product B test results. After all, isn't that what really matters?

Edit: I see that I've replied to an earlier version of your post, and I guess we're basically in agreement.

Edited by niner, 08 November 2011 - 03:17 AM.

[Anthony_Loera]

Yes niner, we are in agreement.
Again, I apologize. I can see that I acted silly and admit letting my feelings get me riled up on this non-issue.

A

[Louis]

The problem is that posts 134, 135, 136, are loaded with scientific inaccuracies -- and are a deliberate attempt to confuse people reading the thread. You can see that as plain as I can niner. So can anyone with any scientific training who reads through those 3 posts carefully. Then there's the personal attack in post 132, in response to a perfectly reasonable scientific argument in post 131. One of several continued personal attacks, in response to reasonable and scientifically-justified posts. I agree that there's a deliberate attempt here to make Product B look bad. This needs to stop. He is a competing product retailer, and there is an obvious conflict of interest.

[Chopperboy]

Those are pretty strong words, considering that his lab could not measure telomerase activity from Cycloastragenol... When Rita's lab at UCLA did...
A

I have a copy of the Dr Al Sears seminar video, in which Bill Andrews says he tested TA-65 and shows it on a graph alongside the HELA control. He talk lasts for about 40% of the DVD's duration.

[Anthony_Loera]

Those are pretty strong words, considering that his lab could not measure telomerase activity from Cycloastragenol... When Rita's lab at UCLA did...
A

I have a copy of the Dr Al Sears seminar video, in which Bill Andrews says he tested TA-65 and shows it on a graph alongside the HELA control. He talk lasts for about 40% of the DVD's duration.

I understand,
however he signed a confidentiality agreement about TA-65.

These again are his words from back in December:
"I also don't know what TA-65 is. In order to test it in our assays I had to sign a confidentiality agreement saying that I wouldn't try to identify it by mass spec (or other means). And, I haven't." - Bill Andrews, December 2010

RevGenetics, on the other hand, did not sign a confidentiality agreement when we decided to test TA-65 that showed that Cycloastragenol was identified in the capsule. We even stated what our testing revealed to Bill Andrews back in December. (That was actually the email I sent that prompted the partial email response I have made available above.).

Maybe we should move the "Bill Andrews" posts to another thread?
It certainly seems we will continue to receive comments about it here on this thread.

A

Edited by Anthony_Loera, 08 November 2011 - 03:44 PM.

[Anthony_Loera]

He is a competing product retailer, and there is an obvious conflict of interest.

No, as I would sell Product B if it turns out to activate telomerase. I had mentioned that before.

I don't think anyone seriously believes that supplements that induce HeLa at only a few percent will have anything but a very minor effect on aging. Especially considering that most of these compounds likely have very poor bioavailability. The important point is that this is a significant first step. Supporting and purchasing this first product provides Sierra with the crucial funding that they need to survive this economic downturn. That's why I'm such a staunch supporter and why I purchase it myself. I am trying to do my part to support this research. If you don't believe in the product, just send a check directly to Sierra. That accomplishes the same thing. - Louis

What is this quote all about Louis? How are you associated with Sierra Sciences, Isagenix and Bill?

A

Edited by Anthony_Loera, 08 November 2011 - 04:01 PM.

[Anthony_Loera]

I'll find some review articles that spell it out for you.

I like to be educated, and when I am, I acknowledge my mistakes. Please follow up on the articles you mentioned Louis.
I will limit my posts to our test results on this thread. If you want to continue to talk about Bill Andrews or theorys, lets start a new thread of discussion. Do you agree to this Louis?

I will be answering your questions and arguments in this new thread:
http://www.longecity...ierra-sciences/


Please provide me with your articles at that location, so that we don't pollute this thread anymore.

A

Edited by Anthony_Loera, 08 November 2011 - 04:07 PM.

[niner]

Guys, we need to halt the Bill Andrews discussion for a while while we get some things sorted out. Please don't post any more about Bill or his company for a while, OK? Otherwise, I'll have to close the thread. I had to queue the new thread that Anthony mentions in the previous post while we check out the appropriateness of some of the content, so it won't be visible for a while.

Edited by niner, 08 November 2011 - 07:36 PM.

[Methos000]

Hopefully Anthony will be allowed to post his assay results once they're available...

[Louis]

I'll find some review articles that spell it out for you.

I like to be educated, and when I am, I acknowledge my mistakes. Please follow up on the articles you mentioned Louis.
I will limit my posts to our test results on this thread. If you want to continue to talk about Bill Andrews or theorys, lets start a new thread of discussion. Do you agree to this Louis?

I will be answering your questions and arguments in this new thread:
http://www.longecity...ierra-sciences/


Please provide me with your articles at that location, so that we don't pollute this thread anymore.

A

>> I like to be educated, and when I am, I acknowledge my mistakes. Please follow up on the articles you mentioned Louis.

I will do so Anthony. I appreciate you saying that. I am also interested in learning as much as possible.

>> I will limit my posts to our test results on this thread. If you want to continue to talk about Bill Andrews or theorys, lets start a new thread of discussion. Do you agree to this Louis?

Yes I agree. That's very reasonable. My interest is 100% in the science. I hope we can focus any future discussions on the science, to everyone's mutual benefit.

Louis

[Louis]

He is a competing product retailer, and there is an obvious conflict of interest.

What is this quote all about Louis? How are you associated with Sierra Sciences, Isagenix and Bill?

A

I have no association whatsoever. I do not know him Bill Andrews personally, nor have I ever communicated with him ever. I have a few scientific friends from grad school and college who know him only very loosely through conferences and such; it's through them that I first heard of his work and work in telomere biology in general.

I only buy product B from Isagenix for my own personal use and for that of my family, and to support future research at Sierra Sciences. I had to register with isagenix so I could purchase it at wholesale prices. That is my only association. I do NOT sell any Isagenix products (technically, however, I sell them to myself), nor will I ever sell them. That's not meant to be a negative on the company, just a statement that I have no interest in Isagenix except to buy Product B and support the research at Sierra.

However, I will say that I am extremely happy with the results I've had with Product B. Since September, I have seen substantial improvements in the skin on the palms of my hands and feet and under my eyes. I used to have to clean hair out the drain of my shower every 2 weeks or so. I no longer need to do this, and I have seen some hair regrowth on my previously receding hairline. I've seen a minor improvement in energy, to the point that I've cut my coffee consumption down from 3-4 cups/day to 1-2 cups/day. I've also found that I'm able to operate reasonably well with less sleep.

The only possible negative side effect I've seen is what may be a very minor increase in the size of 2 moles. I am not sure, it's hard to tell. I am following this closely and with great curiosity.

[Louis]

Guys, we need to halt the Bill Andrews discussion for a while while we get some things sorted out. Please don't post any more about Bill or his company for a while, OK? Otherwise, I'll have to close the thread. I had to queue the new thread that Anthony mentions in the previous post while we check out the appropriateness of some of the content, so it won't be visible for a while.

I suggest instead calling this new thread something like "telomere biology". The focus should be on the science, and any discussions about particular companies should be in the context of the science of telomere biology ONLY. My 2 cents.

[Chopperboy]

The only possible negative side effect I've seen is what may be a very minor increase in the size of 2 moles. I am not sure, it's hard to tell. I am following this closely and with great curiosity.

I had that as well, they seemed to flare-up then shrink to smaller and flatter than they were originally. But it doesn't seem to work on very old warts which remain unchanged.

[niner]

However, I will say that I am extremely happy with the results I've had with Product B. Since September, I have seen substantial improvements in the skin on the palms of my hands and feet and under my eyes. I used to have to clean hair out the drain of my shower every 2 weeks or so. I no longer need to do this, and I have seen some hair regrowth on my previously receding hairline. I've seen a minor improvement in energy, to the point that I've cut my coffee consumption down from 3-4 cups/day to 1-2 cups/day. I've also found that I'm able to operate reasonably well with less sleep.

The only possible negative side effect I've seen is what may be a very minor increase in the size of 2 moles. I am not sure, it's hard to tell. I am following this closely and with great curiosity.

These are nice outcomes, but I wouldn't attribute them to telomere extension. With telomerase induction on the same order at cycloastragenol, I don't think that things would change this quickly. On the other hand, there are a ton of other ingredients in product b with various bioactivities; certainly looks like a CNS stimulant of some sort is on board. I hope the hair regrowth effect is real; maybe a 5-alpha reductase effect?