2189 replies to this topic

[GreenPower]

I've seen several links here to the issue of the Journal of Immunology (Nov 2008, 181: 7400-7406) where Rita B Effros et al names TAT2 as being Cycloastragenol. Here's a link to the actual content of the article: http://www.natap.org...V/060209_01.htm

Here are some interesting items from the content:
- They produced Cykloastragenol from Astragaloside IV, or more exactly "TAT2 (cycloastragenol, CAS Registry no. 84605-18-5) was prepared by purification of acid hydrolyzed Astragaloside IV".
- The study was mainly on T-Lymphocytes and only secondary on the other types of PBMC's (for example monocytes, B-cells and NK's).
- It would appear to exist an "optimal" dose of Cycloastragenol in order to give the maximum effect on telomerase activation in PMBC's from HIV-infected individuals. If the dose is too low or too high, the effect is weakening. However, they could see an effect using a very wide range of doses.
- The effect was better on cells from people with shorter telomeres to start with (HIV and AIDS patients).
- They say that "telomerase activation, typically peaks 24–48 h after TAT2 treatment". I would therefore personally be careful with using any kind of telomerase inhibitor during this time period.
- There was no no evidence of "immortalization", or as they state it "in all ex vivo studies conducted to date, there was no evidence that TAT2 promoted loss of growth control or transformation". Which is to say no cells turned cancerous.
- They also say that "we have observed that the telomerase up-regulation effects are short term and reversible; removal of TAT2 from cells returns telomerase levels to baseline within a few days without any effects on cell viability". Which is to say that after treatment the cells goes back to express as much telomerase as they did before.

Because I find these kind of reports somewhat hard to decipher, I would appreciate if someone with better skills in cellular biology/bio chemistry could try to pry more useful information from this report - and also correct me if my conclusions above are inaccurate.

[TheFountain]

This thread
I'm sure that all of us would love to see such studies. However, to my knowledge, no supplemental intervention has ever convincingly demonstrated an extension in maximum lifespan in normal, healthy members of a mammalian species.

That is because awareness of such potential intervention has not occurred till this generation. Thus there is no 'but' only uncertainty in the face of experimentation. But I think my generation has its foot in the door much deeper than any previous generation. To think otherwise is just ignoring the facts...

Edited by TheFountain, 18 October 2009 - 10:24 AM.

[unglued]

This thread
I'm sure that all of us would love to see such studies. However, to my knowledge, no supplemental intervention has ever convincingly demonstrated an extension in maximum lifespan in normal, healthy members of a mammalian species.

That is because awareness of such potential intervention has not occurred till this generation. Thus there is no 'but' only uncertainty in the face of experimentation. But I think my generation has its foot in the door much deeper than any previous generation. To think otherwise is just ignoring the facts...

Actually, researchers have been studying supplements for generations. Mouse generations, not human. It takes a lifetime of study (a murine lifetime, not human) to prove that something extended maximum lifespan, by definition. And there have been some positive studies for resveratrol, which is why AgeVivo added those qualifiers: The 2006 study in mice that were well above a healthy weight, and the later one in healthy mice that didn't convincingly demonstrate an increase in maximum lifespan. Astral Fruit, on the other hand -- or the chemical it's purportedly identical to -- has not yet been tested in animals of any kind, as far as I've heard, only in human cells white blood cells in vitro.

But I have the impression that there used to be a consensus that maximum life extension in mammals was impossible, and currently that's being seriously challenged. If it turns out to be possible, everyone currently alive has a chance, but not a guarantee, that people never had in previous centuries. And obviously, the younger one is, the better one's chances. Exactly the same way that my generation was the first one to have a chance of living in space.

[sasha59]

Hey, a couple things regarding what "GreenPower" said:

- They produced Cykloastragenol from Astragaloside IV, or more exactly "TAT2 (cycloastragenol, CAS Registry no. 84605-18-5) was prepared by purification of acid hydrolyzed Astragaloside IV".

Originaly Astragaloside IV was being used as an equivalent to TA-65 when cytoastragenol was not available and it wasn't certain that it was the substance TA sciences uses. Now however it seems decided that TA sciences does in fact use cytoastragenol, and moreover, before anyone was competing with them they felt that going the extra step was necessary. Does this make anyone besides myself concerned?

- They say that "telomerase activation, typically peaks 24–48 h after TAT2 treatment". I would therefore personally be careful with using any kind of telomerase inhibitor during this time period.
also correct me if my conclusions above are inaccurate.

I had previously understood that a three hour gap was an adequate time separation between taking Astragaloside and something else (curcumin for instance). What is stated above suggests that this is not the case. I'm concerned that I'm more or less canceling every thing I'm taking out which obviously would be a waste. I checked the TA sciences web site regarding their TA-65 support Pak ingredients, but the page that used to describe the ingredients is now missing.

The postings to this thread ground to a halt after two people who had indicated that they would be posting the results of their telemere measurments didn't do so. I checked the Revgenetics site and found that Anthony has taken down his telemere report as well.

I'm left with the (sincere) question: Is there a reason for me to be taking this stuff any more? I get the feeling that the faith has been lost.

Sasha

Edited by sasha59, 03 November 2009 - 08:51 PM.

[Anthony_Loera]

Sasha,

you said I took down my telomere results?

Hmm...
no, I still see the link on the first one on the website:
August 2008 Tests

The second one found in this thread still works as well:
March 2009 Tests

My new results are not in yet for a few reasons:
1- I was waiting for another company to reply to my questions (This didn't happen, no answers were given even though I was promised answers)
2- I got a little side tracked on another project, that is important for me and possibly a few other people. (basically a new Mastergene® product for P16)
3- A personal reason that pushed back multiple work projects.

I promise to put my new blood tests in as soon as I can.
Sorry for the delay on the Astragaloside IV related telomere tests.

Cheers
A

Edited by Anthony_Loera, 03 November 2009 - 09:24 PM.

[GreenPower]

The postings to this thread ground to a halt after two people who had indicated that they would be posting the results of their telemere measurments didn't do so. I checked the Revgenetics site and found that Anthony has taken down his telemere report as well.

I'm left with the (sincere) question: Is there a reason for me to be taking this stuff any more? I get the feeling that the faith has been lost.

Sasha

There are two reasons I've not been posting the results from my "detailed procedure" from the Canadian lab.
1. I haven't had the time.
2. I had to confirm the results of the standard deviations which I found, and still find, somewhat strange.

The short of it is that Astragaloside IV did not extend my telomeres. Instead I experienced a loss in telomere lengths in Granulocytes and Memory T-cells which are statistically significant - and larger than they should be. The other changes were not statistically significant, but had lower numbers than in the first test.

After thinking hard about it, I think the most logical explanation of this behavior is that
1. All types of telomeres in the first test (with one clear exception) were longer than they should have been for my age, even though I've been working under "great stress" for many years.
2. I've continued to work under great stress during the whole period, and still do.
3. Before I took my "baseline test" I used a completely other sort of standardized Astragalus supplement (see earlier posts), which might have been working rather well to counteract the harmful effects of stress on many types of cells (excluding NK-cells). They might actually have been extending telomere in some types of cells (a wild guess, and I have no numbers to support that statement)

Three other explanations are of course
1. One of the tests was executed in the wrong way and returned the wrong results.
2. Astragaloside IV actually decrease the lengths in telomeres in some types of cells.
3. The lab mixed up one of my tests with someone elses. I think this is unlikely, though. My short telomeres in NK-cells are quite visible in both tests - and acts like a kind of identifier, saying both of the test results probably belong to me.

So now I'm now trying out Cycloastragenol instead. If that doesn't work I will probably switch back to my old standardized Astragalus extract.

A very interesting effect of my last test period, though (using Astragaloside IV and two other compounds mentioned in earlier posts) is that all of a sudden all my (measured) telomeres seem to have been kind of synchronizing themselves in length.
In order, the test measures the following:
- Lymphocytes
- Granulocytes
- CD45RA+/CD20-(Naïve T)
- CD45RAneg (Memory T)
- CD20-pos (B Cells)
- CD57-pos (NK Cells, or rather, I think this is a subset of NK Cells)

In the first test, which I did about half a year ago, the SD's were ±0.6, ±1.2, ±0.4, ±0.7, ±0.7 and ±0.7, which looks kind of normal. In the last test, however, the SD's were ±0.0, ±0.0, ±0.0, ±0.0, ±0.0 and ±0.0 (!). I therefore asked the lab if they had measured a population of telomeres large enough to make the results statistically significant. The answer to that (leaving out the details of the answer), would seem to "yes".

Anyone else been observing the same behavior?

[Anthony_Loera]

Hi Guys,

I didn't notice this was being referenced in google scholar until recently:
http://www.jimmunol....Abstracts/90.30

It is important to us, as we are involved in providing more cycloastragenol and resveratrol for these types of items and studies.

Cheers
A

[edward]

Interesting how all the cells measured are immune specific cells:

- Lymphocytes
- Granulocytes
- CD45RA+/CD20-(Naïve T)
- CD45RAneg (Memory T)
- CD20-pos (B Cells)
- CD57-pos (NK Cells, or rather, I think this is a subset of NK Cells)

and it is the concentrated astragalus extracts that have been used since the advent of Chinese trad medicine for boosting the immune system

[GreenPower]

Interesting how all the cells measured are immune specific cells:

- Lymphocytes
- Granulocytes
- CD45RA+/CD20-(Naïve T)
- CD45RAneg (Memory T)
- CD20-pos (B Cells)
- CD57-pos (NK Cells, or rather, I think this is a subset of NK Cells)

and it is the concentrated astragalus extracts that have been used since the advent of Chinese trad medicine for boosting the immune system

Yes, but it's not really "concentrated Astragalus" I've been taking. It's more like "concentrated Astragaloside IV", which is only one substance out of quite many in the Astragalus plant. This link might give a perspective on how many others there are: http://sun.ars-grin.....xsql?taxon=140 .

This evening I've got some time over, so I will "depersonalize" and shrink (in size) both my test results from the Canadian lab and post them here.

[GreenPower]

This evening I've got some time over, so I will "depersonalize" and shrink (in size) both my test results from the Canadian lab and post them here.

Here are my test results from the Canadian lab.

File 1: TLM_2009_March_Personal_Info_Removed.jpg
This is as close as I came to a "Baseline test". However, there are a couple of issues to be noted.
1. When the test was taken I'd been working in a very stressful environment for many years. There's a connection between stress and short telomeres in the immune systems. This connection is rather well described in this presentation: by Elisabeth Blackburn, this years winner of the Nobel prize. This might (or might not) be the reason for my short telomeres in NK-cells.
2. Before this Baseline test I took standardised Astragalus Root Extract for more than half a year (0.5% glucosides, 70% polysaccharides) 225 mg, Raw Astragalus Root Powder 250 mg). First once a day, but soon three times a day (morning, lunch, evening). I also took Ginkgo biloba L. 100 mg (24 mg ginkgoflavonidglycosides , 6 mg terpenoids) twice daily.
3. Then, also before the Baseline test, I also had a period of about quarter when I took an ordinary root powder version of Astragalus (470mg, not standardized).
4. In two Cortisol tests I did before before the above mentioned baseline test, I had "really bad" and "very poor" (as in low levels) results respectively. Cortisol is a "stress hormone", and the levels I had in the first test were way to close to the kind you usually associate with people suffering from Addison's Disease: http://en.wikipedia....dison's_disease . The other test (after six months on standardized Astragalus extract + Gingko Biloba) was somewhat better but still not good.

The point I want to make is that I did not start out my test period as an ordinary person. All of the items above have probably had one effect or another on my telomere lengths before I took my baseline test.

File 2: TLM_2009_September_Personal_Info_Removed
This is the follow-up test I did about half a year after the first test. The time since the first test was divided into three parts.
Period 1: Three months on Astragaloside IV (3 x 33mg) which was spread out during the day (morning, lunch, evening).
Period 2: Rest period for two weeks. No supplements were taken.
Period 3: Three months on Astragaloside IV 100mg dose with Chitosan (1 x 100mg) taken in the morning.
The latter period also included the use of Orlistat (3x120mg) with each meal and Gingko Biloba (1x100mg) in the evening.

The weekend before the follow-up test I did not take any supplements at all.

Note that I also took some vaccinations and prophylaxis in relation with a vacation during period 3.
- Epaxal (Hepatite A)
- Dukoral (Cholera)
- diTeBooster (Tetanus)
- Lariam/Mefloquine (Malaria)
These might or might not have had an effect on the immune system.

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Edited by GreenPower, 06 November 2009 - 07:05 PM.

[unglued]

This evening I've got some time over, so I will "depersonalize" and shrink (in size) both my test results from the Canadian lab and post them here.

Thanks to GreenPower for sharing his before-and-after results on A4. A sample size of two (along with Anthony's results from 14 and 8 months ago) is a lot better than one, although it's still not enough to tell us much.

So far, I'm beginning to find it a little disturbing that both subjects who posted results have had marked decreases in telomere length in a short time, instead of the increase we would have hoped to see. Looks like the equivalent of years of shortening in six months. With all the other variables affecting each subject's health, I don't know how significant that is (and remember that the SD is from comparing each blood draw against itself), but the only other evidence we have to weigh this against is in vitro studies of a molecule that Anthony thinks from the patent description was identical to Astragaloside IV or the related molecule Cykloastragenol, right?

[Anthony_Loera]

Hi Unglued,

A4 was our first product and the small 33mg dose did not show an increase in telomere length as shown in my two first tests, but with the error rate between blood draws could show that not much did change as well.

So far, I am not sure if increasing my dose to 100mg has made a difference, but my tests haven't come back. I am hoping for a number greater than the error rate between blood draws otherwise... it will not show a definite result either way.

After the latest tests come back, I will be testing Cycloastragenol. I know that in-vitro cycloastragenol seems to do it's within a week, which is quite amazing according to some folks. so We shall see if it does anything at 5mg, as my first test.

Cheers
A

Edited by Anthony_Loera, 06 November 2009 - 10:49 PM.

[saxiephon]

Hi Unglued,

A4 was our first product and the small 33mg dose did not show an increase in telomere length as shown in my two first tests, but with the error rate between blood draws could show that not much did change as well.

So far, I am not sure if increasing my dose to 100mg has made a difference, but my tests haven't come back. I am hoping for a number greater than the error rate between blood draws otherwise... it will not show a definite result either way.

After the latest tests come back, I will be testing Cycloastragenol. I know that in-vitro cycloastragenol seems to do it's within a week, which is quite amazing according to some folks. so We shall see if it does anything at 5mg, as my first test.

Cheers
A

Anthony,

When I viewed a TA Science video recently there was a comment that the dosage was increased to 100 mg which gave much more impressive results. Was this Cycloastragenol or something else? If they were discussing Cycloastragenol, 5 mg per day may be insufficient to effectively activate telomerase.

SAX

Edited by saxiephon, 07 November 2009 - 08:43 PM.

[Anthony_Loera]

Hi SAX.

I think I answered that here:
http://www.imminst.o...o...st&p=351581

Cheers
A

[bdelfin]

One important indicator for the importance of telomeres is out in this week's Proceedings of the National Academy of Sciences.

Basic summary here:
Money quote: "More specifically, the researchers found that participants who have lived to a very old age have inherited mutant genes that make their telomerase-making system extra active and able to maintain telomere length more effectively. For the most part, these people were spared age-related diseases such as cardiovascular disease and diabetes, which cause most deaths among elderly people."

Abstract:
Telomere length in humans is emerging as a biomarker of aging because its shortening is associated with aging-related diseases and early mortality. However, genetic mechanisms responsible for these associations are not known. Here, in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls, we studied the inheritance and maintenance of telomere length and variations in two major genes associated with telomerase enzyme activity, hTERT and hTERC. We demonstrated that centenarians and their offspring maintain longer telomeres compared with controls with advancing age and that longer telomeres are associated with protection from age-related diseases, better cognitive function, and lipid profiles of healthy aging. Sequence analysis of hTERT and hTERC showed overrepresentation of synonymous and intronic mutations among centenarians relative to controls. Moreover, we identified a common hTERT haplotype that is associated with both exceptional longevity and longer telomere length. Thus, variations in human telomerase gene that are associated with better maintenance of telomere length may confer healthy aging and exceptional longevity in humans.

Full paper (subscription required -- anyone have access?)

[Harold_f]

"[...] Then someone else discovers that Japanese knotweed, which is much easier to grow than grapes, contains much more of the molecule. I wonder if anyone is searching for such a plant, using techniques similar to those that Geron used to discovered the molecule in the first place, by looking for TA-activating molecules in astragalus."

Because of the nature of the molecules, only a closely related species seems plausible as an alternative source: The astragalosides are far more complex molecules than resveratrol, and hence very unlikely to be evolved repeatedly in separate lineages, and likewise seem unlikely to be retained without modification over long evolutionary times.

Molecular complexity also makes production by genetically engineered bacteria unlikely, for now, since the required level of metabolic engineering is beyond the state of the art.

Resveratrol vs. Astragaloside IV:

[Anthony_Loera]

Thanks Harold for this (as well as your older post on curcumin and pH)

It seems from your knowledgeable answer that only Astragalus related species may continued to be studied in the near future, for more molecules that activate telomerase.

Cheers
A

[Anthony_Loera]

Sasha,

you said I took down my telomere results?

Hmm...
no, I still see the link on the first one on the website:
August 2008 Tests

The second one found in this thread still works as well:
March 2009 Tests

My new results are not in yet for a few reasons:
1- I was waiting for another company to reply to my questions (This didn't happen, no answers were given even though I was promised answers)
2- I got a little side tracked on another project, that is important for me and possibly a few other people. (basically a new Mastergene® product for P16)
3- A personal reason that pushed back multiple work projects.

I promise to put my new blood tests in as soon as I can.
Sorry for the delay on the Astragaloside IV related telomere tests.

Cheers
A

Here is my latest Telomere tests:
November 2009 Tests

I haven't checked this one yet.
I just got it a few minutes ago, and will probably look at it later after I work on my daughters crib.
(She tried to lift herself out of it today... scared the heck out of me.)

Cheers
A

Edited by Anthony_Loera, 17 November 2009 - 12:36 AM.

[Anthony_Loera]

Ok...

See the little chart below for the results using Astragaloside 4:
Even with the error rate of 0.5kb between blood draws, it appears the Granulocytes didn't react and shows shortening outside of the error rate, while the Lymphocytes still fall within the error rate.

I will check if Cycloastragenol is better on my personal telomeres. I will use it for the next 6 months, then do another test.
I have added the other cell types as well as an additional metric for my next tests: Naïve T, Memory T, B Cells and NK Cells


Cheers
A

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Edited by Anthony_Loera, 17 November 2009 - 01:15 AM.

[rwac]

This problem of telomerase activation actually shortening telomeres has been bothering me a bit.

Here's a possibility. The telomerase is keeping the cell population alive for longer, which means that the telomere
lengths will get shorter over time, due to cells aging in other ways and getting less efficient.

So you're actually saving stem cell capacity by keeping cells alive longer.

It's an interesting hypothesis.
If it's true, you should see the telomeres suddenly become longer when the current cell population starts to die.

[GreenPower]

Ok...

See the little chart below for the results using Astragaloside 4:
Even with the error rate of 0.5kb between blood draws, it appears the Granulocytes didn't react and shows shortening outside of the error rate, while the Lymphocytes still fall within the error rate.

I will check if Cycloastragenol is better on my personal telomeres. I will use it for the next 6 months, then do another test.
I have added the other cell types as well as an additional metric for my next tests: Naïve T, Memory T, B Cells and NK Cells


Cheers
A

Would it be possible for you to ask the Canadian lab what your standard deviations (SD) were in your last test? I'm curious to see whether you they were all zero or not.

[Logan]

I have a question for everyone about taking astragalus and resveratrol. What do we know about taking resveratrol and astragalus in the same day? Does anyone educated on the subject believe it is fine to take these two on the same day as long as they are taken far enough apart from eachother? For example, take resveratrol in the morning and astragalus in the evening or at night.

[TheFountain]

I bought some now food brand astragalus which kind of smells like peanut butter to me. Is this odd?

[Anthony_Loera]

Hi Greenpower,

I just emailed them that question. I didn't notice that the SD was not included in those last results.

[mrak1979]

Thanks for posting interesting test results, but my question is why would a4 shorten telomeres? I can understand ir it does nothing or lengthens it.

[Anthony_Loera]

There is an error rate of 0.5kb on each blood draw, mrak1979. And... telomeres do shorten over time naturally.

I think taking both of these into account, doesn't show much in the tests using A4.

A

[mrak1979]

ic, I think that was mentioned before in another post. thanks for the reminder. I really hope Cycloastragenol shows better results.

Edited by mrak1979, 18 November 2009 - 11:15 PM.

[TheFountain]

Does anyone know why Astragalus might smell like peanut butter?

[Anthony_Loera]

Does anyone know why Astragalus might smell like peanut butter?

Sorry, that one is new to me. I don't think it should smell like peanut butter. How many grams are you taking a day, 20 grams or more?
A

[TheFountain]

Does anyone know why Astragalus might smell like peanut butter?

Sorry, that one is new to me. I don't think it should smell like peanut butter. How many grams are you taking a day, 20 grams or more?
A

Well I recently used up a bunch of astragalus I ordered a few months ago from swanson. I had some lying around from last months iherb shipment. I have not taken it yet. The exact product is this and up till I ran out I was taking about 2-3 grams a day. I would say this stuff smells more like peanut butter cookies rather than actual peanut butter.