2189 replies to this topic

[unglued]

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.

The whole idea of A4 was the following guess, right?

Here's another quote from sci.life-extension, user jc101.

here are the use patents for Astragalus and telomerase:
http://tinyurl.com/2yypov
http://tinyurl.com/3db889

Telomerase induction tested originally using a 10:1 95% ethanolic
extract of Astralagus root (this extract was called GRN925)

The most potent compound in the extract seems to be astragaloside IV
or cycloastragenol, one of which which may be the GRN-665 (TA-65)
TAT0002 molecule. ...

But now the thinking is that Cycloastragenol is TA-65. Which means that A4 isn't TA-65, right?

So for all we know, A4 is TA-65's evil cousin that shortens telomeres (or at best, inhibits telomerase, a little bit like Geron's cancer drug candidate, imetelstat, but not so well characterized).

We can't really know for sure, with just one or two subjects. Maybe they were both fighting off an infection or something. I guess we'll never know more about A4 since Anthony is switching to Cycloastragenol. There sure doesn't seem to be any evidence to support our hopes that A4 is an anti-aging supplement.

[Anthony_Loera]

A4 is TA-65's evil cousin that shortens telomeres

Why do you say that? If you include the error rate between blood draws and natural shortening of telomeres, do you still consider for that to be true? It's hard to know what is actually happening at this time.


Now, if I personally get better results from Cycloastragenol... great!
I will then need to have everyone I know switch over.

A

Edited by Anthony_Loera, 20 November 2009 - 01:11 PM.

[unglued]

Why do you say that? If you include the error rate between blood draws and natural shortening of telomeres, do you still consider for that to be true? It's hard to know what is actually happening at this time.

I said "for all we know". What I mean by that is that your results are just as consistent with A4 making telomeres suddenly get shorter as with making them longer. It's also likely it does nothing at all. The only theoretical reason to expect it to lengthen telomeres was the assumption that it was the same molecule as TA-65, and we have some idea from in vitro studies of what TA-65 does. But if Cycloastragenol is TA-65, then A4 is not TA-65, right? So what do we really know about A4, except that it's a component of a plant that is traditionally believed to have good effects?

[GreenPower]

We can't really know for sure, with just one or two subjects. Maybe they were both fighting off an infection or something. I guess we'll never know more about A4 since Anthony is switching to Cycloastragenol. There sure doesn't seem to be any evidence to support our hopes that A4 is an anti-aging supplement.

Actually, I forgot that I had a rather severe diarrhea during the vacation I had in my second period on AIV. This was about two months before the second telomere test. It was caused by a "Caesar Salad" which had been washed in water from an ordinary Thai water tap.

I used Loperamid and recovered in about two days. However, the bacteria/virus/parasite that was the cause probably didn't have a positive effect on my immune system.

[Anthony_Loera]

No one knows what TA-65 is.
I think it may likely be A4 and not Cycloastragenol at this time.

[mrak1979]

I think it may likely be A4 and not Cycloastragenol at this time.

Anthony, can you give us your scientific reasons for the above statement?

[bsm]

What units are his telomere lengths are meassured in? I see a measurement of 9.1 something. What is 9.1? What lab did he use to measure telomere lengths? I thought TA-Sciences uses the same canadian lab Anthony does. If so, their measurements are not sensesitive enough to measure a years difference in length anyway.

Also, those pictures of the doctor look like an advertisement. I do not trust anything that looks so much like a billboard advertisement.

Edited by bsm, 28 November 2009 - 04:40 AM.

[Anthony_Loera]

I think it may likely be A4 and not Cycloastragenol at this time.

Anthony, can you give us your scientific reasons for the above statement?

mrak1979,

Folks initially believed that it was initially cycloastragenol, because it originally came in 5mg capsules. No one suspected that it could have been Astragaloside IV for that simple reason. Now, the latest report is that many in the TA Sciences camp are increasing their dosage by 20 fold, to 100mg. That leads me to believe that they were simply using Astragaloside IV all along and were maximizing profit while being cautious. Until you (or anyone else for that manner) can provide me capsules to test in a lab, then (as they say...) we have to follow the money.

It is most beneficial for a supplement company to stop from stating things on a label, to limit competition that can easily copy them. I was in fact talking to a lawyer regarding the labeling of the TA Sciences product, and was told that they would not be able to sell it in it's present manner with the general public. The label does not appear to meet FDA requirements, and may need to state the ingredients in the formulation. Even a proprietary formulation requires the ingredients to be shown on the label, even if the exact amounts are not known.

I believe they are using Astragaloside IV, because of the recent increase in dosage that was reported. You have to realize that for years they were reporting only 5mg was necessary. Then to have the company jump to 20 times that amount, seems very dramatic and suspicious. It leads me to believe they were using Astragaloside IV all along.

mrak1979 can you provide your scientific reasons for believing it is not Astragaloside IV (or Astrgenol) but in fact Cycloastragenol?
Again, send me some capsules and I will have them tested and remove all doubt.

Cheers

A

Edited by Anthony_Loera, 28 November 2009 - 04:15 PM.

[mrak1979]

I think it may likely be A4 and not Cycloastragenol at this time.

Anthony, can you give us your scientific reasons for the above statement?

mrak1979,

Folks initially believed that it was initially cycloastragenol, because it originally came in 5mg capsules. No one suspected that it could have been Astragaloside IV for that simple reason. Now, the latest report is that many in the TA Sciences camp are increasing their dosage by 20 fold, to 100mg. That leads me to believe that they were simply using Astragaloside IV all along and were maximizing profit while being cautious. Until you (or anyone else for that manner) can provide me capsules to test in a lab, then (as they say...) we have to follow the money.

It is most beneficial for a supplement company to stop from stating things on a label, to limit competition that can easily copy them. I was in fact talking to a lawyer regarding the labeling of the TA Sciences product, and was told that they would not be able to sell it in it's present manner with the general public. The label does not appear to meet FDA requirements, and may need to state the ingredients in the formulation. Even a proprietary formulation requires the ingredients to be shown on the label, even if the exact amounts are not known.

I believe they are using Astragaloside IV, because of the recent increase in dosage that was reported. You have to realize that for years they were reporting only 5mg was necessary. Then to have the company jump to 20 times that amount, seems very dramatic and suspicious. It leads me to believe they were using Astragaloside IV all along.

mrak1979 can you provide your scientific reasons for believing it is not Astragaloside IV (or Astrgenol) but in fact Cycloastragenol?
Again, send me some capsules and I will have them tested and remove all doubt.

Cheers

A

Thanks for the detailed reply, Anthony. I understand your reasoning now, but could it have been cycloastragenol that they upped the dosage to 100mg? Or is that too potent a dose for cycloastragenol that it doesn't seem possible?

[Anthony_Loera]

From my understanding, the dose does seem a bit too high for my comfort level.

The price is also extremely high as it doesn't leave them (TA Sciences) too much profit at all on a yearly basis. I have compared the wholesale price per mg of cycloastragenol to their yearly retail price for their Patton protocol, and it doesn't make sense from a profit standpoint, if they are in fact using Cycloastragenol as they would probably be losing quite a bit of money. We sell Cycloastrgenol for $69.98 for a 30 day supply. Now if TA Sciences had low margins similar to our products, then we can calculate that 20x that amount would come out to $1399 a month... then you can calculate the yearly amount of $16,795 just for the supplement regardless of any tests or licensing... and it simply doesn't make sense if they are using Cycloastragenol.

Of course I could be wrong, however I find that unlikely.
That is why I don't mind having the capsules tested to remove any doubt.

Cheers
A

[xtol]

From my understanding, the dose does seem a bit too high for my comfort level.

The price is also extremely high as it doesn't leave them (TA Sciences) too much profit at all on a yearly basis. I have compared the wholesale price per mg of cycloastragenol to their yearly retail price for their Patton protocol, and it doesn't make sense from a profit standpoint, if they are in fact using Cycloastragenol as they would probably be losing quite a bit of money. We sell Cycloastrgenol for $69.98 for a 30 day supply. Now if TA Sciences had low margins similar to our products, then we can calculate that 20x that amount would come out to $1399 a month... then you can calculate the yearly amount of $16,795 just for the supplement regardless of any tests or licensing... and it simply doesn't make sense if they are using Cycloastragenol.

Of course I could be wrong, however I find that unlikely.
That is why I don't mind having the capsules tested to remove any doubt.

Cheers
A

The conclusion that TA-65 is A4 and not Cycloastragenol seems to completely turn on the veracity of Anthony's source of information about TA-65 dosing changes. If Anthony's source is providing absolutely known-to-be-true information, then it would seem TA Sciences is using A4, and if they have been using A4 all along, even at 5mg doses, then we have reason to regard all TA Sciences claims (and the company itself) as suspect - especially given the results of Anthony's tests. I have not reached a firm conclusion yet, but am coming around to the idea that there are no limits to scamming for profit, even under the (direct or indirect) auspices of a supposedly respectable firm as Geron.

[stephen_b]

if they have been using A4 all along, even at 5mg doses, then we have reason to regard all TA Sciences claims (and the company itself) as suspect - especially given the results of Anthony's tests.

Another possibility is that they were just being conservative in the beginning.

[numbered]

Or maybe they somehow have produced quantities of Cycloastragenol in a cost effective way and they are actually dosing 100mg of it. There is no way to be certain unless ta65 is tested

[Anthony_Loera]

There is no way to be certain unless ta65 is tested

I agree Nikolis.

Anyone have a few of these capsules? I promise I won't say how I got them.
If you want to be completely anonymous, simply send them to my office:

RG - Attn: Anthony
12460 SW 8 ST
STE 200
Miami FL 33184

Cheers
A

Edited by Anthony_Loera, 30 November 2009 - 07:15 PM.

[Budiutomo]

Hi Edward or any ImmInst Org member on this thread,

Has anyone try the Vitacost Astragalus extract

http://www.vitacost....ng-120-Capsules


Supplement Facts
Serving Size: 2 Capsules
Servings per Container: 60
Amount Per Serving % Daily Value
Astragalus Extract (Astragalus membranaceus) (standardized to 0.5% hydroxy-3-methoxy-isoflavone-7)(root) 1000 mg *
*Daily value not established.
Other Ingredients: Kosher gelatin (capsule), ric

They charge only $15.00 for 60 serving . On a 1000mg a day, it can last my parent 2 months worth of membranaceus supply. This is the lowest supplement for astragalus that I have find so far. But, I'm nervous to buy it because I think it does not have much high level of Astragaloside IV in it.



Anybody that has taken this product, please also commend on this or maybe recommend an affordable source for Astragaloside IV.

[Anthony_Loera]

You will need to take 20 grams a day, to equal the amount of A4 that some of us provide in one capsule.

Cheers
A

[xtol]

This seems to be the latest Patton Protocol:

First 6-Month TA-65 Dosing Instructions
You have received 3 bottles of TA-65 consisting of 25mg capsules (180 capsules per bottle) for the 1st 6 months. Your recommended dose is 50mg/day (2 capsules daily). After you finish the 1st bottle, increase your dosage to 100mg/day (4 capsules daily).

1. How to take TA-65 daily:
We recommend taking TA-65 capsules on an empty stomach. You may take TA-65 either in the morning or in the evening before bedtime. If you take TA-65 in the morning, it should be taken before breakfast. Please wait approximately 1 hour after taking TA-65 before eating or taking any other nutritional supplements.
Please note: If you take resveratrol, curcumin (tumeric), quercetin, green tea extract, or silymarin (milk thistle); you should take those products approximately 12 hours before or 12 hours after taking TA-65. These supplements should not be taken at the same time as TA-65.

2. Phase into the desired dosage:
Start by taking one 25mg capsule per day for 8 days on an empty stomach.
After 8 days take two capsules together at the same time so that you are doubling the dose up to 50 mg/day. Continue taking 2 capsules daily until you finish the bottle.

After you finish the first bottle, we suggest that you take a two-week break。
After the two-week break, increase your dosage to 100mg/day by taking 4
capsules together at the same time. Continue taking 4 capsules until the remaining two bottles are both finished.

We do not expect that you will experience any side effects with any of these doses, but if you have any concerns, please contact T.A. Sciences or your doctor.

Copied from:
http://docs.google.c...s-pd0GACM2IPIbQ

If TA-65 is A4 then how can the seemingly dramatic improvements reported by TA Sciences in 2005 be true, given the reported dosage of 5mg, and given Anthony's labs using 100mg? Something just doesn't seem right.

The testimonials on the TA Sciences website report dramatic improvements in biomarkers, e.g., hundreds of additional base pairs. Have these occurred using 5mg or 100mg?

I have been taking 100mg A4 for at least 6 months and have noticed none of the reported improvements. For the past month I have added 2.5mg Cycloastraganol sublingually along with A4.

Does anyone know of other possible extracts from astragalus besides A4 and Cycloastraganol that COULD be the real TA-65?

[Anthony_Loera]

The testimonials on the TA Sciences website report dramatic improvements in biomarkers, e.g., hundreds of additional base pairs. Have these occurred using 5mg or 100mg?

As far as I know, 5mg.

They could be using Astragenol or another substance (see the beginning of this thread for a list)

Cheers
A

[niner]

If TA-65 is A4 then how can the seemingly dramatic improvements reported by TA Sciences in 2005 be true, given the reported dosage of 5mg, and given Anthony's labs using 100mg? Something just doesn't seem right.

The testimonials on the TA Sciences website report dramatic improvements in biomarkers, e.g., hundreds of additional base pairs. Have these occurred using 5mg or 100mg?

Along with TA-65, didn't the Patton Protocol also include a raft of other supplements? Maybe the improvements in biomarkers were from something else? Or some interaction between the supplements and the TA-65? Or maybe they were making everything up? Or maybe they have some kind of tweaked formulation, or outright different molecule, compared to what we have access to? Their increase in dosage by a factor of 20 doesn't seem quite right given the results they reported at the lower dose.

[kitinje]

I had a look at almost all telomerase related resarches that were published in the last month.


1) Telomerase shortening is not only related to cell scenescene but the progessive shortening itself has an effect on the epigenetic expression of certain genes.

Interestingly, epigenetic alterations at heterochromatic regions [telomeres] are proposed to lead to changes in gene expression associated with aging (14–16).[..]
An important question to determine ishowthe various types of DNA damage impact gene expression changes associated with organismal aging. [..]
In this study, we focused on the isolated effect of dysfunctional telomeres on global genome regulation. Using a mouse model system, we provide evidence that progressive telomere shortening in stratified epithelia, such as the skin, is linked to global deregulation of the mammalian transcriptome and loss of maintenance of epigenetic silencing mechanisms.

Nature Reviews. Genetics, DECEMBER 2009 VOL 10 NO 12
original article:
Schoeftner, S. et al. Telomere shortening relaxes X chromosome inactivation and forces global transcriptome alterations. Proc. Natl Acad. Sci. USA 3 Nov 2009

2) Short Telomeres are Sufficient to Cause the Degenerative Defects Associated with Aging
Am J Hum Genet. 2009 Nov 25

3) Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall.
Circulation. 2009 Nov 30

Exercise upregulated telomerase activity in the thoracic aorta and in circulating mononuclear cells compared with sedentary controls, increased vascular expression of telomere repeat-binding factor 2 and Ku70, and reduced the expression of vascular apoptosis regulators such as cell-cycle-checkpoint kinase 2, p16, and p53. [..]
Conclusions-Physical activity regulates telomere-stabilizing proteins in mice and in humans and thereby protects from stress-induced vascular apoptosis.

this is nothing new in fact, as it is also known that physical exercise can reduce cancer risk:

American Cancer Society, August 2004

The 2005 edition of annual IHRSA Report on health benefits of exercise cites no less than ten tumours for which physical activity is shown to effectively prevent the risk of illness

Which means that telomerase upregulation due to exercise activity in fact does not give athletes a better chance of getting cancer.

The study, "Genetic Variation in Human Telomerase is Associated with Telomere Length in Ashkenazi Centenarians," which appears in the November 9 online issue of the Proceedings of the National Academy of Sciences,
shows how their ability to preserve telomeres length is related to their very long and healthy lifespan, and not to an increased cancer risk.

Edited by kitinje, 06 December 2009 - 07:12 PM.

[kitinje]

Anyway it appears to me that telomere lengthening through the use of telomerase upregulating compounds such as ta-65/cycloastragenol could potentially be safer at a young age than in a very old one in a logic of "the younger, the better" due to mutations and dna damage that could more likely be present at an old biological state.
Ashkenazi Centenarians better maintenance of their telomeres is a lifetime long process that did not start at old age.
But this is just my opinion.


Anthony, have you switched to Cycloastragenol?
It would be nice to see your results in a few months, since nobody here has managed to really enlengthen telomeres by now,
is someone in this forum taking real TA-65?

Just to realize if their compound does really what stated on their website

“My telomeres got longer by 100 base pairs at 3 months and an additional 100 base pairs at 6 months. ”
Bob Waskom, 69
Pacific Northwest

Which differs a lot from the results that we are getting right now..

Edited by kitinje, 06 December 2009 - 06:28 PM.

[xtol]

Anyway it appears to me that telomere lengthening through the use of telomerase upregulating compounds such as ta-65/cycloastragenol could potentially be safer at a young age than in a very old one in a logic of "the younger, the better" due to mutations and dna damage that could more likely be present at an old biological state.
Ashkenazi Centenarians better maintenance of their telomeres is a lifetime long process that did not start at old age.
But this is just my opinion.


Anthony, have you switched to Cycloastragenol?
It would be nice to see your results in a few months, since nobody here has managed to really enlengthen telomeres by now,
is someone in this forum taking real TA-65?

Just to realize if their compound does really what stated on their website

“My telomeres got longer by 100 base pairs at 3 months and an additional 100 base pairs at 6 months. ”
Bob Waskom, 69
Pacific Northwest

Which differs a lot from the results that we are getting right now..

TA-65 composition seems to be what started this particular forum lo those many posts ago. A lot of inductive and deductive reasoning has gone into working out the formulation, along with actual empirical experimentation with likely candidates (A4, Cycloastraganol, and even straight astragalus extracts). It seems safe to eliminate A4 and astragalus extracts from the list as TA-65 substitutes (given their apparent lack of afficacy). The remaining likely suspect seems to be Cycloastraganol, however its candidacy was based on the assumption of a 5mg TA-65 dose. This is no longer the case, so either TA-65 is Cycloastraganol, 100mg, or it is another molecule derived from astragalus, that, by Anthony's reasoning regarding costs, must be cheaper to manufacture than Cycloastraganol.

By the way, if we are testing for TA-65 via laboratory measures of telomere length, then these tests could be taken after 3 months instead of 6 (according to the '100 base pairs every 3 months' calculus). Theoretically, Cycloastraganol could be eliminated as a candidate (or confirmed) if Anthony or anyone else were tested after 3 months taking Cycloastraganol.

[niner]

Do we know what telomere length measurement TA Sciences is using? Maybe Bob Waskom's telomeres didn't change at all, and he just got an inaccurate result on a test that made it look like they were getting longer. On the other hand, I think that there are more sophisticated tests available from some academic labs; could they be using something like that? As long as we're stuck with tests with a half kilobase variation, I don't see how we can test anything unless we spend a decade on it. If nothing else, I have even more reason to hit the gym.

[xtol]

Do we know what telomere length measurement TA Sciences is using? Maybe Bob Waskom's telomeres didn't change at all, and he just got an inaccurate result on a test that made it look like they were getting longer. On the other hand, I think that there are more sophisticated tests available from some academic labs; could they be using something like that? As long as we're stuck with tests with a half kilobase variation, I don't see how we can test anything unless we spend a decade on it. If nothing else, I have even more reason to hit the gym.

It sounds as though the Patton Protocol incorporates a repeated measures design for collecting data on customers ('subjects'). Over time then, errors should wash out, provided measurements were taken every 3 months for the duration of the TA-65 therapy.

Something puzzling about TA Sciences though, is that they present a patented 'medicine' of sorts - a therapy or intervention for the aging process, but offer no published studies in peer reviewed journals, nor, apparently, do they allow any independent research to be conducted with TA-65. For all we know, the whole TA Sciences enterprise is just a gimmick, based on the exploitation of the theoretical potential of astragalus extractions to activate telomerase in certain cells.

[Anthony_Loera]

Anthony, have you switched to Cycloastragenol?

Hi kitinje,

yes I am using Cycloastragenol now.

Cheers
A

[mikeinnaples]

So the consensus now is A4 does nothing?

[xtol]

So the consensus now is A4 does nothing?

Wouldn't say there's a consensus, especially that A4 does nothing at all. I was suggesting that A4 is not TA-65. Anthony has been taking A4 for a year (?). There seems to be nothing remarkable about his telomere tests, nor those reported by GreenPower. I'm hypothesizing here, but believe there are and have been several people on this forum, myself included, who have been consuming A4 for over 6 months, and none of us has offered much in the way of noted improvements, at least compared to the testimonials on the TA Sciences web site.

[kitinje]

So the consensus now is A4 does nothing?

A4 is proven to be a telomerase activator, but we do not know how potent it is.
Scierra sciences, a company that is reasearching for telomerase inducers states

As of November 24th, 2009:

We have screened 168,992 compounds
We have found 506 telomerase inducers
These represent 33 distinct drug families
Most potent compound = 6% of goal

Sierra sciences has independently testested TA-65 (stated in tasciences.com), and TA-65 compound is very probably included in that list.

A compound that is not very effecient does not mean it doesn't work at all, but a higher blood concentration/dosage will be needed to achieve the same results of a more effective compound at significant lower dosage.
Higher dosage means a potentially increased risk of side effects in vivo. This is probably why TA-sciences started by prescribing 5mg of TA65.

They upped the dosage from 5mg to 100mg (20x) which means:
1. Compound had no side effects at that dosage.
2. Compound concentration inside somatic cells was not enough to give results.
This is for sure, no one would up the dosage by 20x of something that works the way it should.

I agree with Anthony, TA-65 could very well be A4.
And there is a big chance that TA65/A4 is not the most potent compound out there.
Cycloastragenol could be for example a little more potent than A4.

@xtol
you have tried A4 @100mg/day for 6 months without experiencing any results, did you test telomeres length before and after the treatment?
100mg might still be not enough, but if you didn't experience any side effects this is in fact a very good news because it means that people at ta-sciences could up the dosage again if it is still not enough to reach the goal.

Question is, how much of A4-supplementation is it needed to do the job before incurring in side effects that will inevitably occour beyond a certain point?

I do not think that intergrating A4 with a little bit of cycloastragenol will have any benefit, as long as cycloastragalus does not promote A4 absorption.
A4 and cycloastragenol are two different molecules and their passive diffusion inside the cell is concentration-related.

Astragaloside IV is absorbed by typical passive diffusion mechanism.
China journal of Chinese materia medica. 01/08/2008;

In this logic, it is better a higher dosage of a less potent compound (as long as there are no side effects) than adding a bit of a little more potent compound.
But this is the right way to proceed, they slowly up the dosage of the compound they already have as long as there are no side effects, and at the same time they keep looking for a more potent compound that could do the job more efficiently at a significant lower dosage.

Selenium is also known to be a telomerase activator in vitro

Telomerase Activity and Telomerase Reverse Transcriptase Expression Induced by Selenium in Rat Hepatocytes
RI-AN YU, HUA-JIE CHENΔ, LING-FEI HE, BING CHEN and XUE-MIN CHEN

but you would need a even higher dose to make it work that will probably be toxic in vivo.

I think it would be extremely interesting if someone had a high concentration - A4 topical skin cream, to see if there are some noticeable effects.
Again the concentration of A4 is fundamental.

Edited by kitinje, 09 December 2009 - 03:14 AM.

[niner]

Do the people who signed up for the Patton Protocol when it was 5mg get their $25000 dollars back?

[kitinje]

Do the people who signed up for the Patton Protocol when it was 5mg get their $25000 dollars back?

that's a good question.... They might have extended the treatment if no results at all..

Is anyone taking higher doses of A4?
like 100mg+ ?
If someone is already planning to start/has already started with that dosage, it would be important for us to know it..

Personal remarks:
- a working, controlled, transient telomerase expression technique to enlengthen your telomeres for real.
- Calorie Restriction or development of CR mimating compounds
these particular techniques may not be very long term from now, and just these 2 combined might increase human lifespan of a huge..
hopefully long enough to get a help from Aubrey de Grey's(SENS) engineering approach.

Edited by kitinje, 09 December 2009 - 03:15 AM.