Telomerase Activator in humans

TA Science announced that it will use Geron's license to develop and market non-therapeutic products using Geron's small molecule telomerase activators.
The compound is derived from a Chinese herb(Astragalus), and activates telomerase genes in human cells. Human studies have been underway since 2005.

http://www.lef.org/n...6&Section=AGING

New Product Scientifically Battles Aging at the Cellular Level-Exclusively licensed from the Geron Corporation, TA-65 is the world's first Telomerase Activator

PR Newswire

04-09-07

NEW YORK, April 9, 2007 /PRNewswire via COMTEX/ -- Telomerase Activation Sciences, Inc. (TA Sciences) announced on March 12 its license with Geron to develop and market non-therapeutic products using Geron's small molecule telomerase activators. Now TA Sciences announces the opening of the TA Sciences Center in Manhattan where customers can purchase TA Sciences' first product, a nutraceutical containing the telomerase activating agent "TA-65."

"TA Sciences welcomes our first customers and the launch of the world's first telomerase activator product," said Noel Thomas Patton, founder of TA Sciences. "A natural consequence of aging is the shortening of telomeres (caps of DNA located at the ends of all chromosomes), which ultimately results in loss of cell function. TA-65 offers the potential of reducing or reversing telomere shortening and battles tissue and organ degeneration by rejuvenating aging cells."

TA-65 is the result of vigorous scientific research that began at Geron in 1992. Already the response from the scientific community to the news of TA Sciences' ground-breaking launch has been very enthusiastic: "Telomerase Activation is the single most promising approach to reversing the effects of aging," said Michael Fossel, MD, PhD., Clinical Professor of Medicine at Michigan State University, author, and recognized authority on aging and age- related clinical disease.

And Dr. William H. Andrews, founder of Sierra Sciences, LLC and one of the principal discoverers of the telomerase genes, said: "Cleopatra, Ponce de Leon, and untold others throughout the ages have searched for the secrets of youth. That search has been futile, until now: Telomerase Activation is the first and only scientifically sound way to approach anti- aging. TA-65 is the first product in history that has been proven to slow or reverse cellular aging. Congratulations to TA Sciences and Geron!"

On April 30, 2007 TA Sciences plans to publish the results of the Pivotal 2005 Anti-Aging Trial, which is the first ever human clinical trial of a telomerase activator. This trial shows statistical verification of the anti- aging benefits of telomerase activation.

The TA Sciences Center is located at 24 E. 64th Street in New York. The company offers its telomerase-activating products as part of the 12 month "Patton Protocol." The driver of TA Sciences' product line is the telomerase- activating small molecule "TA-65," sold under license from Geron. For more information on TA Sciences visit http://www.TASciences.com or call 888-360-8886. For more information on Geron visit http://www.Geron.com.

SOURCE TA Sciences Inc.

CONTACT: Greta Blackburn of TA Sciences Inc., cell, +1-818-634-5941

URL: http://www.tasciences.com

http://www.Geron.com

http://www.prnewswire.com www.prnewswire.com

Here is the full report of the 2005 study (I believe that I read somewhere that there is additional information that will be revealed from the study on the 30th of April).
http://www.tascience...m/ta/blum2.html

The Pivotal 2005 Anti-Aging Trial of TA-65 was a double blind, placebo controlled, 24 week study in which subjects consumed 2 or 4 tablets daily of a placebo control substance (placebo groups) for 12 weeks or 2 or 4 tablets daily of a TA-65 precursor molecule (TA-41) for 12 weeks (product groups). The product tablets each contained 10 mg of TA-41 (an Astragalus extract) along with other botanical extracts and excipients.

The placebo control tablets were essentially indistinguishable from the product tablets in appearance and taste, even when the tablet was broken. The 12 week placebo or product use period was followed by a further 12 week follow-up period. To ascertain active substance in the blood (for compliance and to better understand the relationship between TA-41 and TA-65), analytical measurements of TA-41 and TA-65 (the presumed major metabolite of TA-41) were conducted at 6 weeks and 12 weeks.

Thirty six male subjects aged 60-85 who expressed an interest in reducing the signs and symptoms of aging and who reported a gradual decline in overall energy levels at the screening visit were recruited. Subjects were randomly assigned to the placebo group (n=6 taking two placebo tablets, one in the morning, one in the evening; n=6 taking 4 placebo tablets, two in the morning, two in the evening) or the product treatment group (n=12 taking two product tablets, one in morning, one in evening; n=12 taking 4 product tablets, 2 in morning, 2 in evening). Subjects were assessed at baseline and at 6 weeks, 12 weeks and 24 weeks from the first dose of product. The full study design is described in Appendix A.

Here is a paper with evidence saying telomerase is not an oncogene:
http://www.nature.co...l/1205076a.html

There is a thread on this topic in supplements, but where as it is particularly relevant to conversations occurring here in SENS, I thought that I would open this up for discussion.

Here is the letter I received today, hey ... anyone have an extra $25000 sitting around? Maybe if we bought 1000 shares of GERN at $7.50 and and sold it at 40 in May, maybe we could make a good investment in our health and bank account.
Thank you for your recent inquiry and your interest in TA Sciences. The 12
month PATTON PROTOCOL TM is the first and only program in the exciting
field of Telomere Biology designed to help optimize our individual health
as we age, and to help prolong our "Healthspan". Here is how it works:

Clients need to visit the TA Center in New York and have extensive blood
work and other biomarkers of aging done prior to starting the PATTON
PROTOCOL. This will establish your baseline condition. About two weeks
later, when the test results are in, you will have an in-depth
consultation with our associated Anti-Aging physician to discuss your
results and assess your individual health situation. If you live outside
of the New York area, it is possible to have your consultation over the
phone.

The price for this baseline program, which would normally cost close to
$5000.00, is $2430 (our actual third party, discounted out-of-pocket
costs). This baseline evaluation is very valuable on its own as a health
and aging tool. After your initial biomarkers and consultation, you then
decide if you actually want to start the 12 month PATTON PROTOCOL.

The PATTON PROTOCOL consists of:

- A year's supply of Telomerase Activator TA-65 TM (Patents Pending). This
is a pulsed program taken daily for 3 months, then off for 3 months, and
then taken again for the next 3 months, then off again for the final 3
months.

- A repeat of the baseline blood work and biomarkers of aging at 3 months,
6 months, 9 months and 12 months, and follow-up consultations with the
Anti-Aging physician at each of those time points to track your personal
progress.

-A year's supply of our proprietary packets of other nutritional
supplements, vitamins, minerals, and herbs specially formulated for TA
Sciences. These packets, taken 2 times a day, offer a comprehensive
assortment of the most effective vitamins, minerals and herbs, available
anywhere.

- A series of monthly consultations with TA Sciences' expert Lifestyle
Counselor is also available and included, to help you optimize your
personal health and aging goals.

The price for the 12 month Protocol is $22,570.00, payable in two 6 month
installments of $11,285.00 each. We expect the benefits of Telomerase
Activation to last well beyond the initial 12 month period, but this is
leading edge technology and individual results will vary. We suggest that
clients come back one year after finishing the Protocol to have their
biomarkers re-tested and evaluated, and to discuss whether a TA
Maintenance Program at a significantly lower cost would be beneficial.

Please call me if you have any questions or would like to schedule your
biomarkers.

With Best Regards,

Greta Blackburn,
Marketing Director
TA Sciences Inc.
Phone: 212-588-8805
E-mail: gretabfit@aol.com

Wow...
We all knew molecular therapies like this one would be expensive, but 25k!

Though I suppose they're trying to reduce the brunt of the possibility that the therapy isn't going to be very successful, and if it it then they can safely market it on a much larger scale.

It's a test of an anti-aging hypothesis that I've wondered about for some time: "If you make it, they will come."

Clients need to visit the TA Center in New York and have extensive blood
work and other biomarkers of aging done...

I would love to know what these biomarkers are!

A year's supply of our proprietary packets of other nutritional
supplements, vitamins, minerals, and herbs specially formulated for TA
Sciences. These packets, taken 2 times a day, offer a comprehensive
assortment of the most effective vitamins, minerals and herbs, available
anywhere.

Uhhh, this makes this sound like a major scam. Why would you introduce additional variables into a trial?

I'm not sure if that counts as the addition of variables.

It makes sense to me that even in a trial, they're going to want to get people in as good of functional shape as they can get them, and biologically this means supplements and nutrition. By exposing the sample size to this constant set of positive supplements, they can measure the effect of telomere elongation/maintanence induced by the drug.

In order for it to be a true 'test' of the like you are mentioning, they would need a double blind with a placebo, but that's definately not what they're looking for here. They want to show that their product can perform the task it was designed for, and that its function does not overlap with currently available supplements.

PS: 25 grand for a placebo would suck!

PS: 25 grand for a placebo would suck!

Not if it makes you live longer ;-)

looks like a deception

http://groups.google...020fce84318ff2d
http://groups.google...0eaeb100a092bc2
http://www.altbaldsp...pic.php?p=96671

no scientific evidence

Hmm....
This definately does deserve an eye of skepticism.
This TA-65 enzyme they are touting is a telomerase activating protein, apparently originally found by Geron (I assume, since they seem to have the patents on the molecule and the patent has been 'leased' to TASciences).

TA-65 is a purified extract from a plant that has been used safely as a Traditional Chinese herb for thousands of years. This powerful ingredient is the only substance commercially available that activates (turns on) telomerase.

The herb is called Astragalus.

I gave a fake phone number and real email address to the TA website so that I could poke around in it.

http://www.tasciences.com/ta/blum.html

I don't know if there are barriers to entry if you haven't registered but I encourage you to take a look.

The problem I see is a lack of in vitro and biochemical assays. However, they were legitimate enough to do double blind palcebo experiments.

I don't immediately dismiss it, but the product begs a few important questions.

Concentration to be effective?
Quantitative elongation of telomeres?
How much is naturally present in the herb?
BIOCHEMICAL ASSAYS?

However, they were legitimate enough to do double blind palcebo experiments.

The p-values of the expiriment were huge: some as high as .75
The big thing is that they haven't tested for telomere lengthening or telomerase activation directly in any study that I have read...

The p-values of the expiriment were huge: some as high as .75
The big thing is that they haven't tested for telomere lengthening or telomerase activation directly in any study that I have read...

Well, they were pretty up-front about labeling the high p-value stuff as "trends" or some such. I didn't feel misled by it. The data wasn't all high p-value. Somebody must have actually looked at telomere lengthening / telomerase activation. If no one had looked at it, why would these guys have (as someone said) licensed the patent from Geron? IMHO, one of the key experiments in humans will be to look not just at telomere lengthening, but tissue distribution of the effects. It sure sucks that something with such seeming promise would wind up in the hands of people who at least give the appearance of acting like clueless shysters. Is this appearance problem simply a function of them trying to make tons of money off of a genuinely revolutionary therapy? Or are they just crooks? At this point my hopeful nature leans toward the former, but the cynic in me doesn't yet rule out the latter.

Can anyone answer my following questions on telomerase:

1. By activating the telomerase in the senesecent cells which has undergone damage in Mitochondria, has lipofuscin, etc...the new cell formed by multiplication has all the damages reversed or removed to form young cells?
2. I have seen literature of Prof.Shay and Wright on extending the telomerase in animals..Do they live longer? Link to Shay and Wright lab is given below:

http://www4.utsouthw...ight/index.html

Links to the patents of Astragalus activation on Telomerase (thanks to the link presented in google groups on life extension by jc101)

http://tinyurl.com/2yypov
http://tinyurl.com/3db889

Links to the patents of Astragalus activation on Telomerase (thanks to the link presented in google groups on life extension by jc101)

http://tinyurl.com/2yypov
http://tinyurl.com/3db889

Those links produce PDF files that appear to have only the title page.

Here is a link to the first document on the WIPO site. The second seems to have been withdrawn:

http://www.wipo.int/...p?wo=2005000245

Can anyone answer my following questions on telomerase:

1. By activating the telomerase in the senesecent cells which has undergone damage in Mitochondria, has lipofuscin, etc...the new cell formed by multiplication has all the damages reversed or removed to form young cells?
2. I have seen literature of Prof.Shay and Wright on extending the telomerase in animals..Do they live longer? Link to Shay and Wright lab is given below:

http://www4.utsouthw...ight/index.html

The answer to question one is absolutely not. They will pass on their accumulated genetic damage to their daughter cells. Damaged materials not encoding information, ie proteins and lipids, will be diluted or replaced, depending on their turnover rate in mitotic cells.

The answer to question one is absolutely not.

That is not absolutely true. While all of the complicated functions of telomerase are not fully understood. There are studies showing that telomerase induces apoptosis, additionally, (I don't have a study to back this claim up, it is more of an observation) the body normally cleanses it's soma by destroying damaged cells and replacing them with healthy cells. When cells become senescent and lose their reproductive capacity, that is also when the soma stops cleansing and will leave behind damaged cells. It is possible that by reintroducing telomerase, lots of the damaged cells could die off leaving more healthy cells behind.

No, my answer is correct. Go back and re-read his question. You missed his point. He asked specifically, if a cell with damaged DNA is taken out of senescence and begins replicating, will the DNA be restored to its original state. The answer still is no.

To address your other points, terminally differentiated tissues are not as a rule destroyed when they become damaged, unless that damage is quite severe. This is because the threshold for their becoming cancerous is much higher than that of actively mitotic cells. Horeover, most of these cells are irreplaceable or not efficiently replaceable, and destroying them will cause serious deleterious effects, like brain damage or heart failure. If all the damaged, senescent cells in your brain suddenly underwent apoptosis, you'd be seriously screwed, and they would not be replaced.

That is not absolutely true. While all of the complicated functions of telomerase are not fully understood. There are studies showing that telomerase induces apoptosis, additionally, (I don't have a study to back this claim up, it is more of an observation) the body normally cleanses it's soma by destroying damaged cells and replacing them with healthy cells. When cells become senescent  and lose their reproductive capacity, that is also when the soma stops cleansing and will leave behind damaged cells. It is possible that by reintroducing telomerase, lots of the damaged cells could die off leaving more healthy cells behind.

The use of resveratrol to activate NOS to produce more mitochondrial biogenesis even in old mice (David sinclair's work) thus leading to life span extension prove the possibility of generating more functional mitochondrias even in old mice. If just activating telomerase does not lead to more functional mitochondrias, does the combo with compounds like resveratrol would reverse the damage and improve the longevity of the cell?

What astonishes me is that this research was announced 4 months ago and has not yet reached the mainstream media. I have followed longevity research for 25 years and this is waaay bigger news than Growth Hormone or Glycation Bond Breakers (ALT-711), Resveratrol/sir2P gene activation, or farnesyl transferase inhibitors or anything else that has been discovered in the past quarter century. If you read the patents and realize what is actually being claimed... well it boggles the mind. This could really be it. A naturally occuring, non-patentable substance that kicks the Hayflick Limit into the next century. Will I take this stuff? Absofuckinglutely. Already do as a matter of fact. 1500 mg a day of standardized Astragalus exract standardized to 0.4% (20mg) of 4hydroxy 3 methoxyisoflavone. Cost is about 50 cents a day...LOL Now does this extract contain the proper astrogaloside or whatever TA-65 is? No way of knowing without obtaining a sample of TA-65 and running a comparison to the readily available Astragalus extracts. I am willing to bet it does however based on my read of the patent. It's just a simple ethanolic extraction and hey if I get other compounds so much the better. There is NOTHING in the literature to indicate any untoward effects from Astragalus extract. Been used for several THOUSAND years by the Chinese.

The principle compound, astragaloside IV, is typically found at 0.15 mg/g in astragalus root. A typical dose of TA-65 is 5 mg, equivilant to 5mg/0.15mg/g = 33.33 grams of Astragalus root if it is astragaloside IV, while the typical maximum dose of Astragalus root used in treatment is 30 grams. However, since Geron prescribes astragaloside IV at 50 mg to 100 mg and cycloastragenol at 5 mg, it is far more likely that TA-65 is cycloastragenol. [See Links/Astragaloside IV, Source Chengdu Cogon Biotech, Chinese sources, Books/Astragaloside IV.] A Geron patent cites astragaloside IV as one embodiment of a formula for a telomerase activator. Geron's European patent describes other telomerase activators from astragalus root extract including cycloastragenol, astragenol, and astragaloside IV 16-one.

Another basic question, I have, what makes a cell to divide? Does it require enough mitochondrial mutation, lipofuscin to happen or even younger cells which has less or negligible mutations or lipofuscin also divide (i would assume, that is the case, since, during the initial stages of growth of a baby, the cells divide pretty fast). If my hypothesis is correct, then increasing telomerase should definitely minimize the lipofuscin since, it is now getting distributed to higher number of cells (due to replication), so that senescence can be delayed? Any counter explanations is welcome?

ganeshge: I hope you get a good answer from a much more knowledgeable person here but for the time being it would like to suggest that the SOS hypothesis might shed some light on it.

I found out about it when I was trying to find out if there was a highly error prone method of DNA repair and I found out about TLS.

Here is the pubmed entry for the SOS hypothesis:
http://www.ncbi.nlm....pt=AbstractPlus

I don't understand it all myself, just trying to put all the pieces together.

TA-65 is probably cycloastragenol, judging from Geron's intellectual property documents.
Cycloastragenol is the common alglycone of the astragalosides and the smallest molecule
telomerase activator in astragalus extract. Astragaloside iv has also been tested by Geron
for telomerase activation, but is prescribed at 50-100 mg/day instead of 5 mg/day.
Also, we need more testing of commercially available astragalus extracts rich in astragalosides
such as GAIA Astragalus Extract, which features 1 mg of astragalosides per 30 drops in their
ethanolic astragalus extract. I have been experimenting since May 2007 with 5 mg/day of
astragalosides from GAIA Astragalus Extracts, with fairly good initial results. Eventually
it may be possible with this approach to largely eliminate senescent cells in the body and
reset gene expression to youthful levels for endogenous antioxidants, elastin, collagen, and
other important compounds. I am careful to eliminate telomerase inhibitors such as melatonin,
curcumin, resveratrol, quercetin, green tea, and vitamin E for two weeks while using 5 mg/day
astragalosides, then I switch back for two weeks to plenty of these supplements. This way,
I can catch any cancer cells during the 2nd two weeks of the cycle, but get the benefit of extra
genetic stability against cancer than comes from eliminating senescent cells by lengthening
telomeres with the astragalosides. As far as I know, nothing else currently on the shelf at the health
food store works as well against cellular senescence as well as astragalus extracts. Other drugs just slow
telomere erosion down. Astragalus extracts lenthen telomeres until the t-loops close at the ends of
the telomere and cells return to the pre-senescent immortal phenotype, eventually resetting gene
expression to youthful levels. I get the impression that the maximum benefit from this sort of thing
is about 9 years backwards in time per year of astrogaloside treatment, until you obtain the immortal
phenotype and seem to hang on looking about 28. That is about what my calculations based on
TA Sciences data show can be done with TA-65. I expect I am getting worse results with simple astragalus
extract, but it does seem to be impacting my hair coloration and be reducing the number of grey hairs by
reviving senescent stem cells. More careful scientific studies of readily available astragalus extracts
are definitely in order, both in vivo and on in vitro cell cultures. Astragalus has great low toxicity properties,
accelerates wound healing, lengthens telomeres, is available in glycerin for direct application to skin,
and has been used for a long time to fight B-cell senescence yielding lymphoma night sweats,
being the first effective cure for night sweats found centuries ago. We need more studies to determine
how well astragalus extracts work against senescence in different kinds of cells, and to determine how
fast we may expect to obtain results. A year of my program costs about $225 in my neighborhood,
but I have not got set up yet to do actual telomere length measurements or telomerase activation studies
in connection with these initial probings.
I might add that Vasa, et.al, determined that NO activation lengthens telomeres in endothelial cells.
Exercise increases nitric oxide synthetase levels greatly, and generates the required NO in presence
of arginine, say from bodybuilder's protein powder. Thus bodybuilding with NO supplements refreshes
the vascular endothelium with telomerase activation effect.

Edited by jamesagreen, 25 January 2008 - 07:13 PM.

Astragalus extracts lenthen telomeres until the t-loops close at the ends of the telomere and cells return to the pre-senescent immortal phenotype, eventually resetting gene expression to youthful levels. I get the impression that the maximum benefit from this sort of thing is about 9 years backwards in time per year of astrogaloside treatment, until you obtain the immortal phenotype and seem to hang on looking about 28. That is about what my calculations based on TA Sciences data show can be done with TA-65. I expect I am getting worse results with simple astragalus extract, but it does seem to be impacting my hair coloration and be reducing the number of grey hairs by reviving senescent stem cells. More careful scientific studies of readily available astragalus extracts are definitely in order, both in vivo and on in vitro cell cultures.

James, thanks for all the information. I'm wondering about the quoted part here, because it seems to me that if a cell has become senescent due to telomere shortness, and it then gets its telomeres extended and (presumably) becomes un-senescent, isn't it still saddled with all the injuries that it sustained over its life? In other words, it may still have sagging, leaky old mitochondria... Likewise, the extracellular matrix will still have whatever glycoxidation it already had, and all the old lipofuscin bodies will still be there. I don't see how lengthening telomeres alone can take you back to 28, unless maybe you are 27 when you start. It does make sense to me that telomerase activation might make a 90-year-old feel 80 again, but not 27. Is the impact on you hair coloration very noticeable? You look fairly young from your picture; do young people have enough cells with depleted telomeres to make a program like this worthwhile? I figure that I'll wait until I'm 65 to try TA-65, but is that the wrong approach?

Astragalus extracts lenthen telomeres until the t-loops close at the ends of the telomere and cells return to the pre-senescent immortal phenotype, eventually resetting gene expression to youthful levels. I get the impression that the maximum benefit from this sort of thing is about 9 years backwards in time per year of astrogaloside treatment, until you obtain the immortal phenotype and seem to hang on looking about 28. That is about what my calculations based on TA Sciences data show can be done with TA-65. I expect I am getting worse results with simple astragalus extract, but it does seem to be impacting my hair coloration and be reducing the number of grey hairs by reviving senescent stem cells. More careful scientific studies of readily available astragalus extracts are definitely in order, both in vivo and on in vitro cell cultures.

James, thanks for all the information. I'm wondering about the quoted part here, because it seems to me that if a cell has become senescent due to telomere shortness, and it then gets its telomeres extended and (presumably) becomes un-senescent, isn't it still saddled with all the injuries that it sustained over its life? In other words, it may still have sagging, leaky old mitochondria... Likewise, the extracellular matrix will still have whatever glycoxidation it already had, and all the old lipofuscin bodies will still be there. I don't see how lengthening telomeres alone can take you back to 28, unless maybe you are 27 when you start. It does make sense to me that telomerase activation might make a 90-year-old feel 80 again, but not 27. Is the impact on you hair coloration very noticeable? You look fairly young from your picture; do young people have enough cells with depleted telomeres to make a program like this worthwhile? I figure that I'll wait until I'm 65 to try TA-65, but is that the wrong approach?

(Reply, March 20, 2008)
Lengthening telomeres results in more youthful patterns of gene expression from nuclear DNA, resulting in higher expression
levels for endogenous antioxidants, collagen, elastin, and other factors promoting youthful cell function and resulting in the
display of the immortal phenotype. Furthermore, it confers genetic stability on the cell tending to protect it from cancer, because
cancer often occurs due to end-point fusions when telomeres get disasterously short. Keeping the telomeres long keeps the
cell from activating a DNA damage checkpoint. The result is that cells seem to be relatively immune to free radical and
glycation damage by comparison with senescent cells. This is why cells can be immoralized with telomerase activation
in vitro in many cases. In reality, the time to take TA-65 or ethanolic astragalus extracts (perhaps in glycerin) to
activate telomerase is right about the time hairs turn grey. The greying of hairs tracks the death rate curves very well,
and corresponds to the population of senescent cells in the body, reflecting the senescence of stem cells that rejuvenate
grey hairs. So take TA-65 or astragalus extract to minimize the senescent cell population leading to cancer, heart attack,
stroke, macular degeneration, and so forth just as soon as grey hairs show up. They mirror the senescent cell population
supporting diseases of old age. That way we can hug the baseline of the death rate chart way out to several hundred
years or more, perhaps. Of course, it is clear that lipofuscin or ceroid removal in old people had better proceed in
parallel with small molecule telomerase activator treatments. For this lipofuscin removal task alpha lipoic acid, Piracetam, ubiquinol CoQ10,
old-fashioned ubiquinone CoQ10, and other drugs have been identified. Just lengthening the telomeres helps a lot more than
seems reasonable, however, as youthful patterns of gene expression include more collagen and elastin, which slowly
restore old tissue to its former youthful appearance. Bear in mind that restoration of the extracellular matrix by the
technique of telomerase activation takes a little longer than the restoration of hair color due to lengthening stem cell
telomeres. However, it works. You can see the difference in home movies after 9 months of 5 mg/day GAIA astragalosides
from GAIA astragalus extract, requiring about 150 drops per day during the two-week activation period in which you
avoid telomerase inhibitors such as curcumin (turmeric), silymarin, garlic (allicin), melatonin, vitamin E, fish oil EPA,
resveratrol, and quercetin. These telomerase inhibitors can be taken during the next two weeks, before starting
all over again. After 11 months, the results look like 9 years per year backwards in time, about like we expect for
TA-65 based on reports of 460 bp per year, about 77 TTAGGG sequences per year, or approximately 45 twists of
the Watson-Crick DNA-B helix. However, results should become more dramatic as time goes on, because
after a year, 59 looks like 50, then theoretically 60 looks like 41, after which 61 looks like 32, and so on.
The effect is you get a Time Machine feeling about like something out of HG Wells, because of the cumulative
effect on the cells. TA-65's advantage may be merely chemical purity, so that our knowledge becomes more
precise, eventually. Or perhaps it works a bit faster, because in regular astragalus extract, we use the slightly
larger molecule astragaloside IV, primarily. Anyway, while using such a program, it is important to go ahead
and continue to work against glycation and free radical damage using carnosine, antioxidants, and vitamin C.
As for mitochondria, NO activation using bodybuilding exercises with arginine-enriched whey protein should
help revive mitochondria, which anyway turn over pretty rapidly, approximately every 14 days, if memory
serves. NO activation via the action of nitric oxide synthase on arginine also has the effect of activating telomerase in the vascular endothelium, according to
Vasa, et al., 2000, and Hayashi, et al., 2006, and of promoting mitochondrial biogenesis. Saving hair samples and counting grey hairs seems to be a poor
substitute for actually measuring telomere growth, but it is definitely easier on your bank account. I would say
that the difference in my gray hair levels is striking, especially when I get of the shower in the morning with
a head of wet hair, which tends to make it look darker, anyway. Perhaps this is why baptism was so popular, in fact.
I recommend preparing hair clippings from the top, the sides, and the back of the head when doing this experiment,
and filing them in envelopes for counts later. Mine looks like a case of salt and pepper got darker, and I am optimistic
about the future course of this treatment. Incidentally, the little picture of me on this web page looks like I looked with my hair dyed in 2001.

Edited by jamesagreen, 20 March 2008 - 07:35 PM.

Astragalus extracts lenthen telomeres until the t-loops close at the ends of the telomere and cells return to the pre-senescent immortal phenotype, eventually resetting gene expression to youthful levels. I get the impression that the maximum benefit from this sort of thing is about 9 years backwards in time per year of astrogaloside treatment, until you obtain the immortal phenotype and seem to hang on looking about 28. That is about what my calculations based on TA Sciences data show can be done with TA-65. I expect I am getting worse results with simple astragalus extract, but it does seem to be impacting my hair coloration and be reducing the number of grey hairs by reviving senescent stem cells. More careful scientific studies of readily available astragalus extracts are definitely in order, both in vivo and on in vitro cell cultures.

James, thanks for all the information. I'm wondering about the quoted part here, because it seems to me that if a cell has become senescent due to telomere shortness, and it then gets its telomeres extended and (presumably) becomes un-senescent, isn't it still saddled with all the injuries that it sustained over its life? In other words, it may still have sagging, leaky old mitochondria... Likewise, the extracellular matrix will still have whatever glycoxidation it already had, and all the old lipofuscin bodies will still be there. I don't see how lengthening telomeres alone can take you back to 28, unless maybe you are 27 when you start. It does make sense to me that telomerase activation might make a 90-year-old feel 80 again, but not 27. Is the impact on you hair coloration very noticeable? You look fairly young from your picture; do young people have enough cells with depleted telomeres to make a program like this worthwhile? I figure that I'll wait until I'm 65 to try TA-65, but is that the wrong approach?

(Reply, March 20, 2008)
Lengthening telomeres results in more youthful patterns of gene expression from nuclear DNA, resulting in higher expression
levels for endogenous antioxidants, collagen, elastin, and other factors promoting youthful cell function and resulting in the
display of the immortal phenotype. Furthermore, it confers genetic stability on the cell tending to protect it from cancer, because
cancer often occurs due to end-point fusions when telomeres get disasterously short. Keeping the telomeres long keeps the
cell from activating a DNA damage checkpoint. The result is that cells seem to be relatively immune to free radical and
glycation damage by comparison with senescent cells. This is why cells can be immoralized with telomerase activation
in vitro in many cases. In reality, the time to take TA-65 or ethanolic astragalus extracts (perhaps in glycerin) to
activate telomerase is right about the time hairs turn grey. The greying of hairs tracks the death rate curves very well,
and corresponds to the population of senescent cells in the body, reflecting the senescence of stem cells that rejuvenate
grey hairs. So take TA-65 or astragalus extract to minimize the senescent cell population leading to cancer, heart attack,
stroke, macular degeneration, and so forth just as soon as grey hairs show up. They mirror the senescent cell population
supporting diseases of old age. That way we can hug the baseline of the death rate chart way out to several hundred
years or more, perhaps. Of course, it is clear that lipofuscin or ceroid removal in old people had better proceed in
parallel with small molecule telomerase activator treatments. For this lipofuscin removal task alpha lipoic acid, Piracetam, ubiquinol CoQ10,
old-fashioned ubiquinone CoQ10, and other drugs have been identified. Just lengthening the telomeres helps a lot more than
seems reasonable, however, as youthful patterns of gene expression include more collagen and elastin, which slowly
restore old tissue to its former youthful appearance. Bear in mind that restoration of the extracellular matrix by the
technique of telomerase activation takes a little longer than the restoration of hair color due to lengthening stem cell
telomeres. However, it works. You can see the difference in home movies after 9 months of 5 mg/day GAIA astragalosides
from GAIA astragalus extract, requiring about 150 drops per day during the two-week activation period in which you
avoid telomerase inhibitors such as curcumin (turmeric), silymarin, garlic (allicin), melatonin, vitamin E, fish oil EPA,
resveratrol, and quercetin. These telomerase inhibitors can be taken during the next two weeks, before starting
all over again. After 11 months, the results look like 9 years per year backwards in time, about like we expect for
TA-65 based on reports of 460 bp per year, about 77 TTAGGG sequences per year, or approximately 45 twists of
the Watson-Crick DNA-B helix. However, results should become more dramatic as time goes on, because
after a year, 59 looks like 50, then theoretically 60 looks like 41, after which 61 looks like 32, and so on.
The effect is you get a Time Machine feeling about like something out of HG Wells, because of the cumulative
effect on the cells. TA-65's advantage may be merely chemical purity, so that our knowledge becomes more
precise, eventually. Or perhaps it works a bit faster, because in regular astragalus extract, we use the slightly
larger molecule astragaloside IV, primarily. Anyway, while using such a program, it is important to go ahead
and continue to work against glycation and free radical damage using carnosine, antioxidants, and vitamin C.
As for mitochondria, NO activation using bodybuilding exercises with arginine-enriched whey protein should
help revive mitochondria, which anyway turn over pretty rapidly, approximately every 14 days, if memory
serves. NO activation via the action of nitric oxide synthase on arginine also has the effect of activating telomerase in the vascular endothelium, according to
Vasa, et al., 2000, and Hayashi, et al., 2006, and of promoting mitochondrial biogenesis. Saving hair samples and counting grey hairs seems to be a poor
substitute for actually measuring telomere growth, but it is definitely easier on your bank account. I would say
that the difference in my gray hair levels is striking, especially when I get of the shower in the morning with
a head of wet hair, which tends to make it look darker, anyway. Perhaps this is why baptism was so popular, in fact.
I recommend preparing hair clippings from the top, the sides, and the back of the head when doing this experiment,
and filing them in envelopes for counts later. Mine looks like a case of salt and pepper got darker, and I am optimistic
about the future course of this treatment. Incidentally, the little picture of me on this web page looks like I looked with my hair dyed in 2001.

Astragalus extracts lenthen telomeres until the t-loops close at the ends of the telomere and cells return to the pre-senescent immortal phenotype, eventually resetting gene expression to youthful levels. I get the impression that the maximum benefit from this sort of thing is about 9 years backwards in time per year of astrogaloside treatment, until you obtain the immortal phenotype and seem to hang on looking about 28. That is about what my calculations based on TA Sciences data show can be done with TA-65. I expect I am getting worse results with simple astragalus extract, but it does seem to be impacting my hair coloration and be reducing the number of grey hairs by reviving senescent stem cells. More careful scientific studies of readily available astragalus extracts are definitely in order, both in vivo and on in vitro cell cultures.

James, thanks for all the information. I'm wondering about the quoted part here, because it seems to me that if a cell has become senescent due to telomere shortness, and it then gets its telomeres extended and (presumably) becomes un-senescent, isn't it still saddled with all the injuries that it sustained over its life? In other words, it may still have sagging, leaky old mitochondria... Likewise, the extracellular matrix will still have whatever glycoxidation it already had, and all the old lipofuscin bodies will still be there. I don't see how lengthening telomeres alone can take you back to 28, unless maybe you are 27 when you start. It does make sense to me that telomerase activation might make a 90-year-old feel 80 again, but not 27. Is the impact on you hair coloration very noticeable? You look fairly young from your picture; do young people have enough cells with depleted telomeres to make a program like this worthwhile? I figure that I'll wait until I'm 65 to try TA-65, but is that the wrong approach?

(Reply, March 20, 2008)
Lengthening telomeres results in more youthful patterns of gene expression from nuclear DNA, resulting in higher expression
levels for endogenous antioxidants, collagen, elastin, and other factors promoting youthful cell function and resulting in the
display of the immortal phenotype. Furthermore, it confers genetic stability on the cell tending to protect it from cancer, because
cancer often occurs due to end-point fusions when telomeres get disasterously short. Keeping the telomeres long keeps the
cell from activating a DNA damage checkpoint. The result is that cells seem to be relatively immune to free radical and
glycation damage by comparison with senescent cells. This is why cells can be immoralized with telomerase activation
in vitro in many cases. In reality, the time to take TA-65 or ethanolic astragalus extracts (perhaps in glycerin) to
activate telomerase is right about the time hairs turn grey. The greying of hairs tracks the death rate curves very well,
and corresponds to the population of senescent cells in the body, reflecting the senescence of stem cells that rejuvenate
grey hairs. So take TA-65 or astragalus extract to minimize the senescent cell population leading to cancer, heart attack,
stroke, macular degeneration, and so forth just as soon as grey hairs show up. They mirror the senescent cell population
supporting diseases of old age. That way we can hug the baseline of the death rate chart way out to several hundred
years or more, perhaps. Of course, it is clear that lipofuscin or ceroid removal in old people had better proceed in
parallel with small molecule telomerase activator treatments. For this lipofuscin removal task alpha lipoic acid, Piracetam, ubiquinol CoQ10,
old-fashioned ubiquinone CoQ10, and other drugs have been identified. Just lengthening the telomeres helps a lot more than
seems reasonable, however, as youthful patterns of gene expression include more collagen and elastin, which slowly
restore old tissue to its former youthful appearance. Bear in mind that restoration of the extracellular matrix by the
technique of telomerase activation takes a little longer than the restoration of hair color due to lengthening stem cell
telomeres. However, it works. You can see the difference in home movies after 9 months of 5 mg/day GAIA astragalosides
from GAIA astragalus extract, requiring about 150 drops per day during the two-week activation period in which you
avoid telomerase inhibitors such as curcumin (turmeric), silymarin, garlic (allicin), melatonin, vitamin E, fish oil EPA,
resveratrol, and quercetin. These telomerase inhibitors can be taken during the next two weeks, before starting
all over again. After 11 months, the results look like 9 years per year backwards in time, about like we expect for
TA-65 based on reports of 460 bp per year, about 77 TTAGGG sequences per year, or approximately 45 twists of
the Watson-Crick DNA-B helix. However, results should become more dramatic as time goes on, because
after a year, 59 looks like 50, then theoretically 60 looks like 41, after which 61 looks like 32, and so on.
The effect is you get a Time Machine feeling about like something out of HG Wells, because of the cumulative
effect on the cells. TA-65's advantage may be merely chemical purity, so that our knowledge becomes more
precise, eventually. Or perhaps it works a bit faster, because in regular astragalus extract, we use the slightly
larger molecule astragaloside IV, primarily. Anyway, while using such a program, it is important to go ahead
and continue to work against glycation and free radical damage using carnosine, antioxidants, and vitamin C.
As for mitochondria, NO activation using bodybuilding exercises with arginine-enriched whey protein should
help revive mitochondria, which anyway turn over pretty rapidly, approximately every 14 days, if memory
serves. NO activation via the action of nitric oxide synthase on arginine also has the effect of activating telomerase in the vascular endothelium, according to
Vasa, et al., 2000, and Hayashi, et al., 2006, and of promoting mitochondrial biogenesis. Saving hair samples and counting grey hairs seems to be a poor
substitute for actually measuring telomere growth, but it is definitely easier on your bank account. I would say
that the difference in my gray hair levels is striking, especially when I get of the shower in the morning with
a head of wet hair, which tends to make it look darker, anyway. Perhaps this is why baptism was so popular, in fact.
I recommend preparing hair clippings from the top, the sides, and the back of the head when doing this experiment,
and filing them in envelopes for counts later. Mine looks like a case of salt and pepper got darker, and I am optimistic
about the future course of this treatment. Incidentally, the little picture of me on this web page looks like I looked with my hair dyed in 2001.
As of March 2009, I have been substituting 6 x 200 mg/day Solaray Astragalus Root Extract to approach the 5 mg/day
that I was formerly getting with GAIA Astragalus Root Extract before they modified their formula, cutting the
content of astragalosides. Although this dosage is more than Solaray recommends, it satisfies my toxicology
checks and approached 5 mg/day astragalosides in initial calculations based on papers showing the composiition
of ethanolic astragalus extracts and on Solaray Astragalus Root Extract composiiton according to Solaray.

TA-65 is probably cycloastragenol, judging from Geron's intellectual property documents.
Cycloastragenol is the common alglycone of the astragalosides and the smallest molecule
telomerase activator in astragalus extract. Astragaloside iv has also been tested by Geron
for telomerase activation, but is prescribed at 50-100 mg/day instead of 5 mg/day.
Also, we need more testing of commercially available astragalus extracts rich in astragalosides
such as GAIA Astragalus Extract, which features 1 mg of astragalosides per 30 drops in their
ethanolic astragalus extract. I have been experimenting since May 2007 with 5 mg/day of
astragalosides from GAIA Astragalus Extracts, with fairly good initial results. Eventually
it may be possible with this approach to largely eliminate senescent cells in the body and
reset gene expression to youthful levels for endogenous antioxidants, elastin, collagen, and
other important compounds. I am careful to eliminate telomerase inhibitors such as melatonin,
curcumin, resveratrol, quercetin, green tea, and vitamin E for two weeks while using 5 mg/day
astragalosides, then I switch back for two weeks to plenty of these supplements. This way,
I can catch any cancer cells during the 2nd two weeks of the cycle, but get the benefit of extra
genetic stability against cancer than comes from eliminating senescent cells by lengthening
telomeres with the astragalosides. As far as I know, nothing else currently on the shelf at the health
food store works as well against cellular senescence as well as astragalus extracts. Other drugs just slow
telomere erosion down. Astragalus extracts lenthen telomeres until the t-loops close at the ends of
the telomere and cells return to the pre-senescent immortal phenotype, eventually resetting gene
expression to youthful levels. I get the impression that the maximum benefit from this sort of thing
is about 9 years backwards in time per year of astrogaloside treatment, until you obtain the immortal
phenotype and seem to hang on looking about 28. That is about what my calculations based on
TA Sciences data show can be done with TA-65. I expect I am getting worse results with simple astragalus
extract, but it does seem to be impacting my hair coloration and be reducing the number of grey hairs by
reviving senescent stem cells. More careful scientific studies of readily available astragalus extracts
are definitely in order, both in vivo and on in vitro cell cultures. Astragalus has great low toxicity properties,
accelerates wound healing, lengthens telomeres, is available in glycerin for direct application to skin,
and has been used for a long time to fight B-cell senescence yielding lymphoma night sweats,
being the first effective cure for night sweats found centuries ago. We need more studies to determine
how well astragalus extracts work against senescence in different kinds of cells, and to determine how
fast we may expect to obtain results. A year of my program costs about $225 in my neighborhood,
but I have not got set up yet to do actual telomere length measurements or telomerase activation studies
in connection with these initial probings.
I might add that Vasa, et.al, determined that NO activation lengthens telomeres in endothelial cells.
Exercise increases nitric oxide synthetase levels greatly, and generates the required NO in presence
of arginine, say from bodybuilder's protein powder. Thus bodybuilding with NO supplements refreshes
the vascular endothelium with telomerase activation effect. Following the recommendation of Nobelist
Louis B. Ignarro, I use 5 mg arginine per day with 1 gram of L-citrulline per day with exercise to stimulte
the production of nitric oxide.
Since March 2009, I have been substituting 6 x 200 mg/day Solaray Astragalus Root Extract, that is, 1200 mg/day Solaray
Astragalus Root Extract, to replace GAIA Astragalus Root Extract, which changed in its composition to a weaker
formula I computed to be 1/13th its former strength. Although this is a higher dose than Solaray recommends,
it satisfies my toxicology checks and in initial calculations made the 5 mg/day astragaloside dose that I am experimenting
with available. Note that this requires 3 bottles of Solaray Astragalus Root Extract per month, six 200 mg capsules
per day, for a cost about the same as formerly paid for GAIA Herbs Astragalus Root Extract. This lasts for
15 days, so that one uses 15 days on, 15 days off.

Edited by jamesagreen, 24 March 2009 - 05:12 PM.

TA-65 is probably cycloastragenol, judging from Geron's intellectual property documents.
Cycloastragenol is the common alglycone of the astragalosides and the smallest molecule
telomerase activator in astragalus extract. Astragaloside iv has also been tested by Geron
for telomerase activation, but is prescribed at 50-100 mg/day instead of 5 mg/day.
Also, we need more testing of commercially available astragalus extracts rich in astragalosides
such as GAIA Astragalus Extract, which features 1 mg of astragalosides per 30 drops in their
ethanolic astragalus extract. I have been experimenting since May 2007 with 5 mg/day of
astragalosides from GAIA Astragalus Extracts, with fairly good initial results. Eventually
it may be possible with this approach to largely eliminate senescent cells in the body and
reset gene expression to youthful levels for endogenous antioxidants, elastin, collagen, and
other important compounds. I am careful to eliminate telomerase inhibitors such as melatonin,
curcumin, resveratrol, quercetin, green tea, and vitamin E for two weeks while using 5 mg/day
astragalosides, then I switch back for two weeks to plenty of these supplements. This way,
I can catch any cancer cells during the 2nd two weeks of the cycle, but get the benefit of extra
genetic stability against cancer than comes from eliminating senescent cells by lengthening
telomeres with the astragalosides. As far as I know, nothing else currently on the shelf at the health
food store works as well against cellular senescence as well as astragalus extracts. Other drugs just slow
telomere erosion down. Astragalus extracts lenthen telomeres until the t-loops close at the ends of
the telomere and cells return to the pre-senescent immortal phenotype, eventually resetting gene
expression to youthful levels. I get the impression that the maximum benefit from this sort of thing
is about 9 years backwards in time per year of astrogaloside treatment, until you obtain the immortal
phenotype and seem to hang on looking about 28. That is about what my calculations based on
TA Sciences data show can be done with TA-65. I expect I am getting worse results with simple astragalus
extract, but it does seem to be impacting my hair coloration and be reducing the number of grey hairs by
reviving senescent stem cells. More careful scientific studies of readily available astragalus extracts
are definitely in order, both in vivo and on in vitro cell cultures. Astragalus has great low toxicity properties,
accelerates wound healing, lengthens telomeres, is available in glycerin for direct application to skin,
and has been used for a long time to fight B-cell senescence yielding lymphoma night sweats,
being the first effective cure for night sweats found centuries ago. We need more studies to determine
how well astragalus extracts work against senescence in different kinds of cells, and to determine how
fast we may expect to obtain results. A year of my program costs about $225 in my neighborhood,
but I have not got set up yet to do actual telomere length measurements or telomerase activation studies
in connection with these initial probings.
I might add that Vasa, et.al, determined that NO activation lengthens telomeres in endothelial cells.
Exercise increases nitric oxide synthetase levels greatly, and generates the required NO in presence
of arginine, say from bodybuilder's protein powder. Thus bodybuilding with NO supplements refreshes
the vascular endothelium with telomerase activation effect. Following the recommendation of Nobelist
Louis B. Ignarro, I use 5 mg arginine per day with 1 gram of L-citrulline per day with exercise to stimulte
the production of nitric oxide.
Since March 2009, I have been substituting 6 x 200 mg/day Solaray Astragalus Root Extract, that is, 1200 mg/day Solaray
Astragalus Root Extract, to replace GAIA Astragalus Root Extract, which changed in its composition to a weaker
formula I computed to be 1/13th its former strength. Although this is a higher dose than Solaray recommends,
it satisfies my toxicology checks and in initial calculations made the 5 mg/day astragaloside dose that I am experimenting
with available. Note that this requires 3 bottles of Solaray Astragalus Root Extract per month, six 200 mg capsules
per day, for a cost about the same as formerly paid for GAIA Herbs Astragalus Root Extract. This lasts for
15 days, so that one uses 15 days on, 15 days off. Another alternative is Nature's Way astragalus root
extract, which provides 5 mg of astragalosides in 4 capsules x 250 mg of extract per capsule. These come
economically in 60 capsules per bottle, priced as low as $10 each from Herbal Remedies astragalus. Each capsule
comes with extra astragalus root to promote bioavailability. Since Geron recommended doses of
astragaloside IV from 50 mg to 100 mg for telomerase activation treatment, higher doses than 5 mg astragalosides
may be envisioned, although 5 mg astragalosides per day corresponds to about 33 grams of astragalus root itself,
the maximum dose used in Chinese medicine.

Edited by jamesagreen, 30 March 2009 - 04:08 PM.

TA-65 is probably cycloastragenol, judging from Geron's intellectual property documents.
Cycloastragenol is the common alglycone of the astragalosides and the smallest molecule
telomerase activator in astragalus extract. Astragaloside iv has also been tested by Geron
for telomerase activation, but is prescribed at 50-100 mg/day instead of 5 mg/day.
Also, we need more testing of commercially available astragalus extracts rich in astragalosides
such as GAIA Astragalus Extract, which features 1 mg of astragalosides per 30 drops in their
ethanolic astragalus extract. I have been experimenting since May 2007 with 5 mg/day of
astragalosides from GAIA Astragalus Extracts, with fairly good initial results. Eventually
it may be possible with this approach to largely eliminate senescent cells in the body and
reset gene expression to youthful levels for endogenous antioxidants, elastin, collagen, and
other important compounds. I am careful to eliminate telomerase inhibitors such as melatonin,
curcumin, resveratrol, quercetin, green tea, and vitamin E for two weeks while using 5 mg/day
astragalosides, then I switch back for two weeks to plenty of these supplements. This way,
I can catch any cancer cells during the 2nd two weeks of the cycle, but get the benefit of extra
genetic stability against cancer than comes from eliminating senescent cells by lengthening
telomeres with the astragalosides. As far as I know, nothing else currently on the shelf at the health
food store works as well against cellular senescence as well as astragalus extracts. Other drugs just slow
telomere erosion down. Astragalus extracts lenthen telomeres until the t-loops close at the ends of
the telomere and cells return to the pre-senescent immortal phenotype, eventually resetting gene
expression to youthful levels. I get the impression that the maximum benefit from this sort of thing
is about 9 years backwards in time per year of astrogaloside treatment, until you obtain the immortal
phenotype and seem to hang on looking about 28. That is about what my calculations based on
TA Sciences data show can be done with TA-65. I expect I am getting worse results with simple astragalus
extract, but it does seem to be impacting my hair coloration and be reducing the number of grey hairs by
reviving senescent stem cells. More careful scientific studies of readily available astragalus extracts
are definitely in order, both in vivo and on in vitro cell cultures. Astragalus has great low toxicity properties,
accelerates wound healing, lengthens telomeres, is available in glycerin for direct application to skin,
and has been used for a long time to fight B-cell senescence yielding lymphoma night sweats,
being the first effective cure for night sweats found centuries ago. We need more studies to determine
how well astragalus extracts work against senescence in different kinds of cells, and to determine how
fast we may expect to obtain results. A year of my program costs about $225 in my neighborhood,
but I have not got set up yet to do actual telomere length measurements or telomerase activation studies
in connection with these initial probings. After 2 years, the program costs about $750.00 for two years,
using 3 bottles of Solaray Astragalus Root Extract per month at 6 x 200 mg = 1200 mg of extract
per day to obtain 5 mg of astragalosides per day for the first 15 days of every month. Results
after the first two years of testing are on-line at http://greenwood.s5....alus2years.html .
I might add that Vasa, et.al, determined that NO activation lengthens telomeres in endothelial cells.
Exercise increases nitric oxide synthetase levels greatly, and generates the required NO in presence
of arginine, say from bodybuilder's protein powder. Thus bodybuilding with NO supplements refreshes
the vascular endothelium with telomerase activation effect.

TA-65 is probably cycloastragenol, judging from Geron's intellectual property documents.Cycloastragenol is the common alglycone of the astragalosides and the smallest moleculetelomerase activator in astragalus extract. Astragaloside iv has also been tested by Geronfor telomerase activation, but is prescribed at 50-100 mg/day instead of 5 mg/day.Also, we need more testing of commercially available astragalus extracts rich in astragalosidessuch as GAIA Astragalus Extract, which features 1 mg of astragalosides per 30 drops in theirethanolic astragalus extract. I have been experimenting since May 2007 with 5 mg/day ofastragalosides from GAIA Astragalus Extracts, with fairly good initial results. Eventuallyit may be possible with this approach to largely eliminate senescent cells in the body andreset gene expression to youthful levels for endogenous antioxidants, elastin, collagen, andother important compounds. I am careful to eliminate telomerase inhibitors such as melatonin,curcumin, resveratrol, quercetin, green tea, and vitamin E for two weeks while using 5 mg/dayastragalosides, then I switch back for two weeks to plenty of these supplements. This way,I can catch any cancer cells during the 2nd two weeks of the cycle, but get the benefit of extragenetic stability against cancer than comes from eliminating senescent cells by lengtheningtelomeres with the astragalosides. As far as I know, nothing else currently on the shelf at the healthfood store works as well against cellular senescence as well as astragalus extracts. Other drugs just slowtelomere erosion down. Astragalus extracts lenthen telomeres until the t-loops close at the ends ofthe telomere and cells return to the pre-senescent immortal phenotype, eventually resetting geneexpression to youthful levels. I get the impression that the maximum benefit from this sort of thingis about 9 years backwards in time per year of astrogaloside treatment, until you obtain the immortalphenotype and seem to hang on looking about 28. That is about what my calculations based onTA Sciences data show can be done with TA-65. I expect I am getting worse results with simple astragalusextract (about - 5.2 years/year), but it does seem to be impacting my hair coloration and be reducing the number of grey hairs byreviving senescent stem cells. More careful scientific studies of readily available astragalus extractsare definitely in order, both in vivo and on in vitro cell cultures. Astragalus has great low toxicity properties,accelerates wound healing, lengthens telomeres, is available in glycerin for direct application to skin,and has been used for a long time to fight B-cell senescence yielding lymphoma night sweats,being the first effective cure for night sweats found centuries ago. We need more studies to determinehow well astragalus extracts work against senescence in different kinds of cells, and to determine howfast we may expect to obtain results. A year of my program now costs about $600 in my neighborhood (Nov 30, 2009)but I have not got set up yet to do actual telomere length measurements or telomerase activation studiesin connection with these initial probings.I might add that Vasa, et.al, determined that NO activation lengthens telomeres in endothelial cells.Exercise increases nitric oxide synthetase levels greatly, and generates the required NO in presenceof arginine, say from bodybuilder's protein powder. Thus bodybuilding with NO supplements refreshesthe vascular endothelium with telomerase activation effect. Following the recommendation of NobelistLouis B. Ignarro, I use 5 mg arginine per day with 1 gram of L-citrulline per day with exercise to stimultethe production of nitric oxide. Note that exercise also produces telomerase activator IGF-1 after the conversionof HGH in the liver, especially if one uses HGH secretagogues to elevate HGH levels, such as arginine plusornithine (found in fish), or whey protein, or citicholine.Since March 2009, I have been substituting 6 x 200 mg/day Solaray Astragalus Root Extract, that is, 1200 mg/day SolarayAstragalus Root Extract, to replace GAIA Astragalus Root Extract, which changed in its composition to a weakerformula I computed to be 1/13th its former strength. Although this is a higher dose than Solaray recommends,it satisfies my toxicology checks and in initial calculations made the 5 mg/day astragaloside dose that I am experimentingwith available. Note that this requires 3 bottles of Solaray Astragalus Root Extract per month, six 200 mg capsulesper day, for a cost about the same as formerly paid for GAIA Herbs Astragalus Root Extract. This lasts for15 days, so that one uses 15 days on, 15 days off. Another alternative is Nature's Way astragalus rootextract, which provides 5 mg of astragalosides in 4 capsules x 250 mg of extract per capsule. These comeeconomically in 60 capsules per bottle, priced as low as $10 each from Herbal Remedies astragalus. Each capsulecomes with extra astragalus root to promote bioavailability. Since Geron recommended doses ofastragaloside IV from 50 mg to 100 mg for telomerase activation treatment, higher doses than 5 mg astragalosidesmay be envisioned, although 5 mg astragalosides per day corresponds to about 33 grams of astragalus root itself,the maximum dose used in Chinese medicine. Recently I have been using 6 x 200 mg/day Solaray astragalus rootextract with 5 droppers of Herb Pharm liquid astragalus extract, plus 4-8 x 250 mg of Natural Balance Chitosan to improve bioavailability. For results, see http://greenwood.s5....sformation.html. For theoretical background, see http://greenwood.s5.com/longevity.html.