18 replies to this topic

[QQQ]

I wonder if de Grey supplements with Astragalus.





A drug extracted from a plant used in Chinese medicine has helped immune cells fight HIV and raises the possibility of slowing the ageing process in other parts of our bodies.

The method hinges upon telomeres - caps of repetitive DNA found at the ends of chromosomes. These get shorter as cells age and are thought to affect the cell's lifespan.

The caps can be rebuilt with an enzyme called telomerase, and some people have suggested it might be possible to extend human life by boosting telomerase production - though this has never been tested.

Now Rita Effros at the University of California in Los Angeles has used a drug that boosts telomerase to enhance the immune response to viruses.

Effros and her colleagues had previously inserted part of the telomerase gene into so-called killer T-cells - immune cells that fight infections including HIV - and found that the cells had stronger anti-viral activity than normal. However, such gene therapy is not a practical way of treating the millions of people infected with HIV.

In the latest work, Effros took killer T-cells from HIV-infected people and exposed them to TAT2. Developed by Geron Corporation of Menlo Park, California, TAT2 is a drug extracted from the root of a plant called Astragalus that is thought to boost telomerase production and is traditionally used in Chinese medicine as a boost for the immune system.

She found that TAT2 reduced telomere shortening, increased cells' ability to divide, and enhanced their antiviral activity.

This effect was blocked when a second drug was used to inhibit telomerase, suggesting that TAT2 was indeed working through the enzyme - although the exact mechanism is not understood.

<h3 class="crosshead">Immune boost</h3> "It is beginning to look like telomerase is doing more than just keeping telomeres from getting too short," says Effros. "It seems to be mediating some anti-viral mechanisms as well."

Interestingly, a previous study suggested that people with HIV who control the infection for many years without developing AIDS, have killer T-cells with high telomerase activity and longer telomeres.

Ultimately, Effros hopes that TAT2 could be used to supplement existing anti-retroviral drugs, by boosting the immune systems of people with HIV.

Aubrey de Grey of the Methuselah Foundation, which promotes research into lifespan extension, says the study is a big step forward.

"It is what we would have hoped," he says. "We've thought for some time that, by activating telomerase in these cells, we could extend their proliferative capacity. What was completely unclear was whether that would [have negative side effects]. These cells become fully functional as a result of the restoration of their proliferative capacity."

However, some safety concerns remain, as telomerase is known to be produced at higher than normal rates in cancer cells.

<h3 class="crosshead">Low cancer risk</h3> The good news is that when TAT2 was added to tumour cells it didn't affect the amount of telomerase that was produced by the cells. Neither did it change the growth characteristics of immune cells that were incubated with a virus that can trigger cancer.

"We are fairly confident at this point that TAT2 won't enhance cancer development," says Effros, although she cautions that further trials are needed to confirm this.

Her confidence is also boosted by the fact that Astragalus is used in Chinese medicine without any obvious adverse effects. She warns, though, against taking large doses of Astragalus to try and mimic the TAT2 effect. "Uncontrolled use of any herbal drug is not wise and I would not advocate it," she says.

Effros and de Grey believe that TAT2 could also find applications in other diseases and general ageing - though these have not yet been tested. Killer T-cells fight many other viruses besides HIV, and often enter into a state of anergy - where they stop dividing but won't die - in elderly people. Since response to flu vaccine in elderly people seems to be correlated with having lots of killer T-cells with short telomeres, "One can envision perhaps improving the vaccine response and other anti-viral responses in the elderly by TAT2," says Effros.

And in terms of more general tissue regeneration, "if TAT2 can do what the telomerase gene seems to do by keeping cells growing and functioning longer, maybe it could help in tissue regeneration approaches to ageing."

[luv2increase]

Maybe one should supplement with both the non-extracts of Astragalus and Ashwagandha?

[100YearsToGo]

Here is the study:

http://www.jimmunol....act/181/10/7400


Telomerase-Based Pharmacologic Enhancement of Antiviral Function of Human CD8⁺ T Lymphocytes¹
Steven Russell Fauce^*, Beth D. Jamieson, Allison C. Chin<A name=RFN2>^2,, Ronald T. Mitsuyasu, Stan T. Parish^*, Hwee L. Ng, Christina M. Ramirez Kitchen, Otto O. Yang, Calvin B. Harley and Rita B. Effros^{3,* *} Department of Pathology and Laboratory Medicine and Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095; Geron, Menlo Park, CA 94025; and Department of Biostatistics, University of California-Los Angeles, School of Public Health, Los Angeles, CA 90095



Telomerase reverse transcribes telomere DNA onto the ends of linear chromosomes and retards cellular aging. In contrast to most normal somatic cells, which show little or no telomerase activity, immune cells up-regulate telomerase in concert with activation. Nevertheless, during aging and chronic HIV-1 infection, there are high proportions of dysfunctional CD8⁺ CTL with short telomeres, suggesting that telomerase is limiting. The present study shows that exposure of CD8⁺ T lymphocytes from HIV-infected human donors to a small molecule telomerase activator (TAT2) modestly retards telomere shortening, increases proliferative potential, and, importantly, enhances cytokine/chemokine production and antiviral activity. The enhanced antiviral effects were abrogated in the presence of a potent and specific telomerase inhibitor, suggesting that TAT2 acts primarily through telomerase activation. Our study is the first to use a pharmacological telomerase-based approach to enhance immune function, thus directly addressing the telomere loss immunopathologic facet of chronic viral infection.

Edited by 100YearsToGo, 15 November 2008 - 08:35 PM.

[FunkOdyssey]

I predict a run on Astral Fruit in the near future.

[niner]

Yeah, Anthony may have a growth business on his hands. Question: What's the structure of TAT2? How is it related to TA65? To Astragaloside IV?

[Anthony_Loera]

From the paper:

In an empirical screen of traditional Chinese medicine plant extracts and compounds with reported properties of health maintenance and enhancement of immune function, we identified TAT2 (cycloastragenol) based on its ability to up-regulate the low, basal level of telomerase in neonatal human keratinocytes (unpublished data).

A

[saxiephon]

From the paper:

In an empirical screen of traditional Chinese medicine plant extracts and compounds with reported properties of health maintenance and enhancement of immune function, we identified TAT2 (cycloastragenol) based on its ability to up-regulate the low, basal level of telomerase in neonatal human keratinocytes (unpublished data).

A

Hi Anthony,

Are you considering adding cycloastragenol to your Astral Fruit or would the cost be prohibitive?


Thanks, SAX

[100YearsToGo]

For the DIY guys/Girls,

"Conversion of astragaloside IV(1) to cycloastragenol(2)
To astragaloside IV (1) (5.00 g, mmol) was added"HCl-MeOH 10" (TCI
America) (500 mL) and the mixture was stirred at room temperature for
7 days. The reaction mixture was concentrated to about half volume
under reduced pressure at 20 C (do not heat). The mixture was
partitioned into aqueous sodium bicarbonate and ethyl acetate.
The aqueous layer was extracted with ethyl acetate again. The organic
layers were combined, washed with saturated sodium chloride, dried on
anhydrous sodium sulfate, and concentrated under reduced pressure. The
residue was purified by column chromatography (20:1-14 : 1 chloroform/
methanol). In order to replace the residual solvent with ethanol, the
purified material was dissolved in ethanol and the solvent was removed
under reduced pressure to afford 2 (2.1 g, 64%)."

Cycloastragenol could be considered a drug by the FDA. It is a synthesized compound. On the other hand, it is present in miniscule amounts in astralagos, so it could be considered a natural product. Anthony should be carefull.

[100YearsToGo]

For the DIY guys/Girls,

"Conversion of astragaloside IV(1) to cycloastragenol(2)
To astragaloside IV (1) (5.00 g, mmol) was added"HCl-MeOH 10" (TCI
America) (500 mL) and the mixture was stirred at room temperature for
7 days. The reaction mixture was concentrated to about half volume
under reduced pressure at 20 C (do not heat). The mixture was
partitioned into aqueous sodium bicarbonate and ethyl acetate.
The aqueous layer was extracted with ethyl acetate again. The organic
layers were combined, washed with saturated sodium chloride, dried on
anhydrous sodium sulfate, and concentrated under reduced pressure. The
residue was purified by column chromatography (20:1-14 : 1 chloroform/
methanol). In order to replace the residual solvent with ethanol, the
purified material was dissolved in ethanol and the solvent was removed
under reduced pressure to afford 2 (2.1 g, 64%)."

Cycloastragenol could be considered a drug by the FDA. It is a synthesized compound. On the other hand, it is present in miniscule amounts in astralagos, so it could be considered a natural product. Anthony should be carefull.

Well I was waiting for someone else to do it, as I hate posting negative stuff.

Was I the only one to notice that cycloastragenol only modestly retards telomere shortening? That means it does NOT rebuild telomeres. Bummer for old guys. As cycloastragenol can be synthesized from astragaloside IV in a ring closing reaction and is purportedly "stronger" than astragaloside IV I'm starting to wonder if astragaloside IV will do anything at all.

Regards,


100YTG

[stephen_b]

That means it does NOT rebuild telomeres. Bummer for old guys. As cycloastragenol can be synthesized from astragaloside IV in a ring closing reaction and is purportedly "stronger" than astragaloside IV I'm starting to wonder if astragaloside IV will do anything at all.

Regards,


100YTG

I'm hopeful that the 60 fold increase in absorption of astragaloside IV by adding chitosan (PMID 16715776) will make a difference.

StephenB

[OneScrewLoose]

-

Edited by OneScrewLoose, 19 November 2008 - 12:56 AM.

[niner]

Well I was waiting for someone else to do it, as I hate posting negative stuff.

Was I the only one to notice that cycloastragenol only modestly retards telomere shortening? That means it does NOT rebuild telomeres. Bummer for old guys. As cycloastragenol can be synthesized from astragaloside IV in a ring closing reaction and is purportedly "stronger" than astragaloside IV I'm starting to wonder if astragaloside IV will do anything at all.

But didn't TA Sciences present data claiming that at least for some cells in blood, their compound (presumably cycloastragenol) did in fact lengthen telomeres?

[100YearsToGo]

Well I was waiting for someone else to do it, as I hate posting negative stuff.

Was I the only one to notice that cycloastragenol only modestly retards telomere shortening? That means it does NOT rebuild telomeres. Bummer for old guys. As cycloastragenol can be synthesized from astragaloside IV in a ring closing reaction and is purportedly "stronger" than astragaloside IV I'm starting to wonder if astragaloside IV will do anything at all.

But didn't TA Sciences present data claiming that at least for some cells in blood, their compound (presumably cycloastragenol) did in fact lengthen telomeres?

There is no data or study to support that. They only say that it activates telomerase. That does not mean it lengthens telomeres. Activating telomerase on itself may have health benefits. It seems all the TA compounds are the same thing only in different concentrations:

Feel free to browse their docs:

http://www.tasciences.com/docs/

in one of them, a safety study, it says:

" 40 mg. TA-41 daily is essentially equivalent to a daily dose of 5 mg. of TA-65."

The safety study does not show anything spectacular going on either. I'm afraid we can forget telomere lengthening. I'm very sceptical. If they had anything on that, they would have published.

[niner]

Well I was waiting for someone else to do it, as I hate posting negative stuff.

Was I the only one to notice that cycloastragenol only modestly retards telomere shortening? That means it does NOT rebuild telomeres. Bummer for old guys. As cycloastragenol can be synthesized from astragaloside IV in a ring closing reaction and is purportedly "stronger" than astragaloside IV I'm starting to wonder if astragaloside IV will do anything at all.

But didn't TA Sciences present data claiming that at least for some cells in blood, their compound (presumably cycloastragenol) did in fact lengthen telomeres?

There is no data or study to support that. They only say that it activates telomerase. That does not mean it lengthens telomeres. Activating telomerase on itself may have health benefits. It seems all the TA compounds are the same thing only in different concentrations:

Feel free to browse their docs:

http://www.tasciences.com/docs/

in one of them, a safety study, it says:

" 40 mg. TA-41 daily is essentially equivalent to a daily dose of 5 mg. of TA-65."

The safety study does not show anything spectacular going on either. I'm afraid we can forget telomere lengthening. I'm very sceptical. If they had anything on that, they would have published.

I might be remembering something that was said at a conference or some other source that didn't make it into the literature. At any rate, lots of good stuff in the /docs directory, including the paper being discussed here. In the text of the paper, they said:

The TAT2 telomerase enhancement effect on PHA-activated PBMC from healthy adults was relatively modest, ranging from 1.5- to 2.5-fold (Fig. 1c), possibly due to the fact that PBMC from younger, healthy individuals already have high endogenous activation-induced telomerase levels. By contrast, the increased telomerase activity induced by TAT2 in PBMC from persons who were chronically infected with HIV-1 but asymptomatic, or from persons who had progressed to AIDS, was more dramatic, ranging from 2.5- to 7-fold (Fig. 1c). This observation was consistent with the previous demonstration of lower telomerase activity in PBMC from HIV-1-infected donors compared with agematched seronegative controls (25). Indeed, the most dramatic telomerase enhancement by TAT2 was observed in the PBMC that had the lowest levels of endogenous telomerase activity, i.e., from chronically HIV-1-infected and AIDS donors. Similar telomerase enhancement was observed in purified T lymphocytes stimulated with CD2/CD3/ CD28-coated beads, where TAT2 treatment not only increased telomerase activity, but prolonged the period poststimulation during which telomerase was active (Fig. 1d).

Now, these CD8+ T cells are not your typical somatic cell. They apparently have telomerase that is always "on", at least in young healthy cells. The fact that cycloastragenol cranked up the telomerase activity a lot more in cells where it was already "off" (or nearly so) is a pretty good sign. That would suggest that it might work as hoped in more typical cells. In the discussion section of the paper, they did make the following speculation:

We speculate that TAT2 might moderately extend the lifespan of “presenescent cells” with low telomerase activity through modest up-regulation of telomerase and extension of the shortest telomeres in individual cells.

It's not exactly the sort of slam-dunk language I'd like to hear, but it's something.

[Anthony_Loera]

Now that one "Epithalon peptide" may be great for a cream, if folks wanted to go around the "astragaloside iv" and "cycloastreganol" formulation found here:

See Fig 2 in this patent, it shows "astragaloside iv" telomearse activity against a control in Geron's cream formulation:
http://www.google.co.....conditioning"


Of course we are not copying anyone's patent, but we are interested in the studies made public in the patent regarding a naturally occurring saponin found in tiny amounts in Astragalus.

Cheers
A

Edited by Anthony_Loera, 19 November 2008 - 07:38 PM.

[mrkosh1]

I have to read the whole stuff about TAT2 once I have a little bit more time but:

Even if the whole astragaloside/cycloastragenol issue turns out to not be sufficient, we have still epithalon (epitalon).
It activates telomerase, elongates telomeres in human cells and decreases the rate of some cancers in mice. (1,2)
I have seen an excerpt of one paper, where the telomere elongation is shown somewhere at google books.

Actually, we do not have epithalon. The great thing about astragalus is that it's available now because it's an extract from a herb. That means the FDA cannot regulate it. It could be many years before epitalon is approved for human use and probably decades before it's approved for anti-aging purposes.

I think that astragaloside deserves more research.