2189 replies to this topic

[Anthony_Loera]

Hi Tianzi,

Transient rather than permanent telomerase is not the issue. I believe my modified statement zero's in on transient aspect, and stops folks from considering the statement in such a broad way (which turns off alot of folks that have been dealing with permanently turned on telomerase in immortal cells).

The lab you mentioned was done by the company related to Geron and shows the results of 4 types of cancer xenografted on mice. Basically it shows no statistical increase, over regular tumour growth. From the publication below...

If the patient already has cancer, it is likely that the tumor is already telomerase positive, and thus the activator is not likely to impact tumor progression.

This is what the lab results basically show in my humble opinion.

=====================================================

In Telomerase Therapeutics for Degenerative Diseases - Calvin B. Harley*
Geron Corporation, Menlo Park, CA, 94025, USA

Calvin' abstract:

Abstract: Telomerase is active in early embryonic and fetal development but is down-regulated in all
human somatic tissues before birth. Since telomerase is virtually absent or only transiently active in
normal somatic cells throughout postnatal life, telomere length gradually decreases as a function of
age in most human tissues. Although telomerase repression likely evolved as a tumor suppressor
mechanism, a growing body of evidence from epidemiology and genetic studies point to a role of
telomerase repression and short telomeres in a broad spectrum of diseases: (a) Humans with shorter
than average telomere length are at increased risk of dying from heart disease, stroke, or infection;
(b) Patients with Dyskeratosis congenita are born with shortened telomeres due to mutations in
telomerase components, suffer from a variety of proliferative tissue disorders, and typically die early
of bone marrow failure; and © Individuals with long-term chronic stress or infections have accelerated
telomere shortening compared to age-matched counterparts. Telomerase activation may prove useful
in the treatment of diseases associated with telomere loss. While human cells dividing in culture lose
telomeric DNA and undergo changes that mirror certain age- or disease-associated changes in vivo,
telomerase transduced cells have extended replicative capacities, increased resistance to stress,
improved functional activities in vitro and in vivo, and no loss of differentiation capacity or growth
control. In addition, telomerase transduction in vivo can prevent telomere dysfunction and cirrhotic
changes in liver of telomerase knockout mice. Thus, pharmacological activation of telomerase has
significant potential for the treatment of a broad spectrum of chronic or degenerative diseases.

Cells that Respond to Telomerase Gene Transduction with Improved Replicative Capacity, Differentiated
Function, and/or Resistance to Stress

· Bone: Osteoblasts [60-62]
· Brain and the nervous system: Neurons and neural progenitors [49, 63, 64]
· Breast: Mammary epithelial cells [65, 66]
· Connective tissue: Chondrocytes [67]
· Endocrine system: Adrenocortical cells [68]
· Esophagus: Keratinocytes, squamous cells [69, 70]
· Eye: Retinal pigmented epithelial (RPE) cells [71], corneal keratocytes [72]
· Gum tissue: Gingival fibroblasts [73]
· Heart: Cardiomyocytes [45]
· Immune and hematopoietic system (normal): Cytotoxic T cells [74, 75, 15], Hematopoietic stem cells [76]
· Immune system (impaired, e.g. HIV/AIDS): Cytotoxic T cells [16, 77]
· Liver: Hepatocytes [78], stellate cells [79, 80], cholangiocytes [81],
· Muscle: Skeletal myocytes [82]
· Ovary: Surface epithelial cells [83]
· Pancreas: Ductal stem or precursor cells [84]
· Uterus: Endometrial glandular cells [85], stromal cells [86] and myometrial cells [87]
· Skin: Keratinocytes [88], fibroblasts (reviewed in [14], microvascular endothelial cells [89, 90], lymphatic endothelial cells [91, 92],
melanocytes [93]
· Vasculature: Brain [94], retinal [95] and microvascular endothelial cells, smooth muscle cells [96]
· Other: Mesenchymal [61, 97], adipose [98] and bone marrow stromal [99] stem cells; bone marrow endothelial cells [100]

In vivo Models in which Telomerase Activated (hTERT Transduced) Cells have Improved Function over
Control Cells

· Wound healing (human skin reconstitution in mice): Human fibroblasts [43] and keratinocytes (Harley, C.B. unpublished data)
· Neovascularization (normal skin or ischemic hind limb salvage in mice): Human endothelial or endothelial progenitor cells [101, 102]
· Bone formation (human cells or bone fragments injected into mice): Human osteoblasts or mesenchymal stem cells [61, 103]
· Dentin formation (rat cells into rat): Odontoblasts [104]
· Cancer immunotherapy (human melanoma in mice): Human cytotoxic T cells specific for the implanted tumor cells [105]

Potential Uses of a Small Molecule Telomerase Activator:

· AIDS: Improved cytotoxic T cell elimination of HIV-infected CD4 cells
· Cardiovascular and heart diseases: Reduced ischemic damage, improved neo-vascularization
· Chronic ulcers: Improved wound healing
· Joint diseases: Improved cartilage production
· Infections in the elderly: Improved overall immune response
· Liver disease: Improved hepatocyte growth and resistance to stress
· Macular degeneration: Improved RPE cell function; reduced angiogenesis
· Osteoporosis: Improved osteoblast function and bone generation
· Stroke and neurodegenerative diseases: Reduced ischemic damage and increased resistance to neurotoxins (e.g. amyloid)

Last part of publication:

The implications of telomerase activation in the
context of cancer initiation or progression has been
discussed in depth previously [14]. A simplified
approach to this question is illustrated in Fig. (2).
For non-cancer patients suffering from degenerative
disease or chronic conditions caused in part by
telomere-dependent cell senescence, pharmacologic
activation of telomerase should have
relatively rapid benefit. Premalignant cells present
in the patient should also have their telomeres
extended and an extended lifespan could permit
them to acquire additional mutations. However,
most evidence suggests that critically short
telomeres contribute to tumor initiation, and with
immune and other normal cells benefiting from
telomerase activation, it is possible that the net
effect of telomerase activation in such patients
could be tumor suppression. If the patient already
has cancer, it is likely that the tumor is already
telomerase positive, and thus the activator is not
likely to impact tumor progression.

CONCLUSIONS
Telomerase activation is a novel and attractive
approach for the treatment of degenerative diseases
afflicting elderly individuals and those with chronic
conditions or infections that lead to accelerated
cellular aging and loss of tissue homeostasis. The
role of telomerase in conferring increased
resistance to stress expands the potential of a
telomerase activator beyond dividing cells to nondividing
tissues such as heart and brain. Although
telomerase activation is associated with cancer
progression, telomerase is not an oncogene, and in
normal human cells and tissues, controlled
telomerase activation with a small molecule
activator should not impose an unacceptable
cancer risk.

[14] Harley, C.B. (2002) Oncogene, 21, 494-502.

Edited by Anthony_Loera, 08 June 2009 - 01:11 PM.

[VinceG]

Hi all

As a lurker on this site I thought I would check in with an update my personal experience. I started with astragalus extract over two years ago, went onto Astral Fruit shortly after Revgenetics made it available, upped the dose from 33mgs to 66mgs with a chitosan tablet two months ago and increased to 100 mgs (the new formula) a week ago. It is very hard for me to separate out the impacts of the astragaloside IV from that of other substances in my anti-aginmg firewall regimen http://www.vincegiul...BINDEDFIREWALLS.

In general, about to turn 80 in 5 months:
· am experiencing high energy, good health and am feeling good about life.

· My creativity, productivity, ability to think things through and social participation are as high as ever.

· My level of activity including physical exercise remains high.

· In photos, I look about the same age as in ones taken 10-20 years ago.

· I pass my cholesterol, CRP and other annual blood tests and physical exam procedures with flying colors.

· Compared to a year ago I believe my sexual libido is a bit increased, and my eyesight a bit better and keener.

· On the other hand, my hearing has gone a bit downhill.

· There is definitely more grey hair growing on the top of my scalp now. I started balding before 50 and there were hardly any hairs left on top a year ago. At the current rate in another 18 months I will have a full head of hair again, for the first time since I was about 50.

Telomerase activation was one of the big changes in the last year and I think it might largely be responsible for several of the effects including improved eyesight and hair growth. I have also noticed a great deal of skin itchyness since I increased my dose to 100mgs. I do not know if this is due to the astragaloside or to my doing a lot of outside work where there are insects. I mention it because it has been mentioned by others on this blog.

My pattern has been to do a large round of supplements including the ones purported to inhibit telomerase before and right after breakfast and another round just before bedtime, with the astragaloside/chitosan about 5 or 6pm.

Those who follow my blog www.anti-agingfirewalls, know that I see telomerase activation as an important component of an effective anti-aging program but that I see it in a much more nuanced perspective than I originally did. See my updated discussion of this topic at http://www.vincegiul...horteningtheory

Vince

Edited by VinceG, 09 June 2009 - 02:37 AM.

[AgeVivo]

See my updated discussion of this topic at http://www.vincegiul...horteningtheory

impressive web page!

[VinceG]

For Anthony

A question I have had for you for some time. Do I understand you are working on a P16 activator supplement, and if so, why? I fully understand the need to maintain strong apoptotic mechanisms for those doing telomerase activation, but the evidence that P16 causes cell senescence and inhibits the differentiation of somatic stem and progenitor cells and therefore cripples tissue repair and renewal seems overwhelming. The penalty seems to me to far outweigh the benefit. See for example:
<H2 style="MARGIN: auto 0in; BACKGROUND: white">Increasing p16^INK4a expression decreases forebrain progenitors and neurogenesis during ageing
http://www.nature.co...ature05091.html

http://www.nature.co...ature05159.html

p16^INK4a induces an age-dependent decline in islet regenerative potential

http://www.nature.co...ature05092.html

http://cat.inist.fr/...cpsidt=20254708

The list of such literature references implicating P16 in cell senescence and aging goes on and on. In fact, age-related increase of 16(Ink4a) is a major theory of aging that I treat in my treatise. So why in heaven's name would anybody with anti-aging in mind want to promote its expression? Perhaps I am missing something.

Also, I suggest you have a look at this recent post in my blog http://anti-agingfir...ories-of-aging/ where I look at how P16 expression relates to four different theories of aging and cite new research evidence that inhibiting cell senescence via telomerase activation may help limit age-related buildup of P16 which would be a good thing.
Vince
</H2>

[Anthony_Loera]

Hi Vince,

From the study you mentioned (at least the one here "p16INK4a induces an age-dependent decline in islet regenerative potential". Nature 443")

1- The increase of P16 expression tends to reduce the proliferation and division of stem cells, which deals with tissue repair.
2- However, some folks would consider this reduction would essentially help protect against cancer as well.
3- P16 loss (or mutation of P16) is typically seen in 80%-98% of pancreatic cancers
4- But as you pointed out P16 expression tends to make cells vulnerable to cellular senescence...however P16 plays an important part in cell cycle checkpoints, that are used to assess DNA damage. I believe it is used in checkpoint G1 to help determine damage, then notify P53 at that checkpoint while preventing it's degradation.
5- Cellular senescence is good for some folks, and it may be good as well for folks like AgeVivo who are apprehensive about taking a telomerase activator. (I never said the P16 should be taken alone, not cycled, etc) As far as I know, I have only mentioned we are developing it, and have not provided any suggestions on how to take it yet.

P16 has an additional role in cell cycle G1 progression, and is known to be an inhibitor, or tumour inhibitor to prevent the progression of a damaged cell. We know that deleting P16 or P16 mutations allow for some cancers to manifest. Some of these cancers or mutations are normally stopped through the typical cell cycle progression through the help of P16 and others. I believe P16 also helps regulate the cell cycle and keeps P53 from degrading (Mdm2 degradation of P53).

So why a P16 activator? To support proper cell cycle function regarding DNA Damage and repair.
I expect this to be used as needed, not as a permanent daily part of anyone's regimen.

Cheers
A

Edited by Anthony_Loera, 09 June 2009 - 10:21 PM.

[VinceG]

Hi Anthony
Regarding your comments:

1- The increase of P16 expression tends to reduce the proliferation and division of stem cells, which deals with tissue repair.
right
2- However, some folks would consider this reduction would essentially help protect against cancer as well.
right, and can see this point in the case of a precancerous condition, such as Barrett's Syndrome which can lead to deadly cancer of the esophagus.

3- P16 loss (or mutation of P16) is typically seen in 80%-98% of pancreatic cancers
Yes and in other cancers as well. One of the typical transformations to malignancy is to disable P16; another is to turn on expression of telomerase


4- But as you pointed out P16 expression tends to make cells vulnerable to cellular senescence...however P16 plays an important part in cell cycle checkpoints, that are used to assess DNA damage. I believe it is used in checkpoint G1 to help determine damage, then notify P53 at that checkpoint while preventing it's degradation.
Yes again.

5- Cellular senescence is good for some folks, and it may be good as well for folks like AgeVivo who are apprehensive about taking a telomerase activator. (I never said the P16 should be taken alone, not cycled, etc) As far as I know, I have only mentioned we are developing it, and have not provided any suggestions on how to take it yet.

I think for healthy people the issue is balance in theories of what causes aging. Looking primarily at the telomere shortening and the susceptibility to cancer theories alone, sure - activate telomerase and at the same time jack up cancer defenses like P16. If you also consider the theory that says aging may in large part due to decline in differentiation of adult stem cells, you get a completely different answer. That theory says that P16(Ink4a) expression keeps climbing with age and for older folks like me is so high that it is shutting down cell and organ renewal, and that is a major cause of what we observe to be aging. The desirable strategy in this case is to lower the level of P16 while keeping enough around to be a good watchdog against cancer.

P16 has an additional role in cell cycle G1 progression, and is known to be an inhibitor, or tumour inhibitor to prevent the progression of a damaged cell. We know that deleting P16 or P16 mutations allow for some cancers to manifest. Some of these cancers or mutations are normally stopped through the typical cell cycle progression through the help of P16 and others. I believe P16 also helps regulate the cell cycle and keeps P53 from degrading (Mdm2 degradation of P53).
Right again. It is a needed defense

So why a P16 activator? To support proper cell cycle function regarding DNA Damage and repair.
I expect this to be used as needed, not as a permanent daily part of anyone's regimen.

I am glad you made the last point. A P16 activator does not fit in to a daily anti-aging regimen. I am not clear when it would be used however, except as a pharmaceutical intervention in the case of a threatening precancerous condition.

As to cancer protection for those taking Astral Fruit, I made another research pass at the issue and just posted an entry on my blog you might find interesting Do resveratrol, curcumin and EGCG from green tea really inhibit the expression of telomerase? You can find this at http://anti-agingfir...-of-telomerase/

My tentative conclusion is that the experimental research that provides a YES answer to this question is all based on working with telomerase expressed by cancer cells, at least insofar as I was able to divine. There is nothing published I could easily find to support this statement for normal cells. I think it has become a widespread opinion based on assuming cancer cells and normal cells work the same way (they don't). In fact, I am sure you know there are studies that show resveratrol and other phyto-substances as promoting telomerase expression. So I am not worried about taking Astral Fruit and these other substances on the same day.



Take care: Vince

[Anthony_Loera]

Hi VinceG,

a couple things...


First the P16 activator is aimed to be a dietary "cellular cleanse", to help support proper cell division. We are supplement company after all, and sell dietary supplements.
Second, in vitro tests made in California using human blood strongly suggest inhibition using resveratrol... and that is all I can say about that, for now.

Cheers
A

Edited by Anthony_Loera, 11 June 2009 - 10:52 PM.

[unglued]

This abstract from an upcoming conference (that ImmInst is among the sponsors of) touches on some of the points discussed in this topic. It mentions that "several biotech organizations and academic institutions have accepted the challenge of finding ways to prevent telomere shortening by transiently inducing the activity of telomerase" and says that the talk itself will "review the current progress, including the recent discovery of several small molecules that induce telomerase activity in normal human cells." So apparently TA-65 and TAT-2 are not the only ones.

It also states that "anything that is done to extend the lifespan of our cells will also extend the lifespan of our cancer cells". So while the assertion Anthony has repeatedly cited here might yet turn out to be true, it doesn't seem to be an established scientific consensus. (I question the wording of the statement in the abstract, though. My understanding is that cancer cells already express telomerase. The concern is that would-be cancer cells that have had everything go wrong except telomerase activation would become cancerous.)

[Anthony_Loera]

Thanks Unglued,

I am pretty sure there are more molecules that activate telomerase. Which ones are the most potent? That is the main question at this time, It appears Astragaloside IV and Cycloastragenol are the top ones so far, (see page one of this thread).

Cancer cells are already immortal, so I don't understand why the phrase "will also extend the lifespan of our cancer cells" is important, or even there... since they are already immortal.

I think what they were trying to say was that, we can increase lifespan of normal cells, however the organisms lifespan will eventually still be limited by cancer since telomerase does not cure that issue. So we may live longer, but we know that cancer (until a cure is found) is what may eventually kill us. It becomes the main obstacle of longevity.

Well, until Aubrey's work is achieved, then... the sky is the limit.

Cheers
A

[AgeVivo]

I don't understand why the phrase "will also extend the lifespan of our cancer cells" is important, or even there... since they are already immortal.

The theory is that we naturally have many small tumors that do not become life-threatening because their [full or partial] lack of telomerase make them divide a small number of times; if you stimulate their telomerase, transiently or not, you "extend the lifespan" of those small tumors and give them more time to transform them such that they kill you.

Now, theory and reality may or may not match together.

[Anthony_Loera]

Hi AgeVivo,

transiently or not... If cells are damaged and then they try to divide... when the 'new' cells reach G1 (and P16, P53, etc are doing there job, much like those mice that are 'resistant to cancer') the cell goes is either repaired or self destructs. However, in real life I believe that sometimes some genes aren't performing very well at times... and when this happens with certain master genes, whether you increase the damaged cells telomere's or not, you will get cancer.

So if P16 OR P53 (or possibly others) become mutated or not expressed appropriately at G1, you will likely have cancer at some point... no doubt about it. This happens regardless of if you use transient telomerase or are simply living your regular healthy lifestyle...

Again AgeVivo, if you are uncomfortable with transient telomerase, do not take Astral Fruit. However if you want to consider being resistant to the issue, you may want to look at P53, P16 expressions. For myself, I am taking a telomerase activator, I am not uncomfortable with doing so, and I also take resveratrol as stated previously.

For folks like AgeVivo, I simply ask you to wait until there is more data.

For myself, I am convinced there is no increased cancer risk for transient telomerase during my regular lifespan. If I happen to age and become a Super-Centenarian (110+ years in age) with all my faculties intact, and feeling/looking like I am 50-60, then great. I hope by then this thing we call cancer can be dealt with when it decides to show up in my system. If we still don't have a 'cure', then it's ok as having a good quality of life at that age is what most folks want for themselves and their parents.

The goal is to try to extend a good quality of life for as long as possible while adding a decent number of years to life. If you die of an automobile accident, or cancer sometime in those additional years that were granted... is really something our families will have to deal with at that time, all I can say to them when this happens is ...that I tried my best to be around for as long as possible for them.

Cheers
A

Edited by Anthony_Loera, 23 June 2009 - 06:37 PM.

[Anthony_Loera]

Hi Everyone,

We have cycloastragenol now, but we are asking folks who are interested in it, what they would prefer in the Vendor Area:
http://www.imminst.o...showtopic=30937

For folks who are still up in the air or have questions about telomarase, we will continue to talk about the subject here on this thread.

Cheers
A

[niner]

This abstract from an upcoming conference (that ImmInst is among the sponsors of) touches on some of the points discussed in this topic. It mentions that "several biotech organizations and academic institutions have accepted the challenge of finding ways to prevent telomere shortening by transiently inducing the activity of telomerase" and says that the talk itself will "review the current progress, including the recent discovery of several small molecules that induce telomerase activity in normal human cells." So apparently TA-65 and TAT-2 are not the only ones.

It also states that "anything that is done to extend the lifespan of our cells will also extend the lifespan of our cancer cells". So while the assertion Anthony has repeatedly cited here might yet turn out to be true, it doesn't seem to be an established scientific consensus. (I question the wording of the statement in the abstract, though. My understanding is that cancer cells already express telomerase. The concern is that would-be cancer cells that have had everything go wrong except telomerase activation would become cancerous.)

To be honest, I think the author of that abstract is overstating the problem a bit. Because the activation of telomerase by these compounds is transient and as far as we have seen so far, rather mild, I'm not convinced that a cancer cell would not still outrun the ability of transiently active telomerase to keep the telomeres extended. As unglued states, the only cell population that would truly be a concern are those cells for which everything else has already gone wrong, and only the Hayflick limit keeps the cell line from being immortal in addition to experiencing uncontrolled growth. The nub of the question would seem to be the relative speed of tumor cell division versus the rate of extension of telomeres provided by the compounds. If cell division is much faster than telomere extension, then the tumor should burn itself out, although as AgeVivo mentioned above, anything that lets a tumor stay alive a little longer is providing more opportunity for that tumor to acquire a mutation resulting in constitutive activation of telomerase. There are probably people out there who could put reasonable numbers on these relative rates, and help us to know if there is truly a problem. For the time being, my inclination would be to take breaks in telomere activation periodically. I already engage in age-appropriate cancer surveillance; one could always be a little more aggressive with this.

All this raises an interesting question about when we should engage in telomere-lengthening. There is probably not much point in a very young person attempting it at this time. A middle-aged person, on the other hand, might be an ideal candidate in that they would be young enough that having cells with "Everything Broken Except Telomerase" would be unlikely, yet old enough to see a health improvement. Once their telomeres were lengthened, they would be lengthened, so that advantage would stay with them; their telomerase clock would be reset. Of course, by this logic, perhaps a young adult would be an even better candidate! An elderly person would be the most in need of lengthening, but would be the most at risk of already possessing an E.B.E.T. cell population.

Here is the near entirety of the Wikipedia entry on the Hayflick Limit, which is relevant. Note particularly the bolded parts, which mention that 1) Telomerase activation is prevalent in pre-cancerous lesions, thus it's probably not usually the last one to go. 2) Stem cells already express telomerase. To the extent that they are responsible for tumors, the problem may not be so bad. 3) Cancer cells also use the ALT mechanism for telomere extension, so they have another way around the problem anyway.

The Hayflick limit was discovered by Leonard Hayflick in 1965, at the Wistar Institute (Philadelphia), when Hayflick demonstrated that normal human cells in a cell culture divide about 52 times in 20% oxygen (i.e., practically normal air) or 70 times in 3% oxygen (which is the same as human internal conditions). It then enters a senescence phase (refuting the contention by Alexis Carrel that normal cells are immortal). Each mitosis shortens the telomere appendix on the DNA of the cell, thus ticking back an "inner clock" for each subsequent copy of the cell. Some organisms' cells do not encounter the Hayflick limit due to telomere lengthening; for example, the cells of some long-lived sea-birds such as Leach's Petrel are technically immortal.[2]

This telomere lengthening mechanism is believed to have evolved primarily to protect the body from creating a potentially cancerous cell. Because of the fragmented way DNA replicates, a very short telomered cell may lead to genomic instability when the proteins meant to be located on the telomere will fail to attach and the DNA end will be marked as a DNA double-strand break. Telomere shortening together with telomerase activation is one of the most prevalent aberrations in pre-cancerous lesions. [3]

Many stem cells, as they are undifferentiated, are not affected by the Hayflick limit. They exist in every tissue and may continue reproducing for the lifespan of the organism. To avoid reaching the barrier, cells that need to keep on dividing express the telomerase enzyme or use Alternative Lengthening of Telomeres mechanism[clarification needed]. These methods are also used by cancer cells to divide uninhibited.[citation needed]

The normal Hayflick limit of cells in organisms other than humans varies and affects their life span.[citation needed]

Carnosine can increase the Hayflick limit in human fibroblasts,[4] as well as appearing to reduce the telomere shortening rate.[5]

References

1. Hayflick L. (1965). "The limited in vitro lifetime of human diploid cell strains.". Exp. Cell Res. 37 (3): 614–636. doi:10.1016/0014-4827(65)90211-9. PMID 14315085.
2. *Haussmann M. F. et al. (2003): Telomeres shorten more slowly in long-lived birds and mammals than in short-lived ones. Proceedings of the Royal Society of London B: Biological Sciences, 270:1387–1392
3. Scientific article in currented paper: Telomere length, telomeric proteins and genomic instability during the multistep carcinogenic process - http://www.sciencedi...908a79f0dacef15
4. McFarlan GA.; Holliday R. (1994). "Retardation of the senescence of cultured human fibroblasts by carnosine". Exp. Cell Res. 212 (2): 167–175. doi:10.1006/excr.1994.1132. PMID 8187813.
5. Shao L; Li QH, Tan Z (2004). "L-carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts.". Biochem Biophys Res Commun. 324 (2): 931–936. doi:10.1016/j.bbrc.2004.09.136. PMID 15474517.

[sasha59]

Hi,

I've been following this thread for a while and I admit that my knowlege is rather limited, but one impression that I did get was that the effects of astragaloside IV (100mg, used by RevGenetics) and cycloastragenol (5mg, used by TASciences) were the same. Now that RevGenetics has gotten access to cycloastragenol the plan is to sell it for quite a bit more than the astragaloside. Is there in fact a difference in efficacy between the two?

Sasha

[Anthony_Loera]

Hi Sasha,

For most folks the 100mg of Astragaloside IV with Chitosan will remain their product of choice.

From a comparison standpoint:

- Cycloastragenol appears to be more soluble than A4
- Cycloastragenol was the telomerase activator used by UCLA in the study by Effros (see link below)
- We still don't know what TA Sciences uses, we can only assume it maybe Cycloastragenol... but until someone sends me a sample I can't test it to be certain.

I think it will be fair to say that this product is a good step forward, mainly for folks who want a telomerase product that has some sort of study from an unbiased University. For others, it may be an additional item that may support the immune system function to help maintain good health. However because there are no clinical studies (much like resveratrol), no one can make specific claims as to the benefits.

Here is some text on the study:
http://www.natap.org...V/060209_01.htm


Cheers
A

[PWAIN]

Anthony,

Do we know if Chitosan will have any effect on the absorbancy of Cycloastragenol?

How long until a product baed on Cycloastragenol is listed as available? I want to buy some

Wasn't Cycloastragenol listed on one of their patents or research papers?

Hi Sasha,

For most folks the 100mg of Astragaloside IV with Chitosan will remain their product of choice.

From a comparison standpoint:

- Cycloastragenol appears to be more soluble than A4
- Cycloastragenol was the telomerase activator used by UCLA in the study by Effros (see link below)
- We still don't know what TA Sciences uses, we can only assume it maybe Cycloastragenol... but until someone sends me a sample I can't test it to be certain.

I think it will be fair to say that this product is a good step forward, mainly for folks who want a telomerase product that has some sort of study from an unbiased University. For others, it may be an additional item that may support the immune system function to help maintain good health. However because there are no clinical studies (much like resveratrol), no one can make specific claims as to the benefits.

Here is some text on the study:
http://www.natap.org...V/060209_01.htm


Cheers
A

[bdelfin]

Hi,

I've been following this thread for a while and I admit that my knowlege is rather limited, but one impression that I did get was that the effects of astragaloside IV (100mg, used by RevGenetics) and cycloastragenol (5mg, used by TASciences) were the same. Now that RevGenetics has gotten access to cycloastragenol the plan is to sell it for quite a bit more than the astragaloside. Is there in fact a difference in efficacy between the two?

Sasha

I can think of one important difference that doesn't seem to get touched on. Astragaloside IV supposedly doesn't cross the blood-brain barrier, but a few studies have found evidence of highly suggestive effects in the brain, so perhaps a certain amount makes it through. It's molar mass is 784.97 g/mol, which all other things being equal (a dangerous phrase, to be sure) makes it harder for it to cross the BBB. Cycloastragenol, however, has a much lower molar mass, of 490.72 g/mol. It's possible that cycloastragenol travels more easily across the BBB.

Anyone have any data on cycloastragenol's ability to cross the blood-brain barrier?

[Anthony_Loera]

Anthony,

Do we know if Chitosan will have any effect on the absorbancy of Cycloastragenol?

How long until a product based on Cycloastragenol is listed as available? I want to buy some

Wasn't Cycloastragenol listed on one of their patents or research papers?

These are the current patents applied for by Geron's Calvin Harley and the word cycloastragenol:
http://appft.uspto.g...?...LD2=&d=PG01

These are patent applications only at this time, and have not been provided full patent status.

In the United States patents are provided for specific formulations if the item is a natural extract found in a plant (oh, such as Astragalosid IV and Cycloastragenol). If Geron would have made the molecules themselves, and not taken them from an existing plant (like Sirtris did with their SRT1720 formulation), then Geron could have patented the new lab made molecules AND no one in the supplement industry (or TA Sciences for that matter) would be able to provide these for sale.

Having said that, the manufacture or method of extraction for this stuff can also be patented, but not the natural extract itself. If the USPTO considers something a brand new material (like the SRT1720 from Sirtrs), it can be patentable. A4 and Cycloastragenol don't fall into this category, however very specific formulations could be patented.

Cheers
A


P.S. bdelfin - I don't have data on the BBB at this time...

Edited by Anthony_Loera, 02 July 2009 - 03:33 PM.

[tunt01]

interesting new scientific datapoint - Telomerase regulates the Wnt pathway

http://www.eurekaler...c-sdp062909.php

[GreenPower]

Sorry I have made it difficult with the new Astral Fruit.
I didn't know the other company used any carcinogens (Now, that was a surprise to me...).

Well... try this:
Take 1 of our new capsules, open and place powder into a bowl, split it into 3 parts, then mix with a thick liquid that masks the flavor for each part...

The problem is masking the flavor/smell of the stuff.

A

After a three week break in taking AIV (3 x 33mg), I started taking the new 100mg dose with Chitosan today (1 x 100mg). It's pretty strong, but I hope to have grown accustomed to the larger dose in a few days.

After another three months with 1 x 100mg I will take another telomere test and see if there's been any effect.

In either case, I think I will try the Cycloastragenol when it gets available.

Edited by GreenPower, 02 July 2009 - 08:34 PM.

[ampaynz1]

Sasha[/quote]

Anyone have any data on cycloastragenol's ability to cross the blood-brain barrier?
[/quote]

To cross the blood brain barrier the molecule must be lipid soluble. Hydrophilic (polar) molecules can't cross unless they are actively transported via a membrane bound protein carrier channel or are very small. This is how glucose gets across and it is hydrophilic. I have some 98% astragaloside IV and it does not mix well with water at all. It tends to settle after time, but does mix enough at high mixing speeds to make a white solution that is very cloudy with particulates. Astragaloside IV and cycloastragenol are saponins. Saponins are considered amphipathic glycosides. So now what is amphipathic? Amphipathic means the glycoside contains parts that are lipid soluble and parts that are water loving (polar). If you look at the chemical structure of cycloastragenol you will notice a total of four -OH groups. -OH is called the functional group of an alcohol and is very much water loving, thus not lipid soluble at all. Astragaloside IV has 9 -OH groups, which mean it should be more water soluble. If you take a look at the surface area that is completely lipid soluble versus the -OH groups, then cycloastragenol is more lipid soluble. So, yes I do believe cycloastragenol can crosss more easily than astragaloside IV, which may not cross easily. One reason I say this is because morphine can cross and it has two -OH groups. All I have stated is conjecture based on what I've read and will need to proved by some researcher or a chemist here.

[PWAIN]

These are the current patents applied for by Geron's Calvin Harley and the word cycloastragenol:
http://appft.uspto.g...?...LD2=&d=PG01

Thanks for the link Anthony.

I note in the quote below, reference to ginsenosidol. Perhaps this is why ginsen is historically well regarded?

[0079]A "telomerase activator" is a compound that activates or increases the expression or activity of telomerase. A telomerase activator is said to activate or increase the activity of telomerase if the activity of the telomerase in the presence of the compound is greater than that observed in the absence of the compound. Preferably the telomerase is human telomerase. More preferably, the telomerase activator is an astragenol, cycloastragenol, protopanaxatiol or ginsenosidol as described in WO2005/000248, WO2005/044179 and WO2005/000245 all of which are incorporated herein in their entirety

Is this a better method? What method are you using?

[0090]It has surprisingly been found that the level of telomerase activity in hair follicles is easily measured. The level of telomerase activity in hair follicles is relatively higher than in buccal scrapings or peripheral blood mononuclear cells.

[Anthony_Loera]

The Canadian lab uses blood.

I haven't seen a lab that uses hair follicles yet.

Cheers
A

[kilgoretrout]

[ find this whole area pretty far-fetched.
(hmmm... double entendre.. haha! Anti-aging board = "far-fetched"? Oh never mind).

Seems to be an awful lot of energy, talk, and I imagine money being expended about this astragaloside and similar things all based on the silly conviction that if you take a supplement that lengthens your telomeres you could live forever.

Has there been ANY evidence that lengthening telomeres makes anything but (what is they used in the classic studies?) some kind of WORM or maybe a fruit fly live longer?

I think there might be some snake oil salesmen out there (in here???) trying to sell you guys some very expensive and questionable "immortality serum", probably the oldest scam in the book, remember.

Look, WHICH telomeres in WHICH cells in WHICH organs are getting affected by this product? Are there any bonified research studies reporting that using it ACTUALLY RESULTS IN THE LENGTHENING OF ANY LIVE HUMAN'S TELOMERE'S ANYWHERE? I.e., what are the in-vivo results of this stuff? I believe it is: completely nonexistent.

You do not even appear to have any idea if it crosses the blood/brain barrier. Does it penetrate all tissues, all organ systems, EVERY CELL IN THE BODY?

And then there's the fact that cells, even if they have very long telomeres, cells STILL find some way to knock themselves out. Death is a VERY important part of nature's design, and, more to the point, a crucial part of the DNA/RNA-driven evolutionary process (remember "The Selfish Gene"?) and there are no doubt multiple mechanisms to ensure that it happens on schedule. I doubt you are going to defeat it with a pill that works on this one mechanism.

If it DID do something, what is the proper dose and frequency?

And aren't you at all worried that by artificially elevating cells' lifespan, you might be greatly inflating your chances for: CANCER???

I am pretty sure this company and its product are just a sham preying on desperate people obsessed with getting old designed to buy the owners' boats and Caribbean vacations.

And I would hope you have seen this displaimer by the manufacturer saying "we have no idea if this does anything whatsoever"... but they will still take your $40.l00 for 30 worthless pills:

Telomere Effect en Vivo
We want to be clear that there are NO PUBLIC STUDIES supporting the hypothesis that Astragaloside IV activates telomerase. There is only Geron's private work supporting that assertion in vitro. And there are no studies, public or otherwise as to what the effect on shortening telomeres would be like in vivo by Astragaloside IV or by any other telomerase activator. There are anecdotal reports from TA Sciences about TA-65, another telomerase activator, that its use resulted in lengthened telomeres, but no data has been published in that regard.

Do we think that Astragaloside IV would lengthen telomeres in vivo? We don't know. The evidence is not in. If forced to guess, we would say no, because that would just be too good to be true at this early stage. We are hoping instead to slow down the shortening. The type of person that would be a good candidate for this supplement would be an 'early adopter' who is convinced by Geron's work alone that it has enough potential to be worth trying.

[niner]

And then there's the fact that cells, even if they have very long telomeres, cells STILL find some way to knock themselves out. Death is a VERY important part of nature's design, and, more to the point, a crucial part of the DNA/RNA-driven evolutionary process (remember "The Selfish Gene"?) and there are no doubt multiple mechanisms to ensure that it happens on schedule. I doubt you are going to defeat it with a pill that works on this one mechanism.

Although you started out with some good questions, this is a bad argument. No one is saying that we want to suppress apoptosis. That's not what this is about. Or is this a deathist argument?

If it DID do something, what is the proper dose and frequency?

The people in these threads are working on that very question.

And aren't you at all worried that by artificially elevating cells' lifespan, you might be greatly inflating your chances for: CANCER???

You haven't been reading the threads and blogs about this, have you?

I am pretty sure this company and its product are just a sham preying on desperate people obsessed with getting old designed to buy the owners' boats and Caribbean vacations.

And I would hope you have seen this displaimer by the manufacturer saying "we have no idea if this does anything whatsoever"... but they will still take your $40.l00 for 30 worthless pills:

Well, that's just a load. You have no basis whatsoever for either of these claims.

The type of person that would be a good candidate for this supplement would be an 'early adopter' who is convinced by Geron's work alone that it has enough potential to be worth trying.

That would describe the people who are experimenting with this. No one is pushing telomerase activation on anyone.

[Anthony_Loera]

Hi kilgore,

Please read the full thread before commenting or making some pretty silly statements without basis about my company.

Niner has it right on all counts...

Cheers
A

[saxxie]

Hi

Is there any data to suggest that it is better to take the new Astral Fruit capsules with water on an empty stomach or with food? Alternatively should it be taken with something else like olive oil to make it more effective?

SAX

[Anthony_Loera]

Hi

Is there any data to suggest that it is better to take the new Astral Fruit capsules with water on an empty stomach or with food? Alternatively should it be taken with something else like olive oil to make it more effective?

SAX

Hi SAX,

nothing suggests either is preferable, however I tend to lean on taking the supplement alone with water. I believe (correct me if I am wrong folks...) Olive oil inhibits telomerase, so it may not be the best thing to mix it in...

Cheers
A

[saxxie]

Hi SAX,

nothing suggests either is preferable, however I tend to lean on taking the supplement alone with water. I believe (correct me if I am wrong folks...) Olive oil inhibits telomerase, so it may not be the best thing to mix it in...

Cheers
A

thanks!

Check this out: http://www.asianjps.....asp?bsid=14493

sax

[mrak1979]

anthony, olive oil inhibits telomerase? anyone confirm that? Anybody know enything else that inhibits telomerase other than the ones listed in this forum?