2189 replies to this topic

[waldemar]

So the optimum mix would be Astragalus, Chitosan and Vitamin C? Interesting. What dosages would you recommend?


sry if this is slightly offtopic...
100YearsToGo: I'd translate "Beweis" as "proof", and not as evidence. Evidence is more like "Hinweis" or "Indiz".

[100YearsToGo]

So the optimum mix would be Astragalus, Chitosan and Vitamin C? Interesting. What dosages would you recommend?


sry if this is slightly offtopic...
100YearsToGo: I'd translate "Beweis" as "proof", and not as evidence. Evidence is more like "Hinweis" or "Indiz".

Ja? Sheisse! I'm fluent in only 4 languages, german is not one of them. My dutch is excellent, bewijs is also a dutch word while hinweis or indiz don't exist in dutch. I hope you' understand why I picked that word.

Phew that was off topic wasn't it?

To get back on topic. I'm waiting on the second telomere analysis result from Anthony. Too bad other people taking Astragalus don't offer any proof of result other than some supposedly reduction of grey hairs. Hell I see less grey hair every day in the mirror. Then my wife brings me back to reality.

[Anthony_Loera]

The next one is in February 2009.
6 Months after the first one...

Cheers
A

[Anthony_Loera]

FYI:

i think I may have a supplier for Saikosaponin A, Astragaloside IV, I did hear a few people telling me they may be able to provide cycloastregenol, but I will see about that in the next two weeks to confirm this.

I think the Las Vegas trip was quite helpful....

A

[ampaynz1]

Thanks for doing so much work and research. I would definitely buy cycloastragenol and would rather take it then astragaloside iv. Even if it cost say $1500 more for the conversion. The benefit is less side effects and requirement goes down to 5mg from say 30-50mg. Say it cost $3500 now instead of $2000. Well you still come out way ahead and have a superior product. I need to read a journal article telling how to do the conversion to know how efficient it is, but I bet it is at least 70%. I once read a journal abstract that described how some Chinese chemists had done the conversion. I looked for this, but was unable to find this. The patent is missing at least several pages of info needed to duplicate the conversion. I don't have the time now. But by looking at articles about cylcoastragenol and looking at their sources one can quickly find out how to convert to it. article about conversion to cycloastragenol It is not the best article, but should help. The hard part is getting the articles, but a local library should be able to get them for a small copy fee. When I went to University of Louisville I had access to almost every article and do miss that a lot. They had one wall in Kersey Library that was simply books cross referencing articles in chemistry and where to find it.

[silvioster]

This is not connected to the use of Astral Fruit per se, but as a caution to the megadose users.



http://www.ncbi.nlm....pt=AbstractPlus



P.S. the usage is completely different from Astral Fruit and similar products, so quantities and results cannot be compared.

[silvioster]

Another paper with oral administration of a mix of extracts including astragalus (3 units) with other herbs (7 units), showing significant effect on alcohol-induced fatty liver.




http://ci.nii.ac.jp/naid/110003609190/

[Anthony_Loera]

This is not connected to the use of Astral Fruit per se, but as a caution to the megadose users.

http://www.ncbi.nlm....pt=AbstractPlus

P.S. the usage is completely different from Astral Fruit and similar products, so quantities and results cannot be compared.

I will completely agree with you on this one... No mega-dosing is necessary anyway, specially with chitosan for the Astragaloside IV component.

Cheers
A

[waldemar]

This stuff sounds more and more interesting.

Is it really a bad idea to combine it with Resveratrol? Somebody mentioned before that Astragalus _inhibits_ telomerase expression in cancer cells, so...

[Anthony_Loera]

This stuff sounds more and more interesting.

Is it really a bad idea to combine it with Resveratrol? Somebody mentioned before that Astragalus _inhibits_ telomerase expression in cancer cells, so...

Hi waldemar,

currently there are 2 studies that I have looked at. One says that Res can inhibit telomerase, and another says the opposite...

So to prevent any issues, I suggest to take the Astral Fruit and resveratrol at least 3 hours apart. I will be getting confirmation sometime late this month or early next month, on what res is really doing...

For now, take them at least 3 hours or more apart.

thanks
A

[mrak1979]

Does anybody know the validity of the claim that astragalus has a bunch of estrogen mimetics?

[stephen_b]

"'Elixir of youth' drug could fight HIV and ageing". New Scientist article.

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.

StephenB

Edited by stephen_b, 13 November 2008 - 07:33 PM.

[mrkosh1]

Hello Anthony,

I've been reading a lot about Astragaloside recently. I find it FANTASTIC that a common plant extract can potentially lengthen telomeres. I find this fantastic because Astragoloside is just a plant extract and the FDA cannot regulate it! The biggest issue I see is that there is currently no proof that Astragaloside can lengthen telomeres in a living organism. Has you company considered testing your product on mice to see if it can enlongate their telomeres?

If it can be proven that astragoloside can lengthen telomeres in an organism I expect that your business could grow very quickly.

Thank you.

Edited by mrkosh1, 20 November 2008 - 06:46 AM.

[ampaynz1]

I believe his own personal results on telomere length will be coming out in very late Feb 2009. His own results are at http://revgenetics.c...thony_Loera.pdf . I like that all his stuff is tested by HPLC. I got a bag of 100grams minus what I took and gave away to friends. I have some doubts it is real because of all the side effects it gave me. Cost to have it tested is $250. I was quoted this price by a chemical company. Will need to do so in the future. Normally, in the USA the chemical supplier will test it and that is more than good enough. As they could literally get sued for lying in USA, but since this herb comes from foreign soil it needs double tested, which revgenetics does.

[Quattro64]

Interesting Topic,

I wonder has anyone tried using Glisodin with Astral Fruit? There are a lot of people here who are taking resveratrol, wondering if anyone knows if glisodin would affect telomerase the same way. I have been taking Glisodin for years and I like what it has done for me but would love to try astral fruit. Glisodin is just a bioavailable form of SOD that seems to really affect how the cell handles free radicals and protects the mitochondria from damage. Seems the two theories of aging currently are the mitochondrial theory of aging and the telomere theory of aging, seems like the two supplements would be complimentary in helping to tackle both theories of aging. Resveratrol also protects the mitochondria in theory, I never started taking it as I saw a while back that it had issues with being bioavailable. Could any of you experts comment on the differences between SOD and Resveratrol?

thanks,

Q

[Anthony_Loera]

Hi Q,

welcome to the forum. Astral Fruit was recently introduced, and I have to say that it may take some time before tests (at least my tests) are completed regarding how it may be helping my telomeres.

I believe I was talking to VinceG (here on this board) the other day, and he mentioned how aging theories are starting to point to certain protective activation of genes, along with telomerase for an increase in possible cell division and organism longevity. This is the exact path we are taking at RevGenetics.

We have recently did an interview explaining part of this strategy a week or so before VinceG mentioned it. If you get "WealthTV" with your local cable , you may see the interview soon in it's entirety with myself and our scientist and telomerase expert Dr. V. (who was trained by Geron while in UCLA).

I expect many competitors to popup after the interview is aired touting similar strategies. We actually don't mind if they do, I believe the purpose of it will allow a large variety of people to benefit from this new direction in supplement considerations for longevity.

Dr V, recently mentioned a 4th gene he would like to target that I haven't mentioned on the board yet. Since I have basically have had an open conversation here about the other 3 genes, I will keep this last one under my hat until a time such as that we can release a formulation for it, and have a funny name for it.

:D

Cheers
A

Edited by Anthony_Loera, 26 November 2008 - 04:02 AM.

[Quattro64]

Thanks Anthony,

I will definetly be buying your AF product soon, I am currently not sure how much to take, how much of a rest period to plan, it seems that with chitosan your product will be very potent, even more potent that TA-65. I do believe that there is evidence that TA-65 is effective at increasing telomere length in vivo, I forgot where I read that? But I did read it somewhere recently. So I have little doubt about your product, I applaud your efforts.

My real question besides potency and amounts to take-rest above, is what to take to help address the mitochondria aging issue. I do think that attacking both theories of aging will help in a huge way with actually looking and feeling younger. I think either Resveratrol or SOD are critical, and it seems after some more googling that both positively affect p53. Maybe it is ok to take both? maybe they both adversely affect Astral fruit? maybe neither do? I think since I have already been positivly affecting my cells by taking glisodin all this time I will cut back to only taking it during rest periods going forward. I will possibly look into taking resveratrol with it. I will be buying your astral fruit and taking it with chitosan, probably 100mgs of chitosan. Two weeks on one week off. I am afraid of your Astral Fruit becoming less effective the longer one takes it as its so potent with chitin, the law of decreasing marginal returns, that is why the rest period, am I making sense?

I've been waiting for a product like yours for a long time, I've been following telomerase since they found it in fruit flys(or was it worms), or mice, linked it to aging and thought it could take a decade to find in humans, a month or two later they found the human variety. Geron came on my radar about then. Very exciting times!

[Quattro64]

I don't get wealthtv but I will be looking for it on youtube. So how does p16 fit into this, do you think it is part of the mitochondrial aging theory, i.e. is it a good candidate for our strategy of protecting our mitochondrial DNA? And there is a forth gene? Cool.

[Anthony_Loera]

There are a large amount of genes, we are just looking at a 4th one that appears to be unique or a 'master' gene much like the other 3.

A

[sethian1]

[quote name='Anthony_Loera' date='25-Nov 2008, 10:56 PM' post='279915']

We have recently did an interview explaining part of this strategy a week or so before VinceG mentioned it. If you get "WealthTV" with your local cable , you may see the interview soon in it's entirety with myself and our scientist and telomerase expert Dr. V. (who was trained by Geron while in UCLA).

Anthony, Why don't you put the video interview on your website?

Bob

[Anthony_Loera]

We can't air the whole interview, we may do some bits an pieces on our site.

I believe at this time, It's also still being edited.

Cheers
A

[geddarkstorm]

This is all wonderfully cool stuff. First you have resveratrol which affects sirtuin function, and answers two of the three faucets of the aging problem (it is now believed that aging accumulates more DNA damage which pulls Sirt1 away from its job in regulating heterochromatin and certain gene expressions like PGC-1, and that this damage induced Sirt1 drain triggers many aspects of aging; and that mitochondria dysfunction is the source of this damage, which res may also prevent), then you have this, which addresses the final part of the aging issue which is telomere loss (we'll find out how well it really does by February, hopefully ).

Talking about tumorgenesis, we see a lot of talk about regulation of p53 and p16 and then confusion about why you can downregulate them and still have strong anti-cancer properties - well that's because p53 and p16 by themselves are only a fraction of the issue and alone cannot stop cancer. Now, everyone may look at me funny, but let's take a look at quercetin to see what I mean. Quercetin is a powerful anti-cancer agent, capable of wiping out cancer cells while leaving healthy cells untouched at doses around 20-100 micromolar. However, it doesn't do this through p53, p16, or telomerase. Instead, quercetin's anti-cancer action comes from three effects: downregulation of MAPK pathways, in which the vast majority of oncogenes are found, and through which the majority of cells turned cancer gain their cancerous properties; downregulation of survivin, which can override the p53/p16 and other apoptotic pathways and stop cell death, and is part of the reason you can have cancer cells that fully express tumor-suppressent genes yet form tumors just fine; and finally upregulation of caspases, which are the effector proteases that start and carry out the apoptotic pathway. Downregulation of caspases by cancer, and upregulation of survivin, means that no matter how much turmor-suppressor genes try, the cell will not die.

Apoptotic and cell survival signals are constantly vying against eachother for an outcome. If a cell lives or dies is determined by the ratio of cell death to cell survival signals. Cancers can either knock down cell death signals (p53/p16/caspases/etc) or upregulate cell survival signals (MAPK, survivin), and many cancers do both, which is why they are so hard to kill in practice though it sounds so easy in theory, and why most chemotherapies and radiotherapies center around literally poisoning yourself and hoping the fast growing cancer cells die first.

The point of this, and how it relates to astral fruit, is that we don't need to keep throwing more and more supplements at our cells to try to regulate these genes. Resveratrol, astral fruit, quercetin, and methylene blue are all a person could need at the cellular level, I think, as they cover all the bases, target both sides of the equations, and basically tell and allow cells to be healthy while wiping out any cell that starts misbehaving. Trying to turn on too many tumor suppressor genes however could have a disastrous effect, such as overwhelming the survival signals and leading to premature cell deaths in the face of normal, repairable DNA damage. We are constantly taking DNA damage, and we only want to kill a cell that screws up as it goes through the cell cycle check points, not every cell that gets damaged, by making sure the ratio of death to survival signals stays sensitive and responsive. P53 and p16 and other tumor suppressors do their job by halting the cell cycle till DNA damage is repaired; but if there is an over abundance of p53 and p16 signaling, you'll go straight into apoptosis without letting repair pathways run their course (otherwise, apoptosis only happens if the cell stalls long enough due to repair pathways failing). If astral fruit and resveratrol are anti-cancer yet do this by upregulating telomerase and and downregulating p53, then there's a reason the body down regulates p53/p16 when telomerase goes up. Trying to force p53/p16 to go up too, is dangerous.

Now this is all theory. We don't have studies that do both: increase telomerase and p53/p16. And all I'm doing is urging caution, that's all, since we're already turning on possibly unknown anti-cancer pathways along with or through telomerase. It's wise, in my opinion, to instead target the survival pathways for downregulation, and increase the amount of apoptotic effector caspases so that cells stay sensitized to the death signal, rather than increasing the death signal. As, invariably, it is loss of sensitivity to apoptosis that causes damaged/abnormal cells to immortalize, and then activation of MAPK pathways (usually) that causes cancer (not all tumors are malignant, after all, and immortal cells can be completely benign, as long as MAPK and other proliferation signals stay off).

Another reason to be cautious with over-regulating p53/p16 is you might cause the very desensitization of the cell to p53/p16 that starts cancer. Desensitization is a very important part of cellular adaptation and happens from processes as diverse as toll-like receptor signaling to type 2 diabetes. The mechanisms of desensitization can be diverse, even when causing the same end result. Genetically engineering in more p53/p16 is different than upregulating p53/p16, and upregulation is what cells have plenty of sensors to monitor and reverse if it gets out of hand. Not every gene is watched the same, and a cell may not be able to desensitize to p53/p16, however it's likely cells can since they make inhibitors to p53/p16. Increase p53/16 levels too much for too long, and the cell may well compensate with more inhibitor, and as soon as you stop using the compound that enhanced p53/p16, or if the cell learns how to ignore it, their levels will plummet and due to the overabundance now of inhibitor you could be left with no functional p53/p16 for a time. See how this can be a problem? All in theory of course. Desensitization is a biological phenomanon that is not nearly given enough thought or study - and then people wonder why drugs stop working or don't work as they thought. It's another reason why we must not mega-dose on any of these factors either. A little upregulation can have amazing beneficial results without causing desensitization it seems, and there are ways to resensitize a cell, like quercetin does with the apoptotic pathways.

So, anyways, this is just my thoughts on all this, my opinions, and so only meant to be taken as such. I can't, nor can anyone, speak with absolute authority on these matters, and I could be wrong on many points. Although my area of study and research is on cellular sensors (MTF-1 to be exact), there are far more mysteries in biology than answers yet, and far too much information for one person to know all the specifics of everything. I just feel that focusing on a few specific compounds that go after completely different pathways, which may still overlap in their end results, but are molecularly completely distinct, like resveratrol and astral fruit do, is the best way to go. Res, astral, querc, potentially methylene blue, they have all the bases covered, so going beyond them and hitting things one too many times may cause trouble. Anything we get in food is likely low enough it doesn't matter, I'm just talking about the huge doses in supplements - even vitamins taken in supplements over long periods of time have been shown in the latest round of studies to significantly decrease life span by increase mortality in the face of disease and injury, and possibly for very similar reasons.

Edited by geddarkstorm, 01 December 2008 - 08:33 PM.

[kai73]

The point of this, and how it relates to astral fruit, is that we don't need to keep throwing more and more supplements at our cells to try to regulate these genes. Resveratrol, astral fruit, quercetin, and methylene blue are all a person could need at the cellular level, I think, as they cover all the bases, target both sides of the equations, and basically tell and allow cells to be healthy while wiping out any cell that starts misbehaving.

could you provide a link to any in vivo study on healthy humans where Resveratrol, astral fruit, quercetin, and methylene blue do any of the things you say?
the truth is that there is no scientific proof...unfortunately :(

Edited by kai73, 01 December 2008 - 11:27 PM.

[geddarkstorm]

The point of this, and how it relates to astral fruit, is that we don't need to keep throwing more and more supplements at our cells to try to regulate these genes. Resveratrol, astral fruit, quercetin, and methylene blue are all a person could need at the cellular level, I think, as they cover all the bases, target both sides of the equations, and basically tell and allow cells to be healthy while wiping out any cell that starts misbehaving.

could you provide a link to any in vivo study on healthy humans where Resveratrol, astral fruit, quercetin, and methylene blue do any of the things you say?
the truth is that there is no scientific proof...unfortunately :(

That's why I said "I think", based on in vitro and animal studies , of which there are plenty of papers to show. All that I listed above have been shown in animal studies to some extent, in mice too. Actually, just do a pubmed.org search for any of those compounds with [title] at the end of the search string, and you'll get a lot of info. I don't know of any studies looking at them all at once, but they do seperate pathways, and I'm hesitant at putting too much into one's system, especially if things hit the same pathways more than once, which was the point of my post.

EDIT: The problem with being on the frontier of science, is it takes science a little while to catch up. So, to answer your challenge, here are four paper reviews (except methylene blue) on other papers dealing with those chemicals including in humans (except methylene blue, see below) so far as has been studied; none are satisfyingly specific, but suggestive and hopeful, and some of the in vitro/animal in vivo effects can be seen in these loose studies in humans (of course, cannot say absolutely that other factors were not playing a role, as these studies are not that specific).

Methylene blue is a special case, it's been used for nearly a century in humans to treat a variety of diseases, and it was only recently that it was discovered that lowering the dose drastically in vitro caused new effects: the delaying of senescence, reversal of mitochondrial dysfunction, and increase of cellular life span. It also inhibits tau protein filaments and is now being looked at as a Alzheimer's treatment.

Astragalus: PMID: 16421421
Quercetin: PMID: 18827577
Resveratrol: PMID: 18537695
Low dose methylene blue in vitro: PMID: 17928358

Put just the number into the pubmed.org search to pull up the paper.

Edited by geddarkstorm, 02 December 2008 - 12:58 AM.

[niner]

Low dose methylene blue in vitro: PMID: 17928358

Interesting. I'd not heard of this before, other than as a treatment for sick tropical fish. I can distinctly remember an entire tank dyed dark blue at my local fish store. ProVepharm has a new process for producing pharmaceutical grade MB. They claim that earlier syntheses used metal catalysts and various heavy metals would always end up in the final product. They didn't say anything about quantities. At any rate, they want to sell the stuff. You could probably buy it at a tropical fish store. It doesn't sound like you need to take all that much. It doesn't kill the fish...

[maxwatt]

Low dose methylene blue in vitro: PMID: 17928358

Interesting. I'd not heard of this before, other than as a treatment for sick tropical fish. I can distinctly remember an entire tank dyed dark blue at my local fish store. ProVepharm has a new process for producing pharmaceutical grade MB. They claim that earlier syntheses used metal catalysts and various heavy metals would always end up in the final product. They didn't say anything about quantities. At any rate, they want to sell the stuff. You could probably buy it at a tropical fish store. It doesn't sound like you need to take all that much. It doesn't kill the fish...

What' the dose? I have some fish medicine.....

About astragaloide, I posted in http://www.imminst.o...&...st&p=281904 that a study hows chitosan enhances absorption.

[Anthony_Loera]

Ok Folks, hold on to your hats....

in about 3 weeks we may know if our next formulation will use Astragaloside IV or Cycloastregenol (According to the CAS number, it appears to be the same herbal saponin from astragalus termed as "TAT2" that Geron used in their press release http://biz.yahoo.com...5497.html?.v=1)...

(Yes, this is part of the reason we haven't released the Chitosan/Astragaloside IV formulation)

Cheers!
A

Edited by Anthony_Loera, 05 December 2008 - 08:48 PM.

[100YearsToGo]

The point of this, and how it relates to astral fruit, is that we don't need to keep throwing more and more supplements at our cells to try to regulate these genes. Resveratrol, astral fruit, quercetin, and methylene blue are all a person could need at the cellular level, I think, as they cover all the bases, target both sides of the equations, and basically tell and allow cells to be healthy while wiping out any cell that starts misbehaving.

could you provide a link to any in vivo study on healthy humans where Resveratrol, astral fruit, quercetin, and methylene blue do any of the things you say?
the truth is that there is no scientific proof...unfortunately :(

That's why I said "I think", based on in vitro and animal studies , of which there are plenty of papers to show. All that I listed above have been shown in animal studies to some extent, in mice too. Actually, just do a pubmed.org search for any of those compounds with [title] at the end of the search string, and you'll get a lot of info. I don't know of any studies looking at them all at once, but they do seperate pathways, and I'm hesitant at putting too much into one's system, especially if things hit the same pathways more than once, which was the point of my post.

EDIT: The problem with being on the frontier of science, is it takes science a little while to catch up. So, to answer your challenge, here are four paper reviews (except methylene blue) on other papers dealing with those chemicals including in humans (except methylene blue, see below) so far as has been studied; none are satisfyingly specific, but suggestive and hopeful, and some of the in vitro/animal in vivo effects can be seen in these loose studies in humans (of course, cannot say absolutely that other factors were not playing a role, as these studies are not that specific).

Methylene blue is a special case, it's been used for nearly a century in humans to treat a variety of diseases, and it was only recently that it was discovered that lowering the dose drastically in vitro caused new effects: the delaying of senescence, reversal of mitochondrial dysfunction, and increase of cellular life span. It also inhibits tau protein filaments and is now being looked at as a Alzheimer's treatment.

Astragalus: PMID: 16421421
Quercetin: PMID: 18827577
Resveratrol: PMID: 18537695
Low dose methylene blue in vitro: PMID: 17928358

Put just the number into the pubmed.org search to pull up the paper.

Niacinamide, dexamethasone and others have also been shown to extend lifespan of human fibroblast in vitro, producing as much as 1.6-fold increase in the number of population doublings . Why take a staining compound with a short track record in life extension properties? Astragalus has not been shown to extend telomeres in humans. Cycloastregenol a stronger compound than Astragaloside IV has only been shown to delay telomere shortening is some immune system cells.

Edited by 100YearsToGo, 06 December 2008 - 02:00 AM.

[geddarkstorm]

Niacinamide, dexamethasone and others have also been shown to extend lifespan of human fibroblast in vitro, producing as much as 1.6-fold increase in the number of population doublings . Why take a staining compound with a short track record in life extension properties? Astragalus has not been shown to extend telomeres in humans. Cycloastregenol a stronger compound than Astragaloside IV has only been shown to delay telomere shortening is some immune system cells.

In my opinion, the difference is the fundamental mode of action. The more specific and direct a mode of action, the better, I feel, unlike with niacinamide and others, which can reek havoc on other pathways (such as downregulation of Sirt1 by niacinamide) that may matter more in vivo than in vitro. That is, we know niacinamide and other metabolic precursors may have several potentially adverse reactions that could become iteratively exacerbated in vivo. This dye, on the other hand, specifically interacts with the mitochondrial electron transport chain when in proportion to cytochrome c levels to give its effects (upregulation of complex IV and ROS defense enzymes, reversal of mitochondrial dysfunction and senescence, not just prolonging life span but also robustness; may also replace oxygen in accepting stray electrons from complexes I and/or III and thus prevent ROS production instead of scavenging, while keeping mitochondrial respiration at its max), and this only occurs at extremely low doses (~100 nano molar, or ~1mg per day), well below the threshold needed for interacting with the other pathways it can target as part of its medicinal use.

That's another difference, that we're dealing with something that's been around and used in humans for nearly a hundred years, and then decreasing the dose, instead of boosting to obscene levels like with niacinamide and others. Boosting doses increases the probability of adverse and unexpected side effects when molecules begin interacting in unexpected ways due to new and favorable thermodynamics caused by overabundance. That is true for all supplements. I believe everything has a U shaped dose response curve, and so proper levels are important.

At any rate, in my view from all the research out there, there seems to be three main modes of aging, which pretty much go in order: mitochondrial dysfunction leads to increased ROS -> increased ROS damage to DNA/proteins decreases Sirt1 regulation of genes resulting in aberrant gene expression in differentiated cells, potentially disrupting function, leading to cancer, and causing many of the phenotypic effects of aging -> telomere shortening in somatic cells leads to chromosomal break down and ultimate life span limit. The four I listed specifically address these issues, which is why they are so interesting to me, at least. After all, for the replication of any species, all for of those issues have to be circumvented in gametogenic cells, so it's possible or there wouldn't be life as we know it.

That is all just my opinion on the matter - and there's certainly no short supply of opinions in the world . Finally, we'll find out more about astragaloside IV here shortly from Anthony in February, with any luck, or maybe even earlier after this 3 week period he speaks of so suspiciously, heh heh. And besides, any controlled telomerase upregulation should be better than none.

[FunkOdyssey]

Niacinamide, dexamethasone and others have also been shown to extend lifespan of human fibroblast in vitro, producing as much as 1.6-fold increase in the number of population doublings . Why take a staining compound with a short track record in life extension properties? Astragalus has not been shown to extend telomeres in humans. Cycloastregenol a stronger compound than Astragaloside IV has only been shown to delay telomere shortening is some immune system cells.

In my opinion, the difference is the fundamental mode of action. The more specific and direct a mode of action, the better, I feel, unlike with niacinamide and others, which can reek havoc on other pathways (such as downregulation of Sirt1 by niacinamide) that may matter more in vivo than in vitro.

Sinclair doesn't think the net effect of niacinamide supplementation is SIRT1 inhibition in vivo:

http://www.alzforum....il.asp?id=1962#

Comment by: David Sinclair (Disclosure)
Submitted 11 November 2008 Posted 11 November 2008

One must be careful when calling nicotinamide an "inhibitor" in this experiment. While it is true that our lab showed that nicotinamide is a direct inhibitor of SIRT1 enzyme, it is also a precursor of NAD+, and NAD+ is a co-substrate (i.e., activator) of SIRT1.

In vivo, there is an abundant enzyme called Nampt in cells and serum that initiates the conversion of nicotinamide to NAD+. Therefore we should entertain the possibility that nicotinamide is activating SIRT1 in vivo, not inhibiting it. This would fit with other papers showing that SIRT1 is neuroprotective.