In anti-aging blog circles the answer seems to be YES, causing endless discussion of how people who want to take these substances and the telomerase activator astragaloside IV should time their doses so the effect of the expensive telomerase activator is not cancelled out. But what does the actual research say? I decided to spend a few hours having a fresh look at this question. Personally, I have resistance to forgoing the cancer protection and other benefits of resveratrol, curcumin and other phyto substances for days at a time in order to benefit from the astragaloside IV. I decided to focus on published experimental research results, not opinions.
To start with, as far as cancer cells are concerned the answer to the question seems definitely to be YES. Here are a few of the many relevant citations: “Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro(ref),” “Effect of resveratrol on proliferation and telomerase activity of human colon cancer cells in vitro(ref).” “Curcumin inhibits telomerase activity in human cancer cell lines(ref),” “Curcumin-induced apoptosis in human leukemia cell HL-60 is associated with inhibition of telomerase activity(ref), Inhibition of telomerase activity and induction of apoptosis by curcumin in K-562 cells(ref),” “Molecular mechanism of curcumin induced cytotoxicity in human cervical carcinoma cells(ref),” “EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells,” leading to suppression of cell viability and induction of apoptosis(ref).” The tea polyphenols EGCG and EGC repress mRNA expression of human telomerase reverse transcriptase (hTERT) in carcinoma cells(ref).” “Epigenetic and genetic mechanisms contribute to telomerase inhibition by EGCG(ref).”
This is just a starting list of research studies for each of these substances that make two central points: 1. The substance leads to apoptosis in the cancer cell line studied, and 2. The substance down-regulates the expression of telomerase in that cancer cell line. In other words the substance down-regulates the expression of telomerase induced by the cancer itself and leads the cancer to kill itself. Note that these substances do NOT lead to apoptosis in normal cells.
Although the research seems to be sparser for other phyto substances in my anti-aging firewalls regimen that are reputed to inhibit telomerase expression [like ginkgo biloba and ashwagandha (Withania somnifera)], the same two central points seem to apply to them as well.
So, what makes us think these substances down-regulate the expression of telomerase in normal cells? Looking into that question, my first observation is that while there is a great deal of research linking the listed substances to telomerase inhibition in cancer cells, there is very little to no such research on how those substances relate to exogenously activated telomerase in normal cells. A few studies jump out suggesting that these substances may do the opposite: promote telomerase activity at least in progenitor cells. For example: “Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms(ref),” “Immortalization of epithelial progenitor cells mediated by resveratrol(ref), “Ginkgo biloba extract reduces endothelial progenitor-cell senescence through augmentation of telomerase activity(ref).” A review study on cell growth regulation states “In addition, curcumin also exerts indirect control over cell division such as inhibition of telomerase activity. Remarkably, some studies point toward a selective growth-inhibitory effect of curcumin on transformed cell lines compared to nontransformed cell lines(ref).”
The bottom line of my mini-review is that I found:
1. What appears to be many dozens or hundreds of articles that answer YES to the question in terms of experimental results but only for cancer cells,
2. Several statements of YES opinion for normal cells, including opinions from reputable researchers, but without backup experimental evidence.
3. Virtually NO actual experimental research studies that say YES for normal cells. Such may well exist. It is just that I could not find them in the time I set aside for looking. My guess is that the opinions come from assuming that telomerase-inhibiting research on cancer cells applies to normal cells as well.
4. A few experimental studies that definitely say NO for normal progenitor cells. At lease resveratrol and ginko activates telomerase expression in some progenitor cell lines.
My personal answer to the question is “I don’t know because there is no published research on what these substances do in normal cells when combined with a telomerase activator. There seems to be no evidence for answering YES in the case of normal cells and some evidence for answering ‘NO, the opposite is true.’” So I am not going to worry too much about taking resveratrol, curcumin, green tea, etc. the same day I take astragaloside IV. Besides, it all seems to be working. See my recent post How am I doing?
TA sciences’s Paton protocol has Ginkgo biloba in it. Why whould they put a telomerase inhibitor in a telomerase activation regimen? i think there is merit in what you are saying here.
I understand your point, but things don’t necessarily connect up. Originally, TA Sciences offered their subscribers an extensive pack of daily supplements including resveratrol and curcumin. When I brought it to their attention that many researchers thought those and other substances in their supplement pack inhibited the expression of telomerase, citing research, TA Sciences created a whole new formulation which is the current one. Now I am wondering if the alarm I sounded was false. The science base behind TA-65 is Geron, and my impression is that TA Sciences is primarily a marketing entity.
This is really SO very helpful, thanks for making this information available to everyone. I have been searching for a solution to the exact problem for the longest time!
Thanks Hillary. Vince
My favorite Resveratrol product is by Jarrow Formulas called Resveratrol Synergy 200. I get it at http://www.VitaminLab.Net because they have the best prices on it. It contains 200 mg of Resveratrol and 100 mg of Vitamin C, Grape Seed Extract 50 mg (95% polyphenols), Grape Skin Extract 100 mg (30% poyphenols), Green Tea 5:1 Extract 200 mg (45% polyphenolics), and Quercetin 100 mg. Everything you need for an antioxidant!
Hi DEllis
I do not know the supplement. Is the resveratrol pure trans-resveratrol? I disagree that it is “Everything you need for an antioxidant,” however, both because some quantities are very small compared with what is needed (e.g. 100 mg of vitamin C while an old coot like me needs to take 30-40 times that amount daily), and other important antioxidants like co Q-10 and curcumin are missing. And some of the amounts are probably too small to make much of a difference. I end to be very suspicious of “one pill does it all” supplements.
Vince
Howdy. I just ran across this tonight and see that you are still keeping up with this. I’ve only recently been able to get ahold of some of the knotweed 50% transResveratol, as I’ve tried hard to read as much about it as I can. I’ve been taking Ginko Biloba for ages, and drinking Green tea for ages.
Now, from what Nikos said way back, I’m guessing that a telomerase inhibitor turns telomerase off? I know that I’ve only recently been seeing the stuff about the ta-65 and learning info about the dna strands and all as well. I’d like to know whether or not I should stop taking any of this. I’m wanting telomerase activated, but not in what is considered the cancer type cells because I’ve heard that if it is turned on, then dna strands actually start getting longer. I will admit though that the whole combination of atleast the tea, ginko, coq10(soon to be the newest coqh), and ginko does have me feeling pretty grand and energized. So, if you could bring me to a little better understanding of what’s meant by these things and with possibly smaller words, that would be great. I’m familiar with the ones you use, but it really sends my brain for a loop.
All in all, I’d like to know what I can about all of this because it’s all what I was using anyway as I just learned how healthy various things were supposed to be over the years. ; p
Thanks!
Hi Dan
I have to keep up with things since the knowledge base keeps growing and evolving. As a matter of strict policy I cannot give you personal advice here. But I can tell you that I continue to take green tea, resveratrol, ginko,and many other dietary supplements that I have taken for years. I am now taking cycloastragenol as a telomerase activator. But of all the substances I take,this is one where I am relatively unsure of what it actually does. I stand by what I say above in the main post.
Checkout my recent post http://anti-agingfirewalls.com/2010/04/09/telomerase-activators-%e2%80%93-what-do-they-really-do/ When it comes to telomerase activators what we seem to have is fascinating and good underlying theory, extremely effective hype and an almost complete lack of clinical evidence.
Vince
Dear Vince,
It certainly would be convenient if resveratrol and
Ginko Biloba activated telomerase in normal cells.
The resveratrol ref you left checks out immediately,
but the Ginko ref is the same one, and the abstract does
not mention the Ginko biloba telomerase activation to
which you refer. I will continue to check into these
insights until I am satisfied, then probably change
my therapy program so that I am taking resveratrol
all of the time. It is well that you maintain a skeptical
attitude and continue to look into matters carefully
for us.
Hi,
well it is well known that 90% of all cancers express telomerase (hTERT the protein coding sub unit)) however normal somatic cells do not express telomerase at all! Only stem cells express low levels of telomerase in a healthy human body.
We can convert a health cell into a transformed pre-cancerous cell by over expressing telomerase in that cell. I have done this with Breast epithelial cells.
So I dont really think that taking substances which activates telomerase is a very good idea.
However, if we start thinking about telomere health, things change a bit.
A normal cell has a limited lifespan, as it ages the telomeres shortern and the cells eventually go into senescence and die (aging). If you can titrate in just enough telomerase to maintain the telomeres then the cell will not go into senescence and it will stay young. If you express too much telomerase, the telomeres will elongate and a pre-cancerous state may arise. So the balance is critical.
Tel:
It is well it is well known that 90% of all cancers express telomerase (hTERT the protein coding sub unit)) however normal somatic cells do not express telomerase at all! Only stem cells express low levels of telomerase in a healthy human body.
VG that has been the conventional wisdom for many years.&
We can convert a health cell into a transformed pre-cancerous cell by over expressing telomerase in that cell. I have done this with Breast epithelial cells.
VG Possibly true. However the complete transformation involves acticvation/inactivation of a substantial number of other genes as well
So I dont really think that taking substances which activates telomerase is a very good idea.
VG I am not sure what the literature says about this, whether there is any research that showed telomerase activation actually leading to cancers. I have not seen any although I have often heard the concern expressed. And as I have discussed in several blog entries including this one, certain research studies say that many innocent substances like resveratrol and vitamin C mildly activate telomerase. Cancers use quite different mechanisms to activate telomerase.
However, if we start thinking about telomere health, things change a bit. A normal cell has a limited lifespan, as it ages the telomeres shortern and the cells eventually go into senescence and die (aging). If you can titrate in just enough telomerase to maintain the telomeres then the cell will not go into senescence and it will stay young.
VG That was my thinking for many years. However there now seems to be a body of research and thinking out there that says the process of cell senescence is very complicated and that shortened telomeres is just one aspect of senescence, a downstream consequence instead of a driver. On the other hand the recent “age reversal” mouse experiment suggests that restoring telomerase expression can restore relative youth though not extemd normal aging. I think the important factor to focus on is telomerase expression rather than absolute telomere lengths as long as they are not critically short. Telomerase does a lot more than extending telomeres.
If you express too much telomerase, the telomeres will elongate and a pre-cancerous state may arise. So the balance is critical.
VG Possibly, possibly not. Many factors regulate telomere length homeostasis in addition to telomerase expression. And I don’t fully buy the pre-cancerous state argument. Have you seen the part of my treatise that deals with the telomere shortening theory of aging? At http://www.vincegiuliano.name/Antiagingfirewalls.htm#Telomereshorteningtheory. And I have written a number of additional blog entries relevant to the topic.
Vince
Resveratrol is a plant extract which are used in more than many ways for health purposes. It was recently featured on the 60 minutes show segment in the ShopNBC. Resveratrol is actually a grape extract and good to know that it helps the vitalization of the health. Normally people like to drink wine and certainly the Resveratrol is one of the ingredients on red wine. Resveratrol is extracted from the grape skin.
Brilliant article. I am struggling with this one too…taking telomerase enhancers as well as EGCG and Curcuma longa. It’s very frustrating and I came upon this fascinating and well researched post during my research today. You can bet this blog will be a favourite of mine from now on. Thank you again for sharing your knowledge, concerns, and confusion!
Hey Rosina de maltby
Welcome to this blog! And thanks.
Vince
I was finally able to confirm that Ginkgo Biloba
activates telomerase in endothelial progenitor cells.
See
http://greenwdks.fortunecity.com/lifexnotes3b3.html#GINKGOBILOBA.
JIM Green
Is the citation you are concerned with at http://www.ncbi.nlm.nih.gov/pubmed/17312453 ? Thanks for tracking thus down. It was the reference I had intented to point to in the blog entry. Not only does Ginko Biloba activate telomerase according to the work cited, but also EPC progenitor cell senescence is delayed. The really interesting question of course is whether the same effect happens in-vivo at the usual doses of Ginko Biloba supplementation. I strongly suspect that nobody has looked at this. I do regularly take Ginlo supplements, however, and they are in my firewalls regimen along with resveratrol of course.
Vince
Think about the underlying physical mechanisms involved: somatic vs cancer.
The mechanism that activates telomerase in healthy somatic cells is well-defined and well-understood. There’s a repressor protein bound to a regulator element controlling the expression of hTERT. You introduce a small molecule that attaches to the repressor protein and this dislodges it from its DNA binding site. The hTERT gene then starts expressing the protein component of telomerase which combines with plenty of available RNA component to form the telomerase enzyme.
Botanicals like curcumin, green tea, boswellia, resveratrol, etc. only cause a problem in somatic cells if they somehow prevent the small molecule in question from coaxing the repressor protein off its binding site. (A good screen finds the small molecules that coax the repressor protein off the DNA, and simulatneously weeds out the molecules that encourage it to hang on tighter.)
In contrast, the mechanisms that activate telomerase in cancer cells are poorly-defined and poorly-understood. There’s no one mechanism. Cancer cells have figured out a plethora of diiferent ways to do it, and no one is close to understanding how many ways there really are — let alone how each individual mechanism works. For example, some cancer cells seem to replicate the telomerase gene over and over again, making many different copies. Others rely on a virus to insert itself upstream of the promoter. The list goes on and on. It varies greatly from one cancer cell line to another.
Suppose you expose some cancer cell line to some random molecule (say curcumin, green tea, boswellia, etc), and then discover via a TRAP assay that telomerase expression has been reduced. What can you then conclude about healthy somatic cells? Very little. There’s a whole series of intermediate mechanisms that occur in the cancer cell in between exposure to the compound and the reduction of telomerase, which the experiment tells you nothing about — and which, as I said, are very poorly understood to begin with. All of this has very little to do with whether or not this particular molecule (curcumin, green tea, boswellia, resveratrol, etc) will make it harder to coax the repressor protein off its binding site in a healthy somatic cell.
In summary, my view is that studies that show reduced telomerase expression in cancer cells lines have little to no relevance in deciding which supplements to take along with a telomerase activator.
I’d like to add that Bill Andrews has addressed this question in a publicly available June 2011 interview.
You can find the transcript and audio of that interview here:
http://100isnew50.com/?sta1
(You must enter a name and email to view it.)
I will quote directly from the transcript:
Q: “Hi Bill, are there any supplements that you recommend not taking because you’ve discovered that they actually reduce telomerase expression in your lab screens?”
A: “There are none that I know of that aren’t safe. Of course you don’t want to take gasoline or something like that. There’s been a few publications suggesting that there are supplements that can interfere with telomerase activity. We have checked every one of them in our labs here, and we have not been able to find that any of them have any significant effect on telomerase activity.”
In my opinion, it’s very foolish to avoid taking these compounds if you’re also taking a telomerase activator. They have very strong anti-cancer properties. The question of whether or not telomerase activation increases/decreases the risk for cancer is still very much being debated. I’ve seen some crazy ideas advocated: for example, that foods rich in dietary polyphenols should be restricted because they inhibit telomerase. This is nonsense.
The fact that compounds like curcumin, resveratrol, EGCG, etc. inhibit telomerase in cancer cell lines simply reinforces the fact that they have strong antineoplastic activity, and likely prevent cancer through telomerase mechanisms and well as many other mechanisms. It has very little bearing on whether these same compounds have any effect whatsoever on the repressor protein in healthy somatic cells. In fact, I strongly suspect that several botanicals that inhibit telomerase in cancer cells do in fact bind to the repressor protein and activate the protein component of hTERT in somatic cells — thus simultaneosly inhibiting telomerase in cancer cells and activating it in somatic cells. Several such compounds are likely in Product B.
I’ve been dabbling with Trans-Reserervatrol for years, plus GH3, but only just getting into and recently purchased Astragaloside IV (98%), Cycloastrogenol (98%), AT-90 (from RevGenetics), plus I bought bulk Astralagus root powder and Astralagus root extract from iHerb.
Since I was getting free postage (to Australia) from iHerb, I also ordered 10 bottles of Gota Kola extract, as I’ve seen amazing results when the sap from the stalk was dabbed daily onto a skin cancer (it grows wild up north, and in SE Asia). I have a bush-herb friend who’s been telling me about it for ten years, long before it was picked up by the pharmaceutical companies and hailed on TV as the latest discovery to fight skin cancer. Whatever it was, the girl had had it on her face for a long time, and after two weeks with the Gota Kola it was gone. My friend also told me a few leaves evrey day is excellent at keeping dementia at bay.
This is the first I’ve heard of the possible conflict, though it’s in a few forums, and the information varies dramatically and lacks citation; I’ll have to do some more research. I’m not a scientist, so I’ll have to read as many posts on the subject as I can, maybe I should alternate months with the Trans-Reserveratrol then the Astragaloside IV (98%), Cycloastrogenol (98%) and AT-90.
I also bought 6 bottles of liquid Syn-RG which is a telemerase enhancer, though not based on any of the abovementioned herbs.
Most peculiar, though, is I bought 5 bottles of Bio Span+, from BioTiva. It’s sold as a supreme all-round longevity supplement, and yet the ingredients (listed as daily intake from 2 capsules) are Trans-Resveratrol 75% 200mg, Silymarin 200mg, Astragalus 300mg, and Curcumin 300mg. All in the one product.
I hope they know what they’re doing. They seem to have a lot of scientific data, test results etc on their site. They use a lot more ingredients than red wine skin to get their Trans-Reserveratrol – complete ingredient list is quite astonishing:
Resveratrol
Pterostilbenes
Polydatin
Polyphenols
Apple Skin Extract
Goji Berry Extract
Pomegranate Extract
Mangosteen Extract
Grape Seed Extract
Alpha Lipoic
Silymarin
Astragalus
Curcumin
Shikimic Acid
Black Elderberry Extract
Pure Star Anise Powder
Eleuthero, Also known as Siberian Ginseng
Fucoxanthin
Garcinia cambogia
Gymnema sylvestre
Chromium
Blueberries
Organic Green Tea
Acai
Vitimin C
Vitimin E
Swiss Alpine plant cells
Peptides
Ferulic Acid
Acetyl Hexapeptide 8
Picied
Polydatin
Pingback: A simple, comprehensive plan to prevent or reverse Alzheimer’s Disease and other neurodegenerative diseases – Part 1: The Plan | AGING SCIENCES – Anti-Aging Firewalls