75 replies to this topic

[ColonyCitizen079]

Apologies if I'm running afoul some unspeakable forum faux-pas in reviving this thread, but I'm curious about the cost-benefit weighing and risk analysis associated with telomerase inducing as a safe anti-aging method, particularly, if there's any new light here with a way to avoid throwing out the baby with the bathwater with this potentially novel method.

I just read a fairly compelling argument against this approach at Life Extension Magazine in an article back in 2009 debating the safety of telomerase activation--probably not unfamiliar to many of you--titled "Turning on Immortality: The Debate Over Telomerase Activation." In it, ex-Geron corp founder Michael D. West PhD argues convincingly that telomerase induction is risky business, as 90% of cancers rely on it to avoid natural immune suppressors. Somewhat less encouraging was the defense of telomerase basically echoing the same, and ceding that it's a dice roll.

Does anyone know different? If telomerase activation is simply a blind gamble for the more daring, is mitochondrial biogenesis in conjunction with tumor suppression/chemoprevention a more viable aim?

I realize these are very broad terms, and might be given to more conditions and variables than I'm describing, but I'm no biologist, pharmacologist/chemist so pardon my inexperience.

[Telo]

Indeed, a change of paradigm seems to be occurring in telomerase biology, with a switch from viewing telomerase as fueling cancer to reversing aging.

http://www.ncbi.nlm....87/#!po=63.7931


Brian Soto,
I'm one of those dice-rolling people I have been taking cycloastragenol for 18 months and simultaneously also Product B for about half that time. I'm no scientist so what I think may not be important, but the more I read about telomerase and cancer the more convinced I become that taking telomerase activators will probably lower the risk of getting cancer. There are studies showing an association between short telomeres and increasing risk of cancer
http://www.ncbi.nlm....pubmed/20606151 and also, aging is of course a big risk factor for cancer.
Other things that have been found to increase telomerase activity are exercise and meditation and we don't hear any scientist warning people about these things do we?

[Logic]

Info on 2 substances listed by James Green in post #33:
 
Tocotrienol-Rich Fraction Prevents Cell Cycle Arrest and Elongates Telomere Length in Senescent Human Diploid Fibroblasts
http://www.ncbi.nlm....79/?tool=pubmed

More on the above here including sources:
http://www.longecity...ate-telomerase/

GRN510:
A novel telomerase activator suppresses lung damage in a murine model of idiopathic pulmonary fibrosis.
http://www.ncbi.nlm....pubmed/23516479
http://www.geron.com/grn510

 

 

 

 
My own research points decaffeinated green coffee bean extract being a telomerase activator:

"...telomerase-deficient mice have marked metabolic abnormalities owing to downregulated expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and beta (PGC-1α and PGC-1β)..."

"...there seems to be a bidirectional interaction between TERT and Wnt–β-catenin signaling. For example, in mouse embryonic stem cells and Wnt reporter mice, TERT can act as a transcriptional activator of Wnt signaling by complexing with β-catenin (Park et al., 2009). In embryonic stem cells, TERT expression is significantly decreased in the absence of β-catenin, and overexpression of β-catenin increases TERT expression and lengthens telomeres..."
http://dmm.biologist...tent/6/1/9.full

"...Western blot analysis indicated that β-catenin levels were significantly elevated by green coffee bean extract supplementation..."

"...The decaffeinated green coffee bean extract utilized for this study was provided by Naturex Inc. (Avignon, France) under the trade name Svetol. Svetol was obtained by extracting decaffeinated raw green coffee (Coffea canephora robusta) beans with 30% ethanol at 70°C for 2 h..."

http://www.hindawi.c...am/2014/718379/
 
This info was found while looking for info on GRN510.
Note that GRN could possibly stand for: GReeN...?

Edited by Logic, 09 June 2014 - 01:36 PM.

[GreenPower]

I wouldn't say that GRN510 is "novel", exactly. It's been mentioned a few times since the beginning of 2011. It's been some time since I heard anything about it, though. Here the authors give a hint that it's not Cycloastragenol, but it's derived from Cycloastragenol.

 

Cycloastragenol (GRN665 or TAT2) a small molecule isolated from the roots of the plant Astragalus membranaceus (Fig. S1), and activates telomerase in multiple types of human cells in culture including human lymphocytes [21]. GRN510 is a novel and proprietary chemical entity derived from GRN665/TAT2, and is available from Geron Corporation under a Materials Transfer Agreement

[Logic]

Thx Greenpower.

What are your thoughts on my bit of research above on Green Coffee Bean Extract?

Edited by Logic, 14 June 2014 - 09:59 AM.

[GreenPower]

Thx Greenpower.

What are your thoughts on my bit of research above on Green Coffee Bean Extract?

 

Sorry, I haven't read up on the subject. My speculations would probably not add anything of value.

[GreenPower]

Apologies if I'm running afoul some unspeakable forum faux-pas in reviving this thread, but I'm curious about the cost-benefit weighing and risk analysis associated with telomerase inducing as a safe anti-aging method, particularly, if there's any new light here with a way to avoid throwing out the baby with the bathwater with this potentially novel method.

I just read a fairly compelling argument against this approach at Life Extension Magazine in an article back in 2009 debating the safety of telomerase activation--probably not unfamiliar to many of you--titled "Turning on Immortality: The Debate Over Telomerase Activation." In it, ex-Geron corp founder Michael D. West PhD argues convincingly that telomerase induction is risky business, as 90% of cancers rely on it to avoid natural immune suppressors. Somewhat less encouraging was the defense of telomerase basically echoing the same, and ceding that it's a dice roll.

Does anyone know different? If telomerase activation is simply a blind gamble for the more daring, is mitochondrial biogenesis in conjunction with tumor suppression/chemoprevention a more viable aim?

I realize these are very broad terms, and might be given to more conditions and variables than I'm describing, but I'm no biologist, pharmacologist/chemist so pardon my inexperience.

 

I think the usual arguments on safety goes something like this:
1. If you take a temporary activator you will stop extending your cells telomeres when you stop taking it. Cells which divide abnormally fast will then run out of telomeres as usual and stop dividing when they get too short. This mean you will not get cancer unless the cells by themselves have started to upregulate telomerase. The temporary activator by itself won't give you cancer.

2. But some people suspect that cells which have started to divide abnormally fast will have a few extra cell divisions due to the increased telomere lengths gained by the temporary activator. This might increase the risk for a mutation in one of the cells making it start upregulating telomerase by itself. This would then create cancer.

3. Then again, if you manage to rejuvenate your immune system, it will help you fight off cancerous cells.

 

And as Telo mentioned, short telomeres are associated with cancer. My guess is that you probably want the lengths of your cells telomeres to be around 9kb +/- a few thousand base pairs depending on cell type.

[Logic]

HETA-OX
"...High Efficacy Telomerase Activator superior in efficacy to other present agents within telomerase activation capacity and improvement of markers associated with aging..."
http://teamtlr.com/s...61-heta-ox.html

These guys are not saying what this extraxt is, but they are receiving very good reviews here on Longecity:
http://www.longecity...elife-research/

[HighDesertWizard]

I believe this video is a great introduction to and an update on the study status of Telomeres, Telomerase, Diseases, Aging, and Longevity. Toward the end, it includes some very interesting anecdotal accounts related to TA-65 and Telomere Lengthening.

Note to Telomere Category Moderator: I have posted this video in a couple other Telomere threads. I'm not trying to spam the group but believe this video's rich study information content should be seen by more of us interested in the science about Telomeres. It does discuss TA-65 but I think it contains enough general science about the subject to warrant not being relegated to the Product threads.

If there is some single thread that would be a better home for it, I'm happy to have it moved. I didn't want to presume to start a new thread with this video but, perhaps even better than posting it in various threads, this video would be a great first post of a new thread about Telomeres. Perhaps it is the first post in a new thread that is Pinned. I'm happy to do whatever is thought best. People need to see it and if its the first post in a thread and/or in this Category, more people will. 

Enjoy!

Edited by wccaguy, 19 August 2014 - 07:49 PM.

[Logic]

Nuclear Aging: The View from the Telomere end of the Chromosome Part 1 – context, history, and about telomere lengths
http://www.anti-agin...mere-lengths-2/

Nuclear Aging: The View from the Telomere end of the Chromosome – Part 2 – Telomere Molecular Biology
http://www.anti-agin...ecular-biology/

Nuclear Aging: The View from the Telomere end of the Chromosome – Part 3 – Telomere Molecular Biology and GUT implications – The two faces of P53
http://www.anti-agin...o-faces-of-p53/

From the above it is obvious that more expression of SIRT6 and increasing NAD+ levels is good for telomere length, DNA repair, cancer avoidance etc-etc.

Activation of the Protein Deacetylase SIRT6 by Long-chain Fatty Acids and Widespread Deacylation by Mammalian Sirtuins.
"...we demonstrate that several biologically relevant FFAs (including myristic, oleic, and linoleic acids) at physiological concentrations induce up to a 35-fold increase in catalytic efficiency of SIRT6 but not SIRT1..."
https://wp.discovery...ctivation-2.pdf

Rolipram rescues oxidative stress-induced premature phenotypes by SIRT6-dependent NF-kappaB inhibition.
"...Here, we demonstrated that Rolipram, the specific PDE4 inhibitor, could increase cyclic AMP level to rescue the pathophysiology in premature mice. The mice treated with Rolipram showed increased SIRT6 and reduced acetylated NF-kappaB protein level..."
http://www.fasebj.or...plement/1142.11

Icariin intervenes in cardiac inflamm-aging through upregulation of SIRT6 enzyme activity and inhibition of the NF-kappa B pathway.
http://www.google.co...T60T0Sx_gKKKMWg

I hopet his research is better received than that on Green Coffee Bean

[Logic]

Scientists discover an on/off switch for aging cells
The switch controls the growth of telomeres, the timekeepers of cells
http://www.salk.edu/...p?press_id=2052
http://genesdev.cshl...56.114.abstract

[pone11]

Telomerase inducers do not increase mouse lifespan: http://healthactivat...ephen-spindler/

 

I enjoyed that presentation, and it is a stark reminder to all of us to only supplement with things that have strong evidence of dramatic impacts on health.   I have personally done some horrible things to myself with supplements, so his message just reinforces my experience.

 

Here is full text of one of Spindler's studies, for those who want to get a sense of his research:

http://online.lieber...9/rej.2012.1386

[Castiel]

 

 

DL-Alpha Lipoic Acid (134) (Product B, List) lengthens fibroblast telomeres. Antioxidant.

Is that the same as regular alpha lipoic acid or is there something different about the DL portion of the name?

 

 

Alpha lipoic acid was recently shown to also activate telomerase in smooth muscle cells, enough to positively affect diseased states.   

if it stimulates telomerase in smooth muscle cells and also fibroblasts, might it not activate it in other cell types too?  And if it can positively affect disease states in animal models might the activation not be substantial?

Edited by Castiel, 23 August 2015 - 06:05 PM.

[jamesagreen]

Try the list of telomerase activators at http://www.greenray4...LPHABETICSELECT . 

The list was compiled between March 2007 and May 2015. Perhaps this is the best list of telomerase activators

available to the public. The information on the various telomerase activators is online at

http://www.greenray4.../longevity.html . Press TOPICS at http://www.greenray4...vitytopics.html

and look up the various files on telomerase activators. The list of telomerase activators has improved somewhat

since May 2015, and may be available online later on. 

 

The telomerase inducers description of telomerase activators was popularized by Dr. William Andrews, 

who really did quite a few measurements with automated assay technology to find telomerase activators 

that exhibit some activity in dermal fibroblasts. Notes on these telomerase activators are online 

at http://www.greenray4...fexnotes11.html , the Product B explorer. Some of the mechanisms 

behind the telomerase activators have become more clear since May 2015, but there is just a small

volume of improvement since then. 

 

Various telomerase inhibitors are described online in http://www.greenray4...notes3b1.html. 

 

 

 

 

 

[mrkosh1]

Have there been any breakthroughs lately on natural substances -- or unnatural substances that can be easily obtained -- that induce telomerase?

 

My whole view of the anti-aging world has changed in the past year. No longer does telomerase inducing substances seem the be the most promising anti-aging interventions, but NAD+ production and NFR2/NQO1 activation also seems very important. However, finding a supplement that could be taken intermittently that would radically boost the level of telomerase would still be a breakthrough. Interestingly, by increasing the level of NAD+ the SIRTs are activated which then activate PGC1a that proceeds to induce telomerase. There are papers that describe how this can be done with alpha lipoic acid -- although other papers seem to indicate that in some cell types alpha lipoic acid slightly reduces the production of telomerase.

 

 

[PeaceAndProsperity]

Try the list of telomerase activators at http://www.greenray4...LPHABETICSELECT . 

It appears to be your own website. Still an interesting resource. 

Have you achieved yourself any noticeable youthening?