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Telomerase activation cycles

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#31 niner

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Posted 24 May 2013 - 03:03 AM

DorianGrey, you have a very thoughtful approach. I'll try to add a few considerations. A big thing to think about is the bioavailability of the various substances you're considering. Generally speaking, natural products have lousy bioavailability, because we have had millions of years to evolve ways to get them out of our system. Even if a compound is initially absorbed well, it will probably be attacked by your xenobiotic metabolism. Natural products usually present lots of hydroxyls and other functionality that can be tagged with a sulfate or glucoronidate which pulls the molecule into the aqueous compartment and causes it to be quickly excreted. So you need to know how bioavailable each substance is- How much of the dose ends up in the blood? In addition, you want to know something about the pharmacokinetics- How long does it remain in systemic circulation?

Before you decide that a compound is an inducer or an inhibitor, you need to know what concentration is required to see that effect. If you're looking at an in vitro experiment where a compound is an inducer at 100 micromolar, is it even possible to obtain that concentration in the body? Often the answer is no, at least not without something crazy like a huge intraperitoneal injection.

Another consideration is the type of inhibitor you're dealing with. Does it repress expression of the protein component of the HTERT complex? Does it competitively inhibit the complex after it's formed? How does the constitutively active telomerase in a cancer cell, which is in effect "stuck in the on position", relate to the transiently activated telomerase in a healthy somatic cell? Is it even the same situation? Would the compounds behave the same? Maybe. Maybe not. In fact, probably not, since the cancer cell is most likely a poly-mutant. I suspect that none of the natural product compounds that behave as telomerase inhibitors in vitro have relevance to a healthy cell in vivo. The same bioavailability caveats apply to inducers also apply to purported inhibitors.

Yet another point is the length dependence of telomerase. It apparently is unable to extend telomeres that are longer than a certain critical length, and that length is fairly short. Thus average telomere length would not change much, even if you had a successful inducer strategy. You need to measure the proportion of critically short telomeres, which an inducer should reduce. TeloMe.com has a relatively inexpensive test that will give you a number for this. They are just getting off the ground, and will have sale prices available until May 31.

#32 DorianGrey

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Posted 24 May 2013 - 03:41 AM

Hi Niner,
I want to have my baseline test done with TeloMe, I've founded their IndieGoGo campaign. It's about time to shoot them an email, I haven't received a sample kit yet. I wouldn't invest 600$ in a baseline test but 100-200$ is somehow acceptable, considering I need to do further tests in the future. It would be nice to have the histogram, but average is better than nothing.

If there's a fair chance I can lengthen at least my shortest Telomers at a time when my system is still in a good shape and I probably don't have to worry too much about nascent oncogenes, I think one should go for it.
The investment isn't that huge anymore, even cyclo is now down to 80$ for 30 days and a highly bioavailable silymarin would be $30, phyto-estrogenes maybe 20$. But I won't spent 200$/month on an unproven concept, so the dosing has for sure also a financial component. With my other supplements I consider cost, potential benefit and safety, so megadosing isn't for me.

If I wait another 15-20 years until someone has done enough meaningful long-term studies on the small molecule telomerase inducers it might be a little late to get into the game. At this time, it's a lot of guess work but the TeloMe test is a good biomarker for success. I am still exploring what to expect but this forum has been a great help so far. In the end telomerase lenghtening is only one aspect, but it clearly correlates with the detrimental effects of aging.

#33 HighDesertWizard

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Posted 16 August 2014 - 11:59 AM

This video provides a summary overview of the science of Telomeres and Telomerase, including a discussion of the most recent trial and anecdotal evidence. This is a great video to show friends and family new to these issues.

Thoughts about it?

Edited by wccaguy, 16 August 2014 - 12:02 PM.

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#34 ihatesnow

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Posted 17 August 2014 - 07:56 PM

#35 DorianGrey

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Posted 18 August 2014 - 04:08 PM

I'd recommend not to watch the "Why we age - and how we can stop it" video. Nothing new there, just an awful presentation.Thanks for wasting 10 minutes of my time.

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#36 McK

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Posted 19 December 2014 - 02:39 AM

Loved the Dr. Bartnof video, watched it twice.  Surprise to me was such a restrictive diet like Ornish actually lengthened telomeres!  I would have guessed a higher protein diet would have been better.

  I have taken TA-65 but apparently too low a dose for my age-I took one a day and should have taken 2.  I had more endurance but not so much energy rush, eye doctor was impressed with my positive occular improvements, blood pressure was pretty stable around 117/75 to 80, didnt get sick while on it at all and slept well but combined it with 2 mg melatonin at night.

  Down side:  I immediately gained 5 lbs and when I went off TA-65 after 4 months I had gained 10.  I didnt eat any different, exercise the same, and this 10 lbs I am still trying to get off.  Had no effect on sinus drip which is kind of chronic and due to allergies.  Really bumed about the weight gain, and my friend who has stage 4 cancer took it also and he also said he gained about 20 lbs on it but he needed it--I didnt.

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