Bill Andrews announces full telomere extension treatment, clinical trials soon to follow

They've now released Defytimer in capsule form:

 

bhttp://defytimer.com...ement-defytime/

 

Be very skeptical here.

 

Here's a working link to "Bob Seitz is 85-years young and getting younger". http://www.rechargeb...unger/#comments

 

I don't see any difference...

 

I have serious doubts, straight to market with his product?

 

They've now released Defytimer in capsule form:

 

bhttp://defytimer.com...ement-defytime/

 

Be very skeptical here.

 

 

Here's a working link to "Bob Seitz is 85-years young and getting younger". http://www.rechargeb...unger/#comments

 

I don't see any difference...

 

I have serious doubts, straight to market with his product?

 

 

Bob Seitz is or was a LongeCity member:  http://www.longecity...ad/#entry654235

What I think we need is to measure telomeres on something other than the immune system. Skin sounds like an easy place to get it. So far much if not all of the research has focused on immune system tests. A strong immune system in old age might keep the flu from killing you a few extra years, but I think we should be aiming higher. I want to see telomere and DNA methylation testing done on skin cells.

I have been looking at TAM-818 ads and noticed it has a patent application and he mentioned his company made it from available molecule and is a synthetic as a plant has never made it on purpose. It was quite interesting to read several of his patents as it shows how few molecules there are in the cells and the difficulty in detecting telomerase. The molecule below is suspect on being related to TAM-818 as it is the main one in the application and also no chemical company makes this exact molecule and different ones on pubchem are different and toxic, so alteration is necessary. Maybe there is a patent in New Zealand. The patent cited here is application is US20090143451A1  . 

 

5-thiophen-2-yl-isoxazole-3-carboxylic acid propylamide having the following structural formula:

 

 

1. Wow

 

2.I'm thinking that Astragaloside IV and TA65 are both different in their mechanisms and both should be taken. Have you seen any studies testing this? My rationale is that shorter telomeres are going to whip around more because there is less resistance holding them back, this leads to faster activity, so a drug that lengthens critically short telomeres is likely to increase the activity of Telo Reverse Transcriptase, CST-complex proteins, or nonsense mediated decay factors. If Astragaloside IV does not have preference, then it's action is more likely one of activating Shelterin or Terra as doing so would lengthen all telomeres. This may have been the initial reasoning behind deciding to go with TA65 as opposed to using Astragaloside IV (AIV). Perhaps TAM is just a micronized version of Astragaloside IV? Do we know that it is a different molecule than AIV or TA65? Perhaps it is micronized AIV combined with Apigenin or some such thing to kill off cells that might become pathogenic due to broad spectrum activity? TA65 hasn't dropped in price since the release of this, it would make sense that they are intended to be taken together, or I'm assuming such a discovery will eventually be published... $16,800/yr/client, that's some bank! It's starting to make Nicotinamide Riboside look inexpensive at ~$480/yr.

 

3. Is that the 5mg capsules? Or a larger dose? I suppose if one isn't using a highly micronized cycloastragenol that they could still achieve those results with even higher dosing?

 

Thanks for this ampaynz1.

 

Is anyone taking TAM818? Seems very expensive:

 

http://defytimer.com...ement-defytime/

 

 

...

Edited by YOLF, 30 July 2018 - 03:16 PM.

 

I have been looking at TAM-818 ads and noticed it has a patent application and he mentioned his company made it from available molecule and is a synthetic as a plant has never made it on purpose. It was quite interesting to read several of his patents as it shows how few molecules there are in the cells and the difficulty in detecting telomerase. The molecule below is suspect on being related to TAM-818 as it is the main one in the application and also no chemical company makes this exact molecule and different ones on pubchem are different and toxic, so alteration is necessary. Maybe there is a patent in New Zealand. The patent cited here is application is US20090143451A1  . 

 

5-thiophen-2-yl-isoxazole-3-carboxylic acid propylamide having the following structural formula:

 

 

Interesting that it looks like this patent has not been granted (as yet). So in theory other manufacturers could produce this molecule and undercut the sky high prices it's sold at currently.

 

http://defytimer.com...ement-defytime/

So the pentagon with the O and N (the azole) has been substituted with:

 

12. The method according to claim 10, wherein said substituted azole compound has the following structure:

where each R¹, R² and R³ is the same or different and each independently comprises hydrogen or a residue of a group selected from a substituted or unsubstituted acyl, a substituted or unsubstituted amino, a substituted or unsubstituted heterocyle, a substituted or unsubstituted straight-chain or branched C₁-C₂₀-alkyl or C₂-C₂₀-alkenyl (with or without asymmetric carbon atoms), or a halogen, with the proviso that at least one of R¹, R² and R³ is a substituted or unsubstituted five-membered aromatic heterocycle having at least one oxygen or sulfur atom; and where X is selected from nitrogen, oxygen, and sulfur.

It's a racemic of multiple variations of the molecule previously mentioned.

 

I don't have time to figure out if or why it hasn't been approved... the patent at least seems to think that the molecule is new... So could it be something we've already seen? 

 

 

I don't have time to figure out if or why it hasn't been approved... the patent at least seems to think that the molecule is new... So could it be something we've already seen? 

 

I'm not up on patent law, but if this is a manufactured rather than natural molecule it may have to pass more stringent regulations. That might explain why Bill Andrews has had to have this made and exported from New Zealand.  

 

It seems crazy to me that you can find/develop a molecule capable of 16% of the telomerase activation required to prevent shortening, but not get to 100%+. Only one order of magnitude greater (160%) and you could restore all cells to youthful telomere length. I can only assume they don't actually understand how this molecule is doing what it's doing; they've just found it through brute force telomerase assays.

Edited by QuestforLife, 23 August 2018 - 08:24 AM.

It 16% of HeLa . 

But considering HeLa / cancer cells divide at a much faster pace than regular cells and thus need a higher level of telomerase activation in order to restore telomere length, it stands to reason that even 16% of HeLa could be enough to immortalize a human cell line.

 

Edited by marcobjj, 10 September 2018 - 03:50 AM.

Thanks for that Marcobjj, we don't really know what level of telomerase is required by normal human cells to cancel out shortening during normal division, or indeed leave them in a net positive - however I'd guess that 16% of HELA is not sufficient, unless we would have heard much more from Bill Andrews on this compound. From what I've heard and read from him, there is currently nothing better than 16%, and even that can do nothing more than delay normal shortening. He does mention that telomerase preferentially lengthens the shortest telomeres however, so there may be a reversal of the senescent phenotype in some cases (see his latest short book, 'Telomere Lengthening: Curing All Disease Including Aging and Cancer').

Edited by QuestforLife, 10 September 2018 - 02:35 PM.

From memory, the original selling point of cycloastragenol/TA65 was that IT, and not the other options that were found could lengthen the telos of the chromosomes with the shortest telos and inferred that this would restore lost hair that could be restored or at least keep it from falling out and that it wouldn't cause cancer, but rather correct it. 

 

There is perhaps a reason to say that shortest telos get the most rebuild activity from all interventions, though looking at the yamanaka factors, we can learn that there are at least 4 different methods of elongating telos and each has a distinct purpose, all of which are necessary for the immortalization of cells.

From memory, the original selling point of cycloastragenol/TA65 was that IT, and not the other options that were found could lengthen the telos of the chromosomes with the shortest telos and inferred that this would restore lost hair that could be restored or at least keep it from falling out and that it wouldn't cause cancer, but rather correct it.

There is perhaps a reason to say that shortest telos get the most rebuild activity from all interventions, though looking at the yamanaka factors, we can learn that there are at least 4 different methods of elongating telos and each has a distinct purpose, all of which are necessary for the immortalization of cells.

Well you don't need to de-differentiate cells to elongate telomeres, but de differentiating cells does elongate telomeres.

I'm not sure why the shortest telomeres get the most benefit - it might just be that all chromosomes get equal treatment (on average), but that the short strands get a disproportionate length added based on their shorter length.

Edited by QuestforLife, 10 September 2018 - 05:43 PM.

Shorter telos have a lower drag coefficient or the molecular physics equivalent, so they move faster and more easily through the nuclear soup and are more likely to come in contact with whatever is available to build it or break it.  At least that's my guess.

Shorter telos have a lower drag coefficient or the molecular physics equivalent, so they move faster and more easily through the nuclear soup and are more likely to come in contact with whatever is available to build it or break it.  At least that's my guess.

 

Possible. Or maybe it's to do with shorter rather than long, curled strands being more accessible for the telomerase enzyme to clamp onto.

Update:

 

I'm not sure why the shortest telomeres get the most benefit - it might just be that all chromosomes get equal treatment (on average), but that the short strands get a disproportionate length added based on their shorter length.

 

 

You'd expect that as hTERT elongates short telomeres and shortens long ones--

 

In this report, we demonstrated that the telomerase enzymatic component, hTERT, plays a dual role in the regulation of telomere length. It shortens excessively long telomeres and elongates short telomeres simultaneously in one cell, maintaining the optimal telomere length at each chromosomal end for efficient protection. 

https://www.ncbi.nlm...les/PMC4111723/

 

Update:

 

 

It seems we've been waiting an eternity to see some proper trials with HTERT therapy. I hope we can get some more detail on what Libella are doing soon. I suspect they'll save money and only make enough virus for the brain and use an epidural rather than go for a whole body treatment.

Edited by QuestforLife, 17 October 2018 - 10:44 AM.

You'd expect that as hTERT elongates short telomeres and shortens long ones--

 

Also just thought of something quite obvious but which I had overlooked - short telomeres are generally in the 'open' configuration rather than the 'closed', tucked in structure that long telomeres have. Therefore telomerase will associate and 'dock' with short telomeres much more easily.

It seems we've been waiting an eternity to see some proper trials with HTERT therapy. I hope we can get some more detail on what Libella are doing soon. I suspect they'll save money and only make enough virus for the brain and use an epidural rather than go for a whole body treatment.

 

I think you're probably right.

Thanks for the feedback Telo.

Isnt TAM being advertised as 16% Telomerse activation though? so that would make it only 2-3 times more potent than TA65 and not 80-300 times stronger, or am I missing something?

 

 

$500k for 50g of the product. I wonder how much TAM is in each capsule and if microdosing is the reason it's considered only 16% Hela despite the claims of being 300 times stronger than TA65.

 

The back story of TAM-818:

The 314,818^th molecule was actually screened at Sierra Sciences some years ago, back in 2010. It was special in that Sierra Sciences had commissioned this molecule to be made for them at a cost of $500,000 for only 50 grams! The investor who paid for and initiated this project had it in mind that it would be great for use in a skin cream. His sister was highly regarded in the beauty industry with knowledge of cosmetic chemistry and he spoke to her about it, a casual chat on the driveway one day. She heard nothing else about the project for years as the scientists had decided that the compound was too expensive to use and dismissed it.

It was during a regular Friday meeting that the potency of ‘818’ was questioned and revealed that the efficacy of this molecule is so remarkably strong only a small quantity was used to achieve the ground-breaking results shown at Sierra Sciences.  Suddenly the skincare project was once again on the table! It’s strength made it commercially viable. Rachael D’Aguiar was called and with a resounding ‘yes- of course she was still interested’ went about formulating the ideal serum to include TAM-818. 

Edited by marcobjj, 20 October 2018 - 04:18 AM.

$500k for 50g of the product. I wonder how much TAM is in each capsule and if microdosing is the reason it's considered only 16% Hela despite the claims of being 300 times stronger than TA65.

I think 16% Hela means TAM-818 produces 16% of the telomerase Hela cells produces as a positive control. We don't know what level would be required to arrest telomere shortening in normal human cells (ideally we want to do better and re elongate telomeres before letting them gradually shorten again).

But things like methylene blue reduce oxidative stress by around 30% and also give you 30% more population doubling. Which is huge. This also tells me most cells (in culture atleast) senescence due to damage from oxidative stress, and telomere shortening mainly comes from the remaining cells dividing faster to make up for the loss. So immortalised cell lines will still lose lots of cells to oxidative stress, but they'll always have enough remaining cells to divide and keep the culture dividing at the same rate (rather than slowing down and eventually being overwhelmed by the number of senescent cells as with mortal cell lines).

So it might be we don't need to get anywhere near 100% Hela with the right addition of antioxidants.

Just a thought.

I think 16% Hela means TAM-818 produces 16% of the telomerase Hela cells produces as a positive control. We don't know what level would be required to arrest telomere shortening in normal human cells (ideally we want to do better and re elongate telomeres before letting them gradually shorten again).

But things like methylene blue reduce oxidative stress by around 30% and also give you 30% more population doubling. Which is huge. This also tells me most cells (in culture atleast) senescence due to damage from oxidative stress, and telomere shortening mainly comes from the remaining cells dividing faster to make up for the loss. So immortalised cell lines will still lose lots of cells to oxidative stress, but they'll always have enough remaining cells to divide and keep the culture dividing at the same rate (rather than slowing down and eventually being overwhelmed by the number of senescent cells as with mortal cell lines).

So it might be we don't need to get anywhere near 100% Hela with the right addition of antioxidants.

Just a thought.

 

Due to the presence of mitogens in serum, cultured cells tend to divide every 24hrs. Whereas in vivo cells divide every week (rough average). If the doubling rate of cultured cells is 7x that of in vivo cells, then they are also shortening their telomeres at 7 times the rate of normal cells. So it stands to reason that a normal / in vivo cell would only need about one seventh of the amount of telomerase produced by HeLa to be immortalized. Does that make sense, or am I missing something?

Due to the presence of mitogens in serum, cultured cells tend to divide every 24hrs. Whereas in vivo cells divide every week (rough average). If the doubling rate of cultured cells is 7x that of in vivo cells, then they are also shortening their telomeres at 7 times the rate of normal cells. So it stands to reason that a normal / in vivo cell would only need about one seventh of the amount of telomerase produced by HeLa to be immortalized. Does that make sense, or am I missing something?

 

It depends on your starting point, I suppose.

 

If you are the equivalent of a near-to-senescing cell culture, then you need to rejuvenate the cells (by giving them longer telomeres) rather than providing just enough telomerase to keep them dividing (at a presumably slow rate). That would logically require a higher level of telomerase.

 

Whereas if you are young and wish to remain young, a lower level might suffice.

 

If you're in the invidious former situation, there is also the possibility of preferentially killing off the most dysfunctional cells (with senolytics, for example) and then using telomerase activators to help the remainder replace them. You might achieve faster results that way, but it's a bit of a balancing act.

I think 16% Hela means TAM-818 produces 16% of the telomerase Hela cells produces as a positive control. We don't know what level would be required to arrest telomere shortening in normal human cells (ideally we want to do better and re elongate telomeres before letting them gradually shorten again).

 

 

 

Bill / Sierra Sciences use HeLa because "it's the cell line that it's immortal, that produces the least amount of telomerase".

 

 

 

Anyone have any updates on Bill Andrew's telomerase trial through Libella Gene Therapeutics or any other telomerase activator news?

 

I think at RAADFEST he said there'd be an update on the Libella trial in Feb 2019 (after the treatment of the first Alzheimer's patient).

No updates from Mr. Andrews so far but Bioviva is also in the biz now. They're offering free experimental treatment in Mexico for select Alzheimer patients.

Are you sure it's free? Last time I checked they tried to charge me $30,000

they say free 62k treatment.

 

https://mailchi.mp/b....com/alzheimers

No updates from Mr. Andrews so far but Bioviva is also in the biz now. They're offering free experimental treatment in Mexico for select Alzheimer patients.

 

According to this interview, https://bengreenfiel...mere-testing/, Libella (the company that has licenced Bill Andrew's gene therapy) should be treating their first patient in May 2019.

 

From what I can tell the difference between Libella's offering and Bioviva's, is that Bioviva are specifically targeting the brain so require a smaller dose, whereas Libella are treating the whole body, but with the primary endpoint still being treatment of Alzheimer's Disease. This probably explains why the Bioviva treatment costs much less. On that subject, I also read it was free for a limited number of patients, although you still have to pay for travel and follow up testing. Maybe re-apply Ceridwen?

 

Changing tack slightly, has anyone on this forum tried Bill Andrews TAM-818 pills you can buy from Defytimer? They are even more expensive that TA-65, but claimed to be 16% of HELA (compared to ~6% for TA-65). Biovailability at this time is unknown, though Bill told me he believes it will be good based on the design of the molecule (following Lipinski's rule of five).