23 replies to this topic

[Believer]

The main thread is a total mess with so many irrelevant posts but even in spite of that I did skim through it. There is not much to read other than reports of vivid dreams and such, which is totally irrelevant to the question of age reversal.

 

Has anyone here on Longecity experienced:

1. Removal of skin wrinkles and sagging?

2. Changing of fatty deposits in skin to a more youthful state?

3. Reversal of graying of hair?

4. Just in general a more youthful physical look?

5. Any physical changes at all?

 

My 75 year old father has the money to take it at 10-20mg every day for years. If it really works it would be worth the cost.

[QuestforLife]

Good questions.
All of the evidence for epitalon and indeed most peptides is Russian, led by professor Khavinson. I’ve done 3 cycles of epitalon over the last year, injecting 10mg every day or every other day, adding up to approximately 100-150mg per cycle, depending on the cycle. I experienced better sleep and improved weightlifting/recovery. I have not noticed a younger appearance. Based on the renewal time of the skin compared to the renewal time for WBCs (where telomere lengthening has been noted by users), I’d expect you’d need many cycles before there would be a noticeable effect on skin. i.e. leukocytes turnover in 6 days, the skin takes a month (approximately). So, if you’re dosing for 20 days, you’ll be elongating telomeres of leukocytes through 3 total replacements, but possibly not all your skin will have turned over in that period (I’m assuming here that cell division is necessary to elongate telomeres). Adding to that you really want to be elongating the telomeres of stem cells, and presumably these divide less often to supply the progenitors that do most of the dividing to supply the tissues, and you can understand why you shouldn’t expect overnight age reversal even if epitalon is as powerful a telomerase activator as Khavinson claims. So, did my leukocyte telomeres get longer? Yes. After 2 cycles of epitalon over a year and a half since my first telomere test, and a month after my last dose of epitalon, a test showed my leukocyte telomeres were longer. My shortest telomeres had increased by 900 base pairs, my median length telomeres by 300bp and my mean length telomeres by 200bp. This is consistent with epitalon rescuing the chromosomes with the shortest telomeres but having less effect on the average length. One final note, even if your father has enough money to inject daily I’d still recommend cycles in order that there is proper replacement of somatic tissues, giving time for the benefits to stem cells to become apparent.

[Believer]

One final note, even if your father has enough money to inject daily I’d still recommend cycles in order that there is proper replacement of somatic tissues, giving time for the benefits to stem cells to become apparent.

I very much appreciate your informative reply
My father does indeed have enough money. He is also old and dying so why not take the financial chance? I don't understand why people say it is expensive.
A 30 day cycle of 10mg a day N-Acetyl-Epitalon-Amidate costs a mere 65 USD per 10 vials, so 195 USD for a month's cycle. I say a mere 65 USD because we spend way more on vitamin and other supplements that hardly do a tenth of what epitalon is claimed to do in studies. You can get it cheaper if you search for the right company. If you buy bulk powder of epitalon non-amidated and non-acetylated it will be significantly cheaper although I suspect it's quite difficult to make the freeze dried powder into usable sterile injectibles if you don't have a laboratory like the companies do.

Cycloastragenol on the other hand is extremely expensive for what you get in terms of anti-aging effects. It doesn't even elongate telomeres, it only slows down the rate of shortening. But if you buy it as bulk powder from Alibaba you can get it for less than half the price of commercial products.

It is not your fault but I do not understand the sentence in bold in the quotation. I've tried to re-read it multiple times. Please explain what you mean.

I hate yet to find out why the Russians cycle epitalon. I've looked through many threads, think I read the reason somewhere but forgot it. Is it for the reason you stated in the bold text?

 

Thanks for your reply

 

[Turnbuckle]

One final note, even if your father has enough money to inject daily I’d still recommend cycles in order that there is proper replacement of somatic tissues, giving time for the benefits to stem cells to become apparent.

 

It is not your fault but I do not understand the sentence in bold in the quotation. I've tried to re-read it multiple times. Please explain what you mean.

 

 

 

 

You're right. That sentence doesn't make sense, as stem cells are only going to replace senescent or otherwise damaged cells. So first you have to have sufficient stem cells, which is generally lacking in the elderly, and second, increasing telomere length will give epigenetically old somatic cells a new lease on life, thus delaying replacement.

[QuestforLife]

It does make sense. Human cells keep a tight control on telomerase production as the TERT gene is near the end of the chromosome, so the tail of the telomere inhibits further telomere production. When cells divide is an opportunity to overcome this limitation. Therefore the cells that divide the most will have the most telomerase. So it is my (educated) guess that more telomerase does extend the life of progenitor and somatic cells (as Turnbuckle says). This could be either a good or bad thing depending. That's why I advocate cycles.

Another reason is cancer. If you had a (so far) benign growth, you don't want to help it get big enough to turn malignant. Of course your immune system will be stronger too, so it maybe won't be an issue. But I'd still err on the side of caution and cycle.

So in conclusion, a cycle of epitalon can massively increase leukocyte telomere lengths but have a smaller benefit to the underlying stem cell pool. But that's the benefit that you really want.

[Turnbuckle]

It does make sense. Human cells keep a tight control on telomerase production as the TERT gene is near the end of the chromosome, so the tail of the telomere inhibits further telomere production. When cells divide is an opportunity to overcome this limitation. Therefore the cells that divide the most will have the most telomerase. So it is my (educated) guess that more telomerase does extend the life of progenitor and somatic cells (as Turnbuckle says). This could be either a good or bad thing depending. That's why I advocate cycles.
 

 

There is indeed a cellular mechanism for keeping telomeres from getting too long, and this involves a trimming mechanism. As for "cells that divide the most will have the most telomerase," not quite true. Transit amplifying cells (TACs) divide the most. That's where you will see epigenetic aging occurring in many tissues, because they take the load of producing new cells, while stem cells are held in reserve. And while they produce telomerase, the level is constrained to less than immortality, otherwise they will keep getting epigenetically older and more dysfunctional while not being replaced. Long life is associated with replacement of cells, not with conservation of old cells--

 

Clearly long-lived animals protect the steady state of their tissues by continuous replacement of the cells that regularly differentiate and die. An adult human contains approximately 10^12 rapidly multiplying cells. During a typical~30 000 day lifespan (~80 years), each person makes and discards an enormous number of cells from the bone marrow, skin, and gastrointestinal track each day [42]. 

https://www.ncbi.nlm...les/PMC3370416/

 

 

Increasing telomere lengths should improve health in the short term by reducing senescent cells and their inflammatory secretions, but eventually you will have to pay for that, for as cells get epigenetically older with each division, they get more and more dysfunctional. Thus resetting the telomeric clock is robbing Peter to pay Paul. The better solution is to expand stem cells to a more youthful level without interfering with the cells' internal clocks, and let the body replace old cells as it did when you were younger. The body, after all, knows what it is doing. it just runs out of functional stem cells at the front end.

 

As for cycles, there are some 200 cell types in the body. Some cycle very rapidly, and some very slowly. So which to target? Beyond that, increasing telomeres in even a fast cycling system such as skin cells can take months to return to normal after telomerase extending treatments. At least that's what I've seen from epigenetic tests when I experimented with telomerase enhancers.

 

Edited by Turnbuckle, 16 February 2020 - 11:31 AM.

[QuestforLife]

Increasing telomere lengths should improve health in the short term by reducing senescent cells and their inflammatory secretions, but eventually you will have to pay for that, for as cells get epigenetically older with each division, they get more and more dysfunctional. Thus resetting the telomeric clock is robbing Peter to pay Paul. The better solution is to expand stem cells to a more youthful level without interfering with the cells' internal clocks, and let the body replace old cells as it did when you were younger. The body, after all, knows what it is doing. it just runs out of functional stem cells at the front end.

As for cycles, there are some 200 cell types in the body. Some cycle very rapidly, and some very slowly. So which to target? Beyond that, increasing telomeres in even a fast cycling system such as skin cells can take months to return to normal after telomerase extending treatments. At least that's what I've seen from epigenetic tests when I experimented with telomerase enhancers.

I agree with much of what you say Turnbuckle, with some subtle differences, which unfortunately lead to quite different conclusions. Of course there are lots of subtleties with different cell types and the inflence of the ECM, if any, which can control the behaviour of the cells in it. But the key issue is that you say telomerase can only lead to short term benefit, because cells need to be replaced. I agree that cells should be replaced. But the problem is the source of the replacements - stem cells - have to have sufficient telomerase to make those replacements. And there is clear evidence in the declining tissue telomere lengths with age (the cyclical short term decline and refresh from replacement overlays a consistent decline over multiple cycles) that stem cells fail to do that. So any therapy without this, i.e. expanding stem cell pools without sufficient telomerase, will only work in the short term. Eventually those pools will either shrink irreversibly,no longer function properly, or worse become cancerous. Now nothing is certain in the biology of aging, maybe we can coax enough telomerase out of adult stem cells with the right external signalling, or maybe there are pluripotent stem cells hidden in the body to be activated with the right signal. But I think you are placing way too much trust is methylation aging tests. I use them myself. But they need to be interpreted with caution. You need to be sure you're not running down your stem cell supplies just to get a younger reading on the test.

Edited by QuestforLife, 16 February 2020 - 01:25 PM.

[Turnbuckle]

I agree with much of what you say Turnbuckle, with some subtle differences, which unfortunately lead to quite different conclusions. Of course there are lots of subtleties with different cell types and the inflence of the ECM, if any, which can control the behaviour of the cells in it. But the key issue is that you say telomerase can only lead to short term benefit, because cells need to be replaced. I agree that cells should be replaced. But the problem is the source of the replacements - stem cells - have to have sufficient telomerase to make those replacements. And there is clear evidence in the declining tissue telomere lengths with age (the cyclical short term decline and refresh from replacement overlays a consistent decline over multiple cycles) that stem cells fail to do that. So any therapy without this, i.e. expanding stem cell pools without sufficient telomerase, will only work in the short term. Eventually those pools will either shrink irreversibly,no longer function properly, or worse become cancerous. Now nothing is certain in the biology of aging, maybe we can coax enough telomerase out of adult stem cells with the right external signalling, or maybe there are pluripotent stem cells hidden in the body to be activated with the right signal. But I think you are placing way too much trust is methylation aging tests. I use them myself. But they need to be interpreted with caution. You need to be sure you're not running down your stem cell supplies just to get a younger reading on the test.

 

 

Embryonic stem cells are immortal. Until recently it was thought those disappeared during development, but in fact a reservoir still exists in the adult that circulates in the blood, providing a backup to adult stem cells. They were missed because of their small size.

 

See: Evidence that the population of quiescent bone marrow-residing very small embryonic/epiblast-like stem cells (VSELs) expands in response to neurotoxic treatment

 

And—

 

VSELs Maintain their Pluripotency and Competence to Differentiate after Enhanced Ex Vivo Expansion

 

The very small embryonic-like stem cells (VSELs) are known as a subset of adult pluripotent stem cells able to differentiate to all three germ layers. However, their small number and quiescence restrict the possibility of their use in cell therapy.

https://www.ncbi.nlm...les/PMC6013546/

 

 

So it is only necessary to banish quiescence and expand their numbers in vivo, in which case an unlimited source becomes available. That’s what I believe is happening in my SC protocol.

Edited by Turnbuckle, 16 February 2020 - 02:02 PM.

[QuestforLife]

Embryonic stem cells are immortal. Until recently it was thought those disappeared during development, but in fact a reservoir still exists in the adult that circulates in the blood, providing a backup to adult stem cells. They were missed because of their small size.

See: Evidence that the population of quiescent bone marrow-residing very small embryonic/epiblast-like stem cells (VSELs) expands in response to neurotoxic treatment

And—


So it is only necessary to banish quiescence and expand their numbers in vivo, in which case an unlimited source becomes available. That’s what I believe is happening in my SC protocol.

Yes I've read those papers with interest. I'd love to believe them. It's plausible that some traces of the embryo remain in the body in tiny numbers. Must be a reason and most likely such cells are still there because they're almost impossible to wake up. Great if you've found them, but potentially dangerous too. If you did manage to symmetrically expand their numbers enough you'd basically have an undifferentiated teratoma. Maybe that won't happen if they're in the bloodstream. But to go from the marrow to the blood they're probably not embryonic anymore.

Edited by QuestforLife, 16 February 2020 - 03:37 PM.

[Turnbuckle]

Yes I've read those papers with interest. I'd love to believe them. It's plausible that some traces of the embryo remain in the body in tiny numbers. Must be a reason and most likely such cells are still there because they're almost impossible to wake up. Great if you've found them, but potentially dangerous too. If you did manage to symmetrically expand their numbers enough you'd basically have an undifferentiated teratoma. Maybe that won't happen if they're in the bloodstream. But to go from the marrow to the blood they're probably not embryonic anymore.

 

 

See the first link I provided in post 8 above--

 

The salient observation of this report is that a quiescent population of BM-residing VSELs responds by expansion to exposure to the neurotoxin KA. In many previous models of tissue/organ injuries, such as heart infarct, stroke, skin burns, sodium iodide-induced retinal damage or Crohn's disease, we and others have demonstrated that VSELs can be mobilized in stress situations from BM into PB, assuming that BM is the primary source of these cells [11,13,24–26]. In this report, we provide evidence that a quiescent population of BM-residing VSELs indeed proliferates and expands in BM in response to neurotoxic damage, and at the same time, undergoes specification into the neural lineage, as revealed by RQ-PCR analysis of neural gene expression and immunohistochemical staining. This process seems to precede subsequent egress/mobilization of these cells from BM into PB.

 

[QuestforLife]

Is it plausible C60 could get into the bone marrow, or do you think such quiescent cells exist elsewhere, Turnbuckle? I seem to remember a paper saying they were in other tissues too. Either way it seems they are only mobilised as a last reserve.

It seems a stretch to say the least, but based on your reported results could be true.

Anyway we've drifted from the topic. No doubt you'll continue to avoid telomerase activators and I'll continue to use them. So far I've managed to elongate telomeres and decrease epigenetic age using ROCK inhibitors in addition to the TAs.

It would be interesting to know your telomere lengths, Turnbuckle. If embryonic cells really are expanding then you'd expect a benefit to telomeres too.

[Turnbuckle]

Is it plausible C60 could get into the bone marrow, or do you think such quiescent cells exist elsewhere, Turnbuckle? I seem to remember a paper saying they were in other tissues too. Either way it seems they are only mobilised as a last reserve.

It seems a stretch to say the least, but based on your reported results could be true.

Anyway we've drifted from the topic. No doubt you'll continue to avoid telomerase activators and I'll continue to use them. So far I've managed to elongate telomeres and decrease epigenetic age using ROCK inhibitors in addition to the TAs.

It would be interesting to know your telomere lengths, Turnbuckle. If embryonic cells really are expanding then you'd expect a benefit to telomeres too.

 

There seem to be multiple backup systems operating in the body, such as free floating mitochondria that can presumably be captured by somatic cells. Likewise there are these very small embryonic cells (VSELs) floating around that can replenish stem cell niches.

 

VSELs Þ SCs  Þ TACs Þ Somatic cells

 

The intervention I propose its all the way to the left, and will increase the throughput. Telomere extension is in the middle at TACs and SCs, and will decrease the throughput.

 

Applying my SC protocol will likely increase the length of telomeres as a side effect, as newly minted TACs and the somatic cells derived from them should have longer telomeres. But that’s not important. The important thing is their epigenetic programing will be ne novo, and thus very young, along with longer telomeres. While longer telomeres on epigenetically old cells is not a good idea.

 

As for C60 getting into bone marrow, it obviously does, as some of these epigenetic tests use white blood cells as the DNA source, and I’ve not seen any notable difference between tests using buccal cells and those using white blood cells.

Edited by Turnbuckle, 16 February 2020 - 07:36 PM.

[QuestforLife]

VSELs Þ SCs Þ TACs Þ Somatic cells

The intervention I propose its all the way to the left, and will increase the throughput. Telomere extension is in the middle at TACs and SCs, and will decrease the throughput.

That's a nice way of putting it. You are pushing from the left (assuming the theory is correct) and presumably clearing the right when you use senolytics.

My approach isn't quite as simple as extending telomeres in the middle. I'm actually trying to push cells back up the epigenetic hierarchy right to left by interfering with their size and structure, primarily using ROCK inhibitors.

Let's see how the next few years pans out in terms of our results. I'm personally happy we're trying very different approaches. It's a pity the tests are still so expensive.

[Believer]

QuestForLife you may have said it before and I apologize if I forgot but how old are you? You don't have to be specific just what age range, 20-30, 40-50, 60-70?

Do you think your biological age fits your chronological age?

 

 

[QuestforLife]

QuestForLife you may have said it before and I apologize if I forgot but how old are you? You don't have to be specific just what age range, 20-30, 40-50, 60-70?
Do you think your biological age fits your chronological age?

I'm 41. I don't need to guess how well my interventions have worked. I've done 3 (soon to be 4) DNA methylation age tests from Zymo, 2 telomere tests from Lifelength, and multiple blood work (from 2015 onwards).

My blood works have always been very good, but until the last set of tests in 2019 (based on interventions done in 2018/19) I was ageing on schedule based on methylation and telomere age tests. Lots of interventions I tried did nothing.

From 2018 I started my SES (statin-epitalon-sartan) cyclical protocol. It's taken 2-3 years off both my DNA methylation age and telomere age so far.

I also input this year's blood work results into PhenoAge calculator. It came out at 30, which I don't believe - but I do believe the fact it's reversed 2 years from the last set of results. So all my results seem to roughly be in agreement.

It's expensive, but I'll keep testing to keep improving what I'm doing.

Edited by QuestforLife, 16 February 2020 - 10:34 PM.

[Turnbuckle]

I also input this year's blood work results into PhenoAge calculator. It came out at 30, which I don't believe - but I do believe the fact it's reversed 2 years from the last set of results. So all my results seem to roughly be in agreement.
 

 

 

I take it this is not an actual epigenetic measurement?

[QuestforLife]

I take it this is not an actual epigenetic measurement?

The PhenoAge calculator uses certain blood test results to give an estimate of methylation age. You can get an Excel spreadsheet to do it for yourself off the web. There should be a link in the Biomarkers page for mine (and others') results. It claims to be pretty accurate but don't know how accurate it is compared to say, Zymo's DNA methylation age test (the best). It's certainly a lot cheaper.

[Turnbuckle]

The PhenoAge calculator uses certain blood test results to give an estimate of methylation age. You can get an Excel spreadsheet to do it for yourself off the web. There should be a link in the Biomarkers page for mine (and others') results. It claims to be pretty accurate but don't know how accurate it is compared to say, Zymo's DNA methylation age test (the best). It's certainly a lot cheaper.

 

But does it look at actual methylation patterns? Apparently not. Nothing on the list of blood tests you provided on the biomarkers page looks at methylation patterns. Whereas the 2 actual epigenetic tests you reported do-- 

 

MyDNage (2018)

Chronological Age: 39

Methylation DNAge 39

 

Zymo (2019)

Chronological Age: 40

Methylation DNAge: 38

 

So it appears that PhenoAge, which gave you an "estimated" methylation age of just under 30,  is not a reliable substitute for tests that actually measure methylation patterns.

[QuestforLife]

 

But does it look at actual methylation patterns? Apparently not. Nothing on the list of blood tests you provided on the biomarkers page looks at methylation patterns. Whereas the 2 actual epigenetic tests you reported do-- 

 

MyDNage (2018)

Chronological Age: 39

Methylation DNAge 39

 

Zymo (2019)

Chronological Age: 40

Methylation DNAge: 38

 

So it appears that PhenoAge, which gave you an "estimated" methylation age of just under 30,  is not a reliable substitute for tests that actually measure methylation patterns.

 

 

I'm not suggesting that it is a reliable substitute for an actual DNA methylation test, although that is the claim of the authors, see: https://www.ncbi.nlm...les/PMC5940111/

 

 

 

 Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.

 

I will continue to use proper DNA methylation tests until such time as it can be shown to my satisfaction that blood tests are a reliable substitute. I'm due to take another DNA methylation test soon, which may shed further light on the situation.

Edited by QuestforLife, 17 February 2020 - 10:00 AM.

[Turnbuckle]

I'm not suggesting that it is a reliable substitute for an actual DNA methylation test, although that is the claim of the authors, see: https://www.ncbi.nlm...les/PMC5940111/

 

 

 

 

Look at FIG. S5 B from that paper. The correlation of their estimated age to chronological age of caucasians is only .65, not nearly as good as tests using actual methylation data. And your own results indicate that their estimate didn't come close to actual methylation tests. Compare that to results reported by Horvath on the right.

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Edited by Turnbuckle, 17 February 2020 - 11:53 AM.

[QuestforLife]

Looks like we'll be using direct methylation tests for the foreseeable, then. 

[QuestforLife]

To sum up our discussions Turnbuckle is aiming to expand out small numbers of embryonic cells in the bone marrow in order to solve telomere shortening and epigenetic aging and rejuvenate peripheral tissues. I am aiming to partially de-differentiate cells using (primarily) ROCK inhibition, combining this with telomerase activation in order to rejuvenate tissues.

Turnbuckle thinks telomerase activation will run into trouble because it will extend the life of intermediate progenitor cells and block the expansion of epigenetically younger stem cells. He experienced an increase in epigenetic age when he added telomerase activators to his protocol. I think this is not a problem in my protocol given the co-current application of de-differentiation agents and my intermittent dosing.

I am concerned that Turnbuckle’s protocol might expand stem cell numbers by reducing telomere lengths. Turnbuckle counters that embryonic cells will prevent this. I did not experience a decrease of epigenetic age on Turnbuckle’s protocol but did on my own protocol. I think Turnbuckle should get a high-quality telomere measurement to prove that embryonic cells are preventing shortening.

It is possible that our different results are due to our different ages (66 vs 41). In any case we are both committed to ongoing experimentation and most importantly, testing.

[eigenber]

To sum up our discussions Turnbuckle is aiming to expand out small numbers of embryonic cells in the bone marrow in order to solve telomere shortening and epigenetic aging and rejuvenate peripheral tissues. I am aiming to partially de-differentiate cells using (primarily) ROCK inhibition, combining this with telomerase activation in order to rejuvenate tissues.

Turnbuckle thinks telomerase activation will run into trouble because it will extend the life of intermediate progenitor cells and block the expansion of epigenetically younger stem cells. He experienced an increase in epigenetic age when he added telomerase activators to his protocol. I think this is not a problem in my protocol given the co-current application of de-differentiation agents and my intermittent dosing.

I am concerned that Turnbuckle’s protocol might expand stem cell numbers by reducing telomere lengths. Turnbuckle counters that embryonic cells will prevent this. I did not experience a decrease of epigenetic age on Turnbuckle’s protocol but did on my own protocol. I think Turnbuckle should get a high-quality telomere measurement to prove that embryonic cells are preventing shortening.

It is possible that our different results are due to our different ages (66 vs 41). In any case we are both committed to ongoing experimentation and most importantly, testing.

QuestforLife - You suggest using ROCK inhibitors in conjunction with epitalon. Would you mind elaborating the specifics of your protocol, such as dosage, frequencies, etc.? 

Are there any ROCK inhibitors to be found among supplements? This article mentions baicalein, although it's not clear he's referencing it as a ROCK inhibitor or a 5-LOX inhibitor, or both. https://www.academia...ue_rejuvenation

[QuestforLife]

QuestforLife - You suggest using ROCK inhibitors in conjunction with epitalon. Would you mind elaborating the specifics of your protocol, such as dosage, frequencies, etc.? 

Are there any ROCK inhibitors to be found among supplements? This article mentions baicalein, although it's not clear he's referencing it as a ROCK inhibitor or a 5-LOX inhibitor, or both. https://www.academia...ue_rejuvenation

 

I don't buy the bioavailability of baicalein; from my research tongkat ali or phloretin looked a much better bet for ROCK inhibition. The best 5-Lox inhbitor available as a supplement seems to be extract of boswellia (AKBA). The dosing window seems to be tricky however, as crushing down inflammation too much appears to make me vulnerable to infection with various viruses. From the pharmaceutical point of view there is lots on my thread about the statin-sartan protocol, which I've had positive results from. Statins can inhibit ROCK even at low doses, and sartans decrease tgf-b. The dose I've used is 5mg atorvastatin, 20mg losartan, everyday for 20days, twice a year.