49 replies to this topic

[William Sterog]

I have read that Taurine and Sulforaphane both increase H2S.

[OP2040]

William,

After reading more of the literature, it looks like you are correct.  I am taking supps for both on and off.  The problem with all these myriad of targets appears to be that twofold.  First, how do we know we are actually reaching our target and a change is happening?  The more biochemical pathways, the more likely your target will not be reached, or your effect will be blunted.  This relates to the second problem, and potential solution.  As tempting as all these numerous potential targets are, I always seem to come back to the idea that the more upstream the better.  Klotho is as far upstream as I can tell for this pathway.  It should strongly effect every other target mentioned in this thread.   In contrast, most of the other targets are much further downstream and may or may not have an effect on the more upstream targets.  For the record, this is how I see the parts of the pathway I'm interested in from higher to lower:

Klotho > Redox homeostasis (Thioredoxin) > H2S/NO

 

Obviously it's much more complicated than that, but it's at least clear to me that the redox management cascade caused by Klotho is a huge part of it's longevity effects, and that the redox system itself is quite complicated.  Although Thioredoxin is another great target and is also proven promoter of lonegevity and health, why not try to go higher which would effect both Thioredoxin and other systems.

 

Anyway, so my point is that a lot of my musings on some of these lower targets is because I didn't expect it to be next to impossible to get the Klotho thing organized.  Whereas, things like Taurine and Sulforaphane are cheap and easy to get.  And I'm absolutely certain that Klotho would move the ball forward, whereas some of these other things merely slow the "rate of decline".

 

For the record, I do have one fairly serious health issue for which there is no explanation, as I do everything right by the standards of the mundane medical community.  That is what got me involved with all of this.  I have always been the type that wants to get to the root cause of a problem, rather than just accepting fate.  My point is that with this health issue, I can easily tell whether something has worked or not, and it's a big goose egg for Taurine and Sulforaphane, and some others.  But I am absolutely convinced that Klotho is a game changer.

 

 

[mikey]

Orion22,

 

I am new to group buys, so yes I am either going to need some guidance or it will take some time.  Also, the entire point of the thread is to answer some of the questions you are posing.

 

Why Compound H?  That is my personal choice because it is the cheapest, and still shows much the same beneficial effects as the full Klotho version.  I'm very open to a discussion about why one of the other two options would be better, but so far no one is objecting to that path.

 

How much?  Very good question.   The mouse study that shows great benefits was done for two weeks, daily @ 15 mg/kg IP.  The HED dose for that is something like 1.2 mg/kg, so for a 185 lb man like myself would be 100mg, so very doable.

 

Why me? I really don't care who does the group buy, so if someone else will step in, I'd be more than happy to let them.  As for safeguarding things, I would like to have everyone to purchase and organize their own delivery after the buy is organized.  I have no desire to exchange money, or repackage and ship product.  This is how another group is doing the Trehalose buy, but it may not be feasible for a more esoteric compound like this.

 

I have no idea what the details would be until I place a few requests and then find out what t he companies shipping and payment policies would be.  Before I do that, I wanted to get a decent amount of people involved, and answer some of our questions.

 

For a start, does anyone object to going with compound H?  If so, lets have the discussion.  If not, I will move forward.  I obviously can't look for quotes without getting everyone on board with what we're actually going to purchase.

 

I am interested in Compound H specifically to see if it improves blood pressure. The daily price is high, though. I have a professional capacity to purchase chemicals. Perhaps I can find a better solution. I think what we need is a company that will produce individual sterile vials with a specific dose. We don't want the buyer to have to split up doses for each of us. It's late. I'm going back to sleep. I'll research sources tomorrow during the day.

[cassioBJJ]

For me we can go with Compound H.

[OP2040]

I am interested in Compound H specifically to see if it improves blood pressure. The daily price is high, though. I have a professional capacity to purchase chemicals. Perhaps I can find a better solution. I think what we need is a company that will produce individual sterile vials with a specific dose. We don't want the buyer to have to split up doses for each of us. It's late. I'm going back to sleep. I'll research sources tomorrow during the day.

 

mikey,

First of all, thank you so much for your offer of help. I would love to pursue this with someone who knows more about labs and chemical companies.  Having said that, I don't want to just push it off on someone else, and create a burden for others.  As I see it, we need to determine which substance we want to purchase first, and for me money doesn't matter so much for the first round.   That round can be for proof of principle. 

 

As for blood pressure, you nailed it.  This is the thing that this pathway should effect the most, and it is easy to measure, and lots of people have it.    Thioredoxin is where I saw the best evidence of this in a mice study.  But there are a couple studies that show this for Compound H, and it's clear that Klotho controls the TRX system.  An alternative pathway is to inhibit TXNIP (thereby increasing TRX1) which increases with age.  But I haven't seen any good interventions for that. Either way, blood pressure is an accurate, cheap and easy testing protocol that we can use for our proof of principle.

[mikey]

BP is definitely one thing that I am addressing with aging. So I am interested.

The way it works to have it made is to first have enough demand that one can get a quality lab to quote.

 

As to Compound H, it appears to be required to be administered via either subQ or IV. Someone with more knowledge of biochemistry please chime in.

 

I, personally, don't want to do IV unless I am certain that the results are worth it and then I will need to study technique. Not appealing, but I would acquiesce if it did what it's supposed to do, without causing harm.

 

The lab quote will be to ask the lab to aliquot X mg per sterile vial.

We need to know how long a solution of it will last using bacteriostatic water, to determine how much the lab will put in each vial.

 

If a daily dose is 100 mg and it will certainly be stable for ten days refrigerated, then the lab will be asked to quote for 1,000 mg per vial.

 

I think that we want to pay a bit extra to make sure it's TFA-free. 

 

Does one want to do cycles of it, perhaps in daily two-week cycles and then take a break? Details about administration need to be determined. 

This seems worthwhile. I hope that it attracts more of the seasoned scientists on LongeCity for their coaching. I will message a few.

 

Regards,
Mikey

[OP2040]

great info mikey,

 

SubQ is the way to go as long as that works. 

 

Also, you're right we need to figure out dosing.  It would be great to get enough for daily dosing for two weeks at 100mg to try to replicate the mouse study.  But even a 1 time dose should be a great test to start with.  I'll revisit the Compound H studies to see if anything more can be gleaned about the dosing schedule.

 

I think we definitely have enough interest.  It looks like we could easily get 20 people or more interested.  I've seen a couple other group buys flame out while the organizer(s) try to herd cats.  I wonder if it would be better to just get a quote first based on perceived interest, or maybe a few quotes to see where the price breaks are.  I'm so interested in this buy that if we didn't get as many people as expected, I'd happily mop up the extra product myself, within reason of course.

[recon]

I’ll pull out from this group buy, I’m sorry.
There weren’t repercussions to the lack of communication of the previous few I’ve seen.

It’ll be great to see how this progress though.

Edited by recon, 14 August 2018 - 10:48 AM.

[Painkillerrr]

Im interested as well. I would not use component h, there is leterally evidence about its safety not even in mice( in vivo), plus there are substances safe safe in other animal models but not in human.

I dont know you but i would rather spend 200$ for a pretty safe stuff then 50 or 10$ for a way risky one.

“Real klotho” is more exepensive but at least it should be the same we have in our body, elevating it could be somehow toxic anyway but still way safer then any other alternative.

The dose could be as low as 10ug, still exensive but im pretty sure it would be worth it.

Should we make a group on discord or something similar??

Edited by Painkillerrr, 07 September 2018 - 09:05 AM.

[OP2040]

I agree that actual Klotho is the high road and would prefer it far more than the others.  But it is super-expensive!  This group buy probably won't go anywhere for the same reason most of them don't.  It is just too expensive.  FOX04-dri is the only semi-successful group buy I've seen so far, and a lot of that is because people only want or need one dose, not because it's any cheaper. 

 

It's sad because there are more good potential targets and ways to target them than every before in history.  But we simply can't access them.  Very frustrating!

[Painkillerrr]

are more good potential targets

For example?

[OP2040]

Bump...

 

I haven't given up on my Klotho quest.  However, I realize that we are just not there yet and another strategy may be needed.  As with other interventions for which a drug is too expensive or hard to get, I'm trying to find natural substances that may boost Klotho levels.  So far this is the only article I've found.  Unfortunately it is not much to go on.

 

https://www.ncbi.nlm...pubmed/15339392

 

Unfortunately, this is just based on an in vitro cellular assay.  Does anyone know of any other studies on natural substances that are Klotho promotors?

 

The good news is we're finding out more everyday about the pathway.  It's now clear that the pathway is affected by FGF21, and affects the Thioredoxin redox system.  Here's an article just out today that effects FGF21 downstream with a protein, and we get the expected beneficial results (in mice).

 

https://medicalxpres...al-protein.html

 

So it seems clear that we will be able to target this pathway one way or another.  The main issue with Klotho is that it's a lifetime commitment.  You need to keep it upregulated for long periods of time.  For that reason, we may need to rely on natural substances for now, and wait for a one-time gene therapy in the future. 

[OP2040]

I found an even better natural substance that is thought to increase Klotho levels:

 

https://www.nature.c...icles/srep34597

 

Rhein or Cassic Acid is a derivative of Rhubarb.  Unfortunately, it is one of those things that, although natural, can only be bought from a lab.  Ali Baba once again has it at reasonable prices whereas US labs have it at highway robbery prices.  I'm finding that any natural substance that really does work seems to be locked down and never sold as a supplement.  Why should an extract of rhubarb not be available?  Does anyone have experience with this substance.

 

Either way, it seems like a good option. 

[OP2040]

I take that back, Rhein could be a great candidate for a group buy.  The study dose comes out to an HED of 800mg for me, so starting off with 100mg seems like a good place to start.  I am seeing a lot of quotes from American companies that are down to ~$50-$75/100mg, and they don't seem to have the ordering locked down, probably because this is just a rhubarb extract.  Another argument for this, aside from he fact that it promotes Klotho, is that the study hints at the idea that it turns Klotho functioning back on like a switch.  If that is true, then one need not take it continuously to reap the benefits of Klotho.

 

Oh and one other thing about the study.  My stand at attention whenever I see key words like "reverse" when it comes to aging, or in this case fibrosis.  Fibrosis is usually the end-game as far as organ damage goes, so if and when it can be demonstrated to be reversed by anything, that is a huge deal.  In this case, the reversal was quickly attained after an induction of toxicity, which cannot be assumed to be how fibrosis in aging works.  However, it is a difficult trick to pull off and well worth mentioning.

 

A group buy would allow for a much cheaper price I'm sure, anyone interested?  I am going to try @ 100mg by myself even if no one else in interested.  Even if you don't want to go in on it, would like to here your thoughts on the study....

Edited by OP2040, 20 November 2018 - 06:08 PM.

[cassioBJJ]

I take that back, Rhein could be a great candidate for a group buy.  The study dose comes out to an HED of 800mg for me, so starting off with 100mg seems like a good place to start.  I am seeing a lot of quotes from American companies that are down to ~$50-$75/100mg, and they don't seem to have the ordering locked down, probably because this is just a rhubarb extract.  Another argument for this, aside from he fact that it promotes Klotho, is that the study hints at the idea that it turns Klotho functioning back on like a switch.  If that is true, then one need not take it continuously to reap the benefits of Klotho.

 

Oh and one other thing about the study.  My stand at attention whenever I see key words like "reverse" when it comes to aging, or in this case fibrosis.  Fibrosis is usually the end-game as far as organ damage goes, so if and when it can be demonstrated to be reversed by anything, that is a huge deal.  In this case, the reversal was quickly attained after an induction of toxicity, which cannot be assumed to be how fibrosis in aging works.  However, it is a difficult trick to pull off and well worth mentioning.

 

A group buy would allow for a much cheaper price I'm sure, anyone interested?  I am going to try @ 100mg by myself even if no one else in interested.  Even if you don't want to go in on it, would like to here your thoughts on the study....

 

I gave it a try for Rhubarb extract which seems to be the same than Rhein, but I didn't get any improvements on my renal blood tests (serum creatinine, urea, uric acid, etc). Maybe Rhubarb is not the right one.

[OP2040]

I think I am having some success with Gentian Root.  Without proper tests, these things are always subjective.  Subjectively, I think it has had an effect, but one can never know.  Klotho, or any rh<protein>, seems pretty far out of reach still in terms of cost/access.  It's unfortunate because biologics are very powerful.  The best part about Gentian Root is it's so cheap.  So that's my plan for the foreseeable future when it comes to Klotho. 

[cassioBJJ]

I'll give it a try as well and check my renal blood tests again. As I have renal issues, so it might be easier to find out whether it works or not since Klotho suppose to regenerate kidney.

[JamesPaul]

This site

 

https://mybiohack.co...ics-fat-vitamin

 

lists 8 foods, 13 supplements (including gentian, holy basil, Rhein, Solomon's seal, and a Chinese four-herb combination), 3 probiotics, 5 hormones, 11 drugs/chemicals, and 7 pathways that raise Klotho.

 

It says that there are 3 homologs of Klotho.  Interesting online article.

 

Edited by JamesPaul, 05 April 2019 - 03:12 AM.

[smithx]

A recently published study found that two common drugs taken together at a low dose boosted KLOTHO, among other longevity factors.

 

See this thread: https://www.longecit...an-combination/

 

[rarefried]

I think I am having some success with Gentian Root.  Without proper tests, these things are always subjective.  Subjectively, I think it has had an effect, but one can never know.  Klotho, or any rh<protein>, seems pretty far out of reach still in terms of cost/access.  It's unfortunate because biologics are very powerful.  The best part about Gentian Root is it's so cheap.  So that's my plan for the foreseeable future when it comes to Klotho. 

I plan to experiment with Gentian Root as well (in addition to ursolic acid). 

 

Coincidentally I was about to embark on spermidine supplementation.  I'm holding off for now given its apparent potential to reduce Klotho levels:  

Uremic toxins such as spermidine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (2). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (3).

 

http://www.t3db.ca/toxins/T3D4167