52 replies to this topic

[YOLF]

PEP-1192 raises klotho and it stands to reason that it can sustainably regenerate kidneys in humans as it does in rodents. Klotho is produced in the kidneys where it is also required to sustain the form and function of kidneys. For aging, increasing klotho levels would be expected to produce permanent (still subject to aging) results. Most patients who find themselves needing a kidney don't get it. Research into this compound could greatly reduce the burden and offer a great deal of hope to patients.

 

FGF1 is relatively research limited, but it can sustainably reverse Type II diabetes in rodents via mechanisms which are likely to be conserved between species. Diabetes is an underlying cause for many with kidney problems. FGF1 stands for Fibroblast Growth Factor 1, fibroblasts are a type of stem cell that synthesize the extracellular matrix and produce collagen. It stands to reason that FGF1 may activate mechanisms for the removal of extracellular junk (SENS). It should also produce interesting and positive results in patients or rodents with connective tissue disorders (certain types of joint pain).

 

Together, these compounds could lead to sustained systemic regeneration and restored youth.

 

More details will follow. I'm time limited right now.

[onemanatatime]

Thanks for the invite . 

[ceridwen]

Very interested. Can this get through the blood brain barrier?

[PWAIN]

Dose and cost are pretty important in any group buy.

[Robert Seitz]

I'm also interested in participating.

 

[Ark]

Count me in, thanks!

[YOLF]

Very interested. Can this get through the blood brain barrier?

I don't see why it wouldn't. Either way, if it regenerates other parts of your body as well as might be expected from the papers, that will have a definite improvement on brain health.

 

Plasma Klotho and Cognitive Decline in Older Adults: Findings From the InCHIANTI Study.

 

 

RESULTS:

Each additional natural logarithm of klotho (pg/mL) was associated with 35% lower risk of meaningful decline in MMSE, defined as decline exceeding three points (relative risk = 0.65; 95% confidence interval 0.45, 0.95; p value = .02), and 0.75-point smaller average 3-year decline (baseline to 3-year visit) in MMSE (95% confidence interval 0.02, 1.48; p value = .04). No statistically significant associations were found between klotho and declining Trails A (relative risk = 0.99; 95% confidence interval 0.75, 1.32; p value = .97) and B (relative risk = 1.02; 95% confidence interval 0.84, 1.24; p value = .82).

CONCLUSIONS:

Higher plasma klotho concentrations were associated with lower risk of meaningful decline and smaller average decline in MMSE. We did not observe such findings with Trails A and B, perhaps because they test executive function and motor skills, whereas MMSE measures global cognition. Future studies should investigate mechanisms through which klotho may affect domain-specific cognitive changes.

 

More, and lots more to read on this on PubMed:

Klotho Is a Neuroprotective and Cognition-Enhancing Protein.

[YOLF]

So far, I'm able to get ALT-711/Alagebrium. 50g will be $125 including expedited mail in the US. Human dosing was between 200mg and up to around 350mg iirc. 

 

Alagebrium  

 

 

However, treatment with alagebrium in diabetic RAGE apoE KO mice reduced renal AGE levels and further reduced glomerular matrix accumulation. In addition, even in the absence of RAGE expression, alagebrium attenuated cortical inflammation... https://www.ncbi.nlm...les/PMC3402321/

 

I've also talked with others who found it useful and effective. The difference between performance in cardiovascular diseases in humans and in rodents is likely to be the rate of cellular turnover or rate of ECM remodelling which can be enhanced by alpha hydroxy acids such as malic acid, pyruvic acid, potentially FGF1, cosmetic peptides, stem cell proliferation, and growth. If anyone is on HGH or is getting regular stem cell treatments of any kind, I'd love to see some before and after skin pics.

 

See also:

academic.oup.com/ndt/article/26/11/3474/1831400/Renoprotective-antioxidant-effect-of-alagebrium-in

http://www.kidney-in...2552-0/fulltext

[Rocket]

I am in if it isn't ridiculously expensive.

[BobSeitz]

I, too.

 

[YOLF]

Very promising charts for alagebrium on page SS7:

Role of the AGE Crosslink Breaker Alagebrium:

http://www.kidney-in...(15)52552-0/pdf

 

One thing to keep in mind though, not all of the effects of alagebrium translate to humans, but those that don't should be seen as potential, not as failures, it just means we have to co-administer them with adjuvants to achieve those ends.

 

[YOLF]

Alright, so here's some more intel on PEP1192:

Klotho is actually involved in fibroblast growth factor receptor binding. That is, you have FGFs floating around in your blood stream, and klotho is the receptor that allows your cells to use it. So delivering it to your cells, helps deliver FGFs to their target cells. There are implications that Klotho and FGFs mediate cellular turnover of ECM components and help to determine the form, and thus function of cells and allow for the removal of glycation from ECM. Some of this will be excreted by the kidneys and liver, though some of it will redeposit, and that's where age breakers come in. In rodents, we know that the rate of cellular turnover, and by virtue of this, ECM turnover, alagebrium is very effective as an age breaker. So I'd expect alagebrium, PEP1192, and FGF1 to be a rejuvenation trifecta. Here is a good all in one place reference for this information.

 

The more I think about it, the more I realize how important alagebrium is going to be to this process. We know that where enough Klotho can be protected by tocotrienols, we can reverse plaque diseases and even restore kidney function. In my opinion, these are going to be the kinds of drugs which mark the turning point on the war against aging and death and save alot of lives by default. 

 

Another thought I'm having is that Klotho will be more crucial than FGF1 as cancers can use FGF1 to carve out space for themselves. So first having adequate Klotho (PEP1192) and age breaking capacity (alagebrium... AGEs are responsible for cancer development) will be of great importance, otherwise we may not get enough of the FGF1 to where it is necessary to achieve the results we want. Similarly, we can take all the alagebrium we want, but if we aren't creating ECM turnover, we're not gaining an opportunity to remove glucosepane and other AGEs. It may be better if I make these three available as a package to avoid misuse. Alagebrium is the easiest to get, the others are proving more difficult. But I do know of at least one possible alternative to Klotho (well, maybe) which is readily available and the combination of it and alagebrium should be sufficient to restore more youthful metabolism of our endogenous FGFs. One way or another, we'll get this done!

Edited by YOLF, 13 September 2017 - 04:56 AM.

[cassioBJJ]

I am interested too. Have you guys been able to buy this?

[YOLF]

How much interest is there in this group buy? I can likely get PEP1192 and FGF1 if we have enough interest to get a nice bulk discount.

 

I've heard conflicting opinions on Alagebrium... that one is up in the air, though pentosidine is my new favorite AGE target rather than glucosepane, and breaking any AGE will be to our benefit to some degree, especially if we're able to mobilize more of it. In any case, we can make it work. The Alagebrium would be $200 + Shipping per 150 days worth of dosing for powder and I'd need to sell at least 30.

 

What's everyone willing to spend?

[Robert Seitz]

What do you think the package might cost?

 

 

[poonja]

I also am interested in participating.

[Nate-2004]

I'd be interested in PEP-1192 if it's not super expensive. Also FGF.  

 

I'm not so sure about ALT-711, that is not an effective drug in humans. It does nothing to break glucosepane crosslinks.

[YOLF]

I'd be interested in PEP-1192 if it's not super expensive. Also FGF.  

 

I'm not so sure about ALT-711, that is not an effective drug in humans. It does nothing to break glucosepane crosslinks.

There's other stuff to break besides glucosepane and we'll find out what SENS has discovered soon enough.

 

You had mentioned pentosidine in another thread. I'm still somewhat unfamiliar with it, but I think personally, I might be just as concerned if not more concerned with eliminating that if it's what's making my skin look old. It would be a pity if we didn't figure out what the benefits that kidney patients see from taking alagebrium are coming from. I'm definitely interested in preserving the health of the most irreplaceable organ in my body. 

 

Anyways, this combination changes up the game and adds a new layer of solution that could deliver glucosepane to the alagebrium molecule, so we don't know if alagebrium doesn't work under these circumstances. FGF1 and Klotho influence cellular turnover, and that is a major difference between us and the rodents that this had success in. Many of us might still have somewhat higher cellular turnover rates also being that we are younger than the other test groups. I feel like you keep missing the complexity of things here...

What do you think the package might cost?

 

I'll have to get back to you on this, I had alot of dead ends trying to get this stuff and I'll need to reorganize my search for the FGF1 and Klotho. 

[ceridwen]

Can Klotho get through the blood brain barrier?

[YOLF]

Can Klotho get through the blood brain barrier?

It's possible and probable considering those with higher levels have higher levels of cognition.

[cassioBJJ]

YOLF,

 

Do you have an estimation of costs and dosage for PEP1192 and FGF1 ?

 

Thanks

[YOLF]

YOLF,

 

Do you have an estimation of costs and dosage for PEP1192 and FGF1 ?

 

Thanks

I hope to get estimates some time this week.

[cassioBJJ]

Hello YOLF, did you have any news about the estimates?

[YOLF]

It looks like I've taken on too much lately. Give me another week or two.

[cassioBJJ]

It looks like I've taken on too much lately. Give me another week or two.

 

 

Hey YOLF,

 

Did you manage to get any the peptide?

 

Thank you
 

[YOLF]

Found it(FGF1), but I'm going to need more buyers to get the price down. At present it's as much as $190,000/year, but could make it down to $1000 with recombinant scaling. The single shot to reverse diabetes would be around $500 and you'd have to inject it into your head or get a qualified medical professional to do it for you.

 

On the positive side, there are inexpensive receptors to increase uptake, so we can circumnavigate multiple expensive peptides.

 

They also found that FGF! can increase adipogenesis, so it'll have to be taken with something that can abolish or redirect that effect. I'm working on some ideas there, it's not impossible and the adipogenesis might be of the kind that gives you a face lift. I need to do some more reading, I've found alot of new material.

[cassioBJJ]

Found it(FGF1), but I'm going to need more buyers to get the price down. At present it's as much as $190,000/year, but could make it down to $1000 with recombinant scaling. The single shot to reverse diabetes would be around $500 and you'd have to inject it into your head or get a qualified medical professional to do it for you.

 

On the positive side, there are inexpensive receptors to increase uptake, so we can circumnavigate multiple expensive peptides.

 

They also found that FGF! can increase adipogenesis, so it'll have to be taken with something that can abolish or redirect that effect. I'm working on some ideas there, it's not impossible and the adipogenesis might be of the kind that gives you a face lift. I need to do some more reading, I've found alot of new material.

 

What about the PEP-1192? Did you manage to get the price of this one?

 

Thanks!

[OP2040]

I am also interested in the PEP-1192.  I don't see a lot of research on this particular segment of Klotho.  But I'd be in for a group buy after seeing some results from other users.  I suppose that would be a 2nd round group buy.

[OP2040]

Found it(FGF1), but I'm going to need more buyers to get the price down. At present it's as much as $190,000/year, but could make it down to $1000 with recombinant scaling. The single shot to reverse diabetes would be around $500 and you'd have to inject it into your head or get a qualified medical professional to do it for you.

 

On the positive side, there are inexpensive receptors to increase uptake, so we can circumnavigate multiple expensive peptides.

 

They also found that FGF! can increase adipogenesis, so it'll have to be taken with something that can abolish or redirect that effect. I'm working on some ideas there, it's not impossible and the adipogenesis might be of the kind that gives you a face lift. I need to do some more reading, I've found alot of new material.

 

I think you may be trying to do too much.  Can we just move forward with Klotho?  We have plenty of people interested, so probably enough to get the price break.

 

If we can get folks to make a commitment, then we can move the discussion on to important issues like delivery and storage.  The FOX04-dri thread would be a great model to follow as it has been pretty successful.

 

One question I have is whether one treatment with Klotho or FGF1 has been shown to be enough to cause reversal of disease states?  If it is the equivalent of a series of treatments in mice, then it is likely going to be too expensive for most people.

[YOLF]

The idea is that the price will come down as it does with anything when people use it if there is success after using it. Then someone will order metric tons of it and it'll come in a bottle.

 

I can tell you now, that I'm using an improvised complex that isn't all that dissimilar from the complex I've posted here with great success and I feel that if I can get purer materials to work with it could go much further. I definitely miss it when I stop taking it, but I'm swallowing alot more stuff to get a small quantity of similar molecules. 

 

If I didn't mention it already, heparin is potentially a replacement for klotho as it acts as receptor for it. So as long as we can get a good deal on some FGF, I think we'll be in good shape.