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GDF11 Group buy

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#1 PWAIN

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Posted 21 August 2014 - 09:45 AM


Is anyone interested in organizing a group buy for this? This is such a promising protein. Being a protein, surely we can get some made up. It's $3900 for 1mg on one site, sure we can get it for a LOT less if we buy in bulk. Anyone want to take a lead on this? This could be the big one we've all been waiting for.

 

http://www.newscient...ue#.U_W43IHmeE0

 

....In 2005, Thomas Rando at Stanford University in California and his team found that young blood returned the liver and skeletal stem cells of old mice to a more youthful state during heterochronic parabiosis. The old mice were also able to repair injured muscles as well as young mice...

 

...Spooky things seemed to happen in the opposite direction, too: young mice that received old blood appeared to age prematurely. In some cases, injured muscles did not heal as fast as would be expected.

Several other experiments have shown similar effects. In 2012, Amy Wagers at Harvard University showed that young blood can reverse heart decline in old mice. Her team paired healthy young mice with old mice that had cardiac hypertrophy – a condition which swells the size of their heart – and connected their circulatory systems. After four weeks, the old mouse's heart had shrunk to the same size as its younger partner...

 

Once the researchers had ruled out the effect of reduced blood pressure on the older mice, they identified a protein in the blood plasma called growth differentiation factor 11 (GDF11) that appeared to fall with age. To see if it was linked to the rejuvenating effects, the team gave old mice with enlarged hearts daily injections of GDF11 for 30 days. Their hearts decreased in size almost as much as they had in the parabiosis experiments.

A year later, the same team showed in mice that daily injections of GDF11 also increases the number of blood vessels and the number of stem cells in the brain – both factors known to improve brain function. A separate team led by Tony Wyss-Coray at Stanford performed similar experiments. His team injected blood plasma from young mice into old mice and showed an improvement in the old mice's physical endurance and cognitive function.

In both mice and humans, GDF11 falls with age. We don't know why it declines, but we know it is involved in several mechanisms that control growth. It is also thought to mediate some age-related effects on the brain, in part by activation of another protein that is involved in neuronal growth and long-term memory.

So the billion-dollar question is: would a GDF11 boost have the same effect in humans? Wyss-Coray thinks it will, having taken the next step of injecting young human blood plasma into old mice. His preliminary results suggest that human blood has similar rejuvenating benefits for old mice as young mouse blood does.

"We saw these astounding effects," he says. "The human blood had beneficial effects on every organ we've studied so far."

 

 

 

 


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#2 gt35r

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Posted 21 August 2014 - 07:52 PM

Out of curiosity. What is the expected daily therapeutic dose and how long does the does need to be sustained to achieve results? 

 

Also, is their any pharmacological substitute for GDF-11? Peptides are very expensive to make compared to drugs. Are there any drugs that exist now days that have similar actions as GDF-11?



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#3 pleb

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Posted 21 August 2014 - 08:05 PM

There is another thread about GDF11 I'm not sure where on the site but look for a mention of Sinclair does it again or something like that as a heading Also its produced similarly to insulin using a germ culture in vats and although expensive at this time is likely to drop in price once it becomes better known and the Chinese companies start producing it in bulk.

Edited by pleb, 21 August 2014 - 08:06 PM.

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#4 Logic

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Posted 21 August 2014 - 08:57 PM

I'm confused:

"...GDF11 is a myostatin-homologous protein that acts as an inhibitor of nerve tissue growth. GDF11 has been shown to suppress neurogenesis through a pathway similar to that of myostatin, including stopping the progenitor cell-cycle during G-phase.[3] The similarities between GDF11 and myostatin imply a likelihood that the same regulatory mechanisms are used to control tissue size during both muscular and neural development..."
http://en.wikipedia.org/wiki/GDF11

So do we want more or less of it!??

These guys are selling an antagonist at what looks like a good price:
http://teamtlr.com/t...gdf11&results=1

They also have a presence here:
http://www.longecity...elife-research/

#5 pleb

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Posted 21 August 2014 - 10:28 PM

From memory of Sinclairs article. GDF11 upregulates sirt1-2-3-4-5-6-7 that's about 90 per cent of the body. His article said that in one week it turned a mouse the equivalent of a human of 70 back to the equivalent of a 20 year old. But as its related to myostatin it would presumably be an antagonist of IGF1.
So if your building muscle and using IGF1 you need less but if you want to extend your life or even reverse your age. !!! you need more. At least that's my take on it.

Edited by pleb, 21 August 2014 - 10:32 PM.

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#6 PWAIN

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Posted 21 August 2014 - 11:24 PM

Yes, it is confusing.

 

My take on it is that it acts as a regulator stopping excessive growth where needed and encouraging new growth where needed. Definetly looks like you need to add and not surpress this in the body since the experiments all involve injecting this in the rodents and the level of GDF11 goes down with age. Also they talk about mice with GDF11 gene knocked out having skeletal defects so seems that it is needed for development.

 

I would be interested if anyone has more to add about the apparent contradiction.

 

 

I'm confused:

"...GDF11 is a myostatin-homologous protein that acts as an inhibitor of nerve tissue growth. GDF11 has been shown to suppress neurogenesis through a pathway similar to that of myostatin, including stopping the progenitor cell-cycle during G-phase.[3] The similarities between GDF11 and myostatin imply a likelihood that the same regulatory mechanisms are used to control tissue size during both muscular and neural development..."
http://en.wikipedia.org/wiki/GDF11

So do we want more or less of it!??

These guys are selling an antagonist at what looks like a good price:
http://teamtlr.com/t...gdf11&results=1

They also have a presence here:
http://www.longecity...elife-research/

 


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#7 niner

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Posted 21 August 2014 - 11:53 PM

From memory of Sinclairs article. GDF11 upregulates sirt1-2-3-4-5-6-7 that's about 90 per cent of the body. His article said that in one week it turned a mouse the equivalent of a human of 70 back to the equivalent of a 20 year old. But as its related to myostatin it would presumably be an antagonist of IGF1.
So if your building muscle and using IGF1 you need less but if you want to extend your life or even reverse your age. !!! you need more. At least that's my take on it.

 

You're thinking of NR, not GDF11.


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#8 pleb

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Posted 21 August 2014 - 11:58 PM

Anthropology may provide some of the answer. IGF1 builds muscle. But going back in time when food was in short supply skinny guys had more chance of surviving than guys with muscles.so for the survival of the species as you say down regulating certain hormones like igf1 would help whilst up regulating others would also be of benefit. At that time life expectancy for various reasons was less than 25 years once we were past our breeding age our part in propagating was over so we had reached a point where the necessary hormones to keep us fit for growth and breeding were no longer needed once we were past the stage for the ofspring being able to look after themselves was over we no longer need the hormones that kept us fit through our growth and breeding stage. Then over a period of years the body produced less and less as our job to continue the species was done. this would cover the sirt HGH gdf11 and many others.
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#9 pleb

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Posted 22 August 2014 - 12:09 AM

Hi niner I'm fairly sure it wasn't the nr thread as I wrote Gdf11 down after reading the article. Nr is only mentioned in regard to sirt1 while the gdf 11 thread mentioned sirt1 up to sirt7 I think it said Sinclair strikes again as the heading.it was after the nr thread the only other explanation is that it was on a link from the other posts on gdf

Edited by pleb, 22 August 2014 - 12:14 AM.


#10 PWAIN

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Posted 22 August 2014 - 02:03 AM

Lots of confusion so I asked teamtlr and here is what I got back (posting with permission):

 

What is happening within our current theory is that offsetting homeostatic mechanisms is giving rise to some degree of neurogensis with the pathways fostered by increasing GDF11 expression in 'aged static/homeostatic systems' that will engender the development of neuronal precursors.  However, all the science pre-existing points squarely to antagonist activity or inhibition of GDF11 to be neurogenic as well, and likely more profound, by inducing proliferation of neuronal precursors themselves.   Here is more as follows as relates to all that involves GDF11, GDF8, and NEUMYO-OA.

 

Antagonism of GDF8 and GDF11 are potent stimulators of musculoskeletal regeneration, with GDF11 antagonism being more directed toward the neurological pathways involved.

These are potent anti-aging and 'enhancing' pathways that can drastically counter sarcopoenia, as well as other wasting and cachexic conditions.  Big Pharma has pursued them LESS SUCCESSFULLY than TLR (our agents are well superior, as tested).  Administration does not need to be overly prolonged for highly viable results, therefore does not incur negative modulation of cardiac function or myocardial hypertrophy.

 

One needs to understand that everything that 'grows stuff' has some propensity to do things that are 'not optimal', but such is generally not the case unless markedly 'abused' or overused, and even within that such is questionable here.    Note:  There are no absolute 'free rides' though generally.

ie., Neurogenics grow neurons, etc...and have indication though to foster cancer, diabetes...; as well read up on IGF-1 and it's Growth Factor inherent  'pros and cons', etc...

 

While the recently published Harvard study seems a nice little tidbit of bad science as all evidence points to GDF11 as primarily a negative regulator of neurogenesis and myotrophy.  Did the rules all of a sudden change from all prior studies within the Universe that is Harvard.  Maybe they need funding, LOL.  

 

REAL WORLD research TLR has conducted for over a decade now bears this out.  At best, it is certainly a sub-optimal approach.  Notably NEUMYO-OA is a GDF8-dominant antibody/antagonist, as selectivity is GDF8>GDF11 by a factor of 3.6, which TLR believes may be optimal for musculoskeletal regeneration/rejuvenation/augmentation, and our research has born this out conclusively, even within animals highly challenged for myotrophic/'myo-neurotrophic' outcomes.  Fund us, not Harvard...we have born this out over and over for over a decade   ;) ...note as well, myotrophic/anti-cachexic/anti-sarcopenic research was prior a main focus for TLR and the IP we will release will bear that out.

 

We have developed integrated Optimized Protocols that are astounding within their demonstrated efficacy, and as we know our prior research as well as our future research will bear this out we have no qualms stating such is the case.

 

http://www.ncbi.nlm....es/PMC3011861/ 

 

http://gradworks.umi...77/3577253.html

Quote


Altering muscle hypertrophy and atrophy by suppressing the functions of growth differentiation factors 8 (myostatin) and 11

 

http://www.google.co...s/US20030167492

Comprises growth differentiation factor-11 (GDF-11)/transforming growth factors for modulating muscle cell, bone, kidney and adipose tissue growth in foodstuffs
US 20030167492 A1

Quote


A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-11 (GDF-11) chromosomally integrated into the germ cells of the animal is disclosed. Also disclosed are methods for making such animals, and methods of treating animals, including humans, with antibodies or antisense directed to GDF-11. The animals so treated are characterized by increased muscle tissue and bone tissue.

 

Quote


"...the TGFbeta superfamily ligand GDF11, regulates the genesis of olfactory receptor neurons by inhibiting proliferation of the immediate neuronal precursors (INPs) that give rise to them."

 

Quote


Mice lacking functional GDF11 have more progenitors and neurons in the OE, whereas mice lacking follistatin, a GDF11 antagonist, show dramatically decreased neurogenesis. This negative autoregulatory action of GDF11 is strikingly like that of its homolog, GDF8/myostatin, in skeletal muscle, suggesting that similar strategies establish and maintain proper cell number during neural and muscular development.

 

 


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#11 to age or not to age

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Posted 22 August 2014 - 03:04 AM

this is an edgy move


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#12 tunt01

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Posted 22 August 2014 - 03:57 AM

My interest/curiosity on GDF-11 is very high given the recent data we've seen in the past year.  But I'm wary of the unknown risks.  I wish we had better knowledge of them.



#13 PWAIN

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Posted 22 August 2014 - 05:20 AM

Teamtlr also sent me this (see in italics below). Sounds like we have a potential supplier IF we can get enough interest. I'm going to go ahead and ask for anyone who thinks they may be interested in joining a group buy for GDF11 to post to this thread so we can guage level of interest.

 

 

We have in the past produced both high efficacy antibodies specific to GDF11 itself, as well as the recombinant human GDF11 protein and related proteins, protein-conjugated complexes, modified proteins, and related.  So we have no issues to provide such for progressive research and are willing to do such within a 'sponsored group buy' for anything that might have sufficient interest.

 

We have expertise and vast experience within such and of course guarantee speed of delivery, quality, and so otherwise as would be needed for the most effective means to afford such for progressive research.



#14 pleb

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Posted 22 August 2014 - 08:46 AM

niner was correct that Sinclair strikes again is for NR. but having read through the posts on there that's not the article I had read which was a summary. unfortunately using a kindle means I cannot cut and paste or save links. so I have to try and remember the details of things I have read. at the time I read it i just wrote down the name GDF11. I will try and find the article and post it some other way if I can find it.

Edited by pleb, 22 August 2014 - 08:51 AM.


#15 Logic

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Posted 22 August 2014 - 11:37 AM

I know this topic is about a group buy and is heading way off topic, but feel its important to know whether we want more or less off this protein before proceding.

Hence I have done a site search for GDF11.
If you click on Topic Search to the left on this site and then choose Google site search; you end up with:
http://www.google.co...b=0&gsc.q=gdf11

Note the 2 adds to companies selling GDF11 before the search results for the site show up.

Note the personal trial of NEUMYO-OA GDF-11:
http://www.longecity...personal-trial/

"...Supplements like sodium butyrate and prebiotics like RS and FOS also seem interesting. For sodium butyrate, you can see it go up against drugs like trichostatin A and valproic acid here...
...The last two citations look at "GDNF" not "GDF-11", but since both are influenced by H3 acetylation, this gives an interesting comparison of the effectiveness of various HDAC inhibitors. Sodium butyrate seems to hold up surprisingly well..."

http://www.longecity...-aging-protein/


The confusion seems widespread. Hence the large # of posts on the subject.
It is proven that there is more GDF11 in youngsters and the level drops off as we age.
Now youngsters do tend to stay skinny and then pack on muscle as they mature.

It seems to me that there is a lot of GDF11 while one is growing and building organs and brains.
Then when you have grown, the level drops off and that leads to the more muscle seen from lower levels of GDF11.

This all makes sense until you consider the fact that the levels keep dropping as you age, but in stead of becoming more muscled with age; muscles start to atrophy and the whole theory goes to hell in a hand-basket, along with the conflicting studies!?

Perhaps sudden changes in GDF11 levels cause some sort of signalling cascade which leads to benefits short term until the body reaches equilibrium?

MUCH more study on this subject is required, due to the conflicting studies, IMHO.
Looking at the other substances in young versus old blood would be a good place to start?

Does anyone have any theories as to these conflicting studies while I/we read? {I wish I had more time for this)

Edited by Logic, 22 August 2014 - 11:42 AM.


#16 smithx

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Posted 22 August 2014 - 05:43 PM

Teamtlr seems to sell a lot of small molecule compounds appealing to enthusiasts. They don't look anything like a serious scientific vendor. I doubt they produce any of their own compounds.

 

GDF11 is a complex protein, which can only be produced using recombinant DNA manipulation with a fermentation system, and then quite sophisticated purification. There's no way that this company would have the capability of doing this. They would certainly be outsourcing it to someone.

 

If you want to get something which you are going to inject into your body, I would really recommend going with a very established manufacturer and vendor of similar compounds. There are all sorts of risks involved, from the simple ones of injecting live bacteria to the more subtle ones of getting too much endotoxin or other toxins.

 

Besides the risk that they won't supply the correct protein, or that they will supply the correct polypeptide with the wrong tertiary structure, there is also the risk that what they supply could prove life-threatening because of contamination, impurities, endotoxins, etc.

 

These risks are minimized if you purchase from real scientific suppliers who are already providing the same compound to research labs. Purchasing something this complex from anyone else is a roll of the dice with your own life.

 

 


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#17 gt35r

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Posted 23 August 2014 - 02:56 AM

Agreed. GDF11 will probably require technology that is at least comparable to what it takes to make human insulin. If you don't trust someone to make insulin for you then I would not trust them to make GDF11; I believe GDF-11requires more most translational modification(s) than insulin. 

 

If you have ever been involved in pharmaceuticals or biochemistry you would know how frustrating it is to just purify one protein out of a a tissue, much less cultivating it as well.


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#18 PWAIN

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Posted 23 August 2014 - 04:22 AM

I came across a site where I suspect teamtlr get some of their supplies. It looks like a proper lab supplier and would almost certainly not deal with individuals. They could act to organize the buy and arrange payment and shipping while providing a substantial discount to us due to the large purchase aamount. The quality would likely be the best available and complexity of production would not be something they would be troubled by due to their expertise.

The main issue I can see is that not one person other than myself appears to have expressed interest. Can't have a group buy with just one person...

#19 IpolitBender

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Posted 25 August 2014 - 12:41 PM

I am interested but share the concerns enumerated above.  The tertiary structure is of particular concern.



#20 ramos

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Posted 25 August 2014 - 04:03 PM

Pwain,

 

I am interested in joining the group buy of GDF11.  I am sure more will be interested very soon. 

 

Have you had anymore results from your own tests? 

 

As I have recently joined LongeCity, I am not sure about how we go about this, if you can tell me, I would appreciate it.

 

Ramos 



#21 PWAIN

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Posted 26 August 2014 - 04:33 AM

This looks useful:

 

http://www.sciencedi...09286741300456X

 

Based on these results, we designed a randomized, blinded, vehicle-controlled study to test the effects of rGDF11 on gross and histologic parameters of cardiac hypertrophy. Old (23-month-old) female mice (C57Bl/6) received a daily i.p. injection of rGDF11 (0.1 mg/kg) or saline for 30 days (n = 16 per group). The heart weight-to-tibia length ratio was significantly lower in old mice injected with rGDF11 compared to the saline-injected control group (Figure 7D). Morphometric analysis further demonstrated that rGDF11 treatment resulted in significantly smaller cardiomyocytes compared to saline-injected controls (Figure 7E).

We also investigated molecular changes in the hearts of rGDF11-treated aged mice. We detected a significant reduction in BNP and a similar trend in ANP, both molecular markers associated with cardiac hypertrophy ( Figure 7F). Conversely, SERCA-2 transcript levels, which correlate with diastolic function ( Dai et al., 2009), were increased in rGDF11-treated hearts relative to saline-treated age-matched controls. This pattern of rGDF11-induced decrease in molecular markers of hypertrophy and increase in SERCA-2 expression resembles the pattern observed in old mice exposed to a young circulation by parabiosis. We also performed echocardiographic evaluation of 24-month-old male C56Bl/6 mice that were randomized to receive a daily i.p. injection of rGDF11 (0.1 mg/kg) or vehicle for 30 days. None of the functional parameters we evaluated was significantly different between the two groups ( Table S2).

GDF11 Does Not Prevent Cardiac Hypertrophy after Pressure Overload In Vivo

To determine if the effect of GDF11 on cardiomyocytes is specific for age-related cardiac hypertrophy, 2-month-old female C56Bl/6 mice were subjected to transverse aortic constriction and then randomized to receive a daily i.p. injection of rGDF11 (0.1 mg/kg) or vehicle for 30 days. We performed an echocardiographic evaluation at 15 days and then prior to sacrifice (Figure S6C). After 30 days, mice were euthanized, and hearts were collected for histological and molecular evaluation. We evaluated cardiac morphometry by measuring the heart weight-to-tibia length ratio: there was no significant reduction in hypertrophy in mice subjected to aortic banding and treated for 30 days with rGDF11 (n = 10) as compared with hearts of mice that received only vehicle (n = 9) (p = 0.4; Figure S6A). Furthermore, cardiomyocyte cross-sectional area was not significantly different (Figure S6B). We also evaluated development of cardiac fibrosis and did not detect any difference between the two groups (data not shown). These data suggest that GDF11 does not prevent all forms of cardiac hypertrophy.



#22 Bryan_S

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Posted 03 September 2014 - 05:58 AM

I'm interested as well but the price is a show stopper. Do we have any data on what the natural levels are in a young human body and can we extrapolate a realistic dose from that data? I just ran the numbers, if I use the (0.1 mg/kg) example this will cost a fortune at over 8 mg per day. Also what would an appropriate treatment length run 4-8 weeks, has anyone worked all this out, remember we aren't mice? Once we know the basics we can extrapolate how much each person will need over a given treatment length and see how many of us will need to get involved to make this affordable.



#23 poonja

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Posted 11 September 2014 - 11:21 AM

Fascinating protein.  Particularly for a 67 year old man.  I will keep checking back to see if this project gets off the ground.



#24 Bryan_S

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Posted 28 September 2014 - 06:45 PM

FYI

 

http://www.longecity...an/#entry690080

 

A small trial of less than 20 Alzheimer’s patients, conducted at Stanford will begin in a few days. It is privately funded by Alkahest, Inc.



#25 mpe

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Posted 29 September 2014 - 02:20 AM

The trial is on young blood serum which contains gdf-11, not just gdf-11. The results of the trial could say a lot about young blood serum, but very little about gdf-11.

 

Mike



#26 tunt01

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Posted 29 September 2014 - 03:39 AM

I'm interested as well but the price is a show stopper. Do we have any data on what the natural levels are in a young human body and can we extrapolate a realistic dose from that data? I just ran the numbers, if I use the (0.1 mg/kg) example this will cost a fortune at over 8 mg per day.

 

 

You cannot extrapolate the data directly, because it is mice, which have a different metabolism than humans.  The conversion is approximately 0.0081 mg/kg in Humans.  For a 60 kg human it is approximately 0.5 mg per day.



#27 Bryan_S

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Posted 29 September 2014 - 08:07 AM

Its Tony Wyss-Coray of Stanford and yes it's not just testing only GDF11, he said that much already. This study was the easiest way to test the data from Wagner and his earlier findings on mice concerning GDF11. If you have any doubts look up Alkahest, Inc and GDF11, they are looking to find ways to stimulate and produce the correct GDF factors (they think GFD11 is just one of many) but they need positive clinical data to support the next phase of research.



#28 Logic

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Posted 06 November 2014 - 08:54 PM

GHK was discovered during studies comparing the effect of human plasma from young persons (age 20–25) to plasma from older persons just like GDF11 was and should synergise well with GDF11.

The research says it repairs DNA and just about everything else too.
I want to get a group buy going for this stuff and thought people here might be interested.

http://www.longecity...c-regeneration/
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#29 Bryan_S

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Posted 13 November 2014 - 08:15 PM

Interesting appearance on amazon.

 

31AUVmMwwLL.jpg

 

 

http://www.amazon.co...CFXIV7Aod81sAgQ

 

Took a look at the companies website and they do offer GDF-11 http://www.raybiotec...-gdf-11-en.html

 

 

Recombinant Human GDF-11

CODE: 213-10127-2

$190.00

 
Recombinant Human GDF-11 (20ug)
 
Anyone priced anything better? Looks like they are reaching out to the public if it's appearing on Amazon.

 


Edited by Bryan_S, 13 November 2014 - 08:19 PM.


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#30 relativityboy

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Posted 22 February 2015 - 02:26 AM

It's down to $75. I'm surprised they're offering it at all. With it being one 200th? of a gram that's not much to play with.







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