217 replies to this topic

[Logic]

Why not increase your own production of GDF-11 with HDAC inhibitors like sodium butyrate and prebiotics like RS and FOS and medium chain triglycerides for a start?

http://www.longecity...ndpost&p=662013

http://www.longecity...rs/#entry698831

Also; would it not be a good idea to raise other factors that are higher in young blood at the same time, like GHK?
http://www.longecity...c-regeneration/

Edited by Logic, 29 January 2015 - 02:14 PM.

[pone11]

Why not increase your own production of GDF-11 with HDAC inhibitors like sodium butyrate and prebiotics like RS and FOS and medium chain triglycerides for a start?

http://www.longecity...ndpost&p=662013

http://www.longecity...rs/#entry698831

Also; would it not be a good idea to raise other factors that are higher in young blood at the same time, like GHK?
http://www.longecity...c-regeneration/

 

Can anyone quantify how do the elevated levels of GDF11 seen with tributyrin compare against the therapeutic injected doses of GDF11 used in the mouse studies?

 

The mouse studies used high doses of GDF11 daily.  I wonder if the effects seen through HDAC inhibitors is really giving a comparable dose?

[Logic]

Can anyone quantify how do the elevated levels of GDF11 seen with tributyrin compare against the therapeutic injected doses of GDF11 used in the mouse studies?
 
The mouse studies used high doses of GDF11 daily.  I wonder if the effects seen through HDAC inhibitors is really giving a comparable dose?

A good question as GDF-11 is so hellishly expensive.
I hope someone qualified chimes in.
Also where to get Tributyrin or Sodium Butyrate?
Others??

It looks like MCT Oil or Virgin Coconut Oil will increase Tributyrin levels and is easily available:
http://www.longecity...ndpost&p=666451

A good place to start would be Fructooligosaccharides (FOS) and Resistant starch (RS) as these are so cheap that it doesn't matter if GDF-11 the levels aren't much higher.
http://en.wikipedia....esistant_starch
http://en.wikipedia....oligosaccharide

(I need to scour the forum for anecdotal reports again as they may shed some light on the question, but do remember gas being a problem )


 

[pone11]

 

Can anyone quantify how do the elevated levels of GDF11 seen with tributyrin compare against the therapeutic injected doses of GDF11 used in the mouse studies?
 
The mouse studies used high doses of GDF11 daily.  I wonder if the effects seen through HDAC inhibitors is really giving a comparable dose?

A good question as GDF-11 is so hellishly expensive.
I hope someone qualified chimes in.
Also where to get Tributyrin or Sodium Butyrate?
Others??

It looks like MCT Oil or Virgin Coconut Oil will increase Tributyrin levels and is easily available:
http://www.longecity...ndpost&p=666451

A good place to start would be Fructooligosaccharides (FOS) and Resistant starch (RS) as these are so cheap that it doesn't matter if GDF-11 the levels aren't much higher.
http://en.wikipedia....esistant_starch
http://en.wikipedia....oligosaccharide

(I need to scour the forum for anecdotal reports again as they may shed some light on the question, but do remember gas being a problem )
 

 

Sodium butyrate is here:

http://www.amazon.co...s/dp/B0058A9SF0

 

I get lots of gas and diarrhea taking it, so for anyone with IBS or similar conditions be careful.   It would be interesting to see if Tributyrin absorbs differently.

 

I would not compare FOS to RS.   Resistant starch is a primary fuel source for bad bacteria, and while it does produce a lot of butyrate from fermentation in the gut, it also fails to meet good endpoints for fasting and postpandrial glucose in human trials.   There are good articles on this on the Animal Pharm blog (a blog specializing in gut bacteria issues).    The concern is that raw potato starch and other high-dose resistant starches may be giving a fuel source to bacteria in inappropriate places (small intestine) as well as the wrong types of bacteria.

 

To contrast, FOS, psyllium, acacia, inulin and similar fibers are primary fuels for good bacteria species and would be a much preferred fiber source.   

 

I know many people love taking potato starch and these points are still controversial among that audience.

[Logic]

Sodium butyrate is here:

http://www.amazon.co...s/dp/B0058A9SF0

 

I get lots of gas and diarrhea taking it, so for anyone with IBS or similar conditions be careful.   It would be interesting to see if Tributyrin absorbs differently.

 

I would not compare FOS to RS.   Resistant starch is a primary fuel source for bad bacteria, and while it does produce a lot of butyrate from fermentation in the gut, it also fails to meet good endpoints for fasting and postpandrial glucose in human trials.   There are good articles on this on the Animal Pharm blog (a blog specializing in gut bacteria issues).    The concern is that raw potato starch and other high-dose resistant starches may be giving a fuel source to bacteria in inappropriate places (small intestine) as well as the wrong types of bacteria.

 

To contrast, FOS, psyllium, acacia, inulin and similar fibers are primary fuels for good bacteria species and would be a much preferred fiber source.   

 

I know many people love taking potato starch and these points are still controversial among that audience.

 

 

Thx for the link and heads up on RS Pone11.

More research reqd.  sigh!
 

[pone11]

 

Sodium butyrate is here:

http://www.amazon.co...s/dp/B0058A9SF0

 

I get lots of gas and diarrhea taking it, so for anyone with IBS or similar conditions be careful.   It would be interesting to see if Tributyrin absorbs differently.

 

I would not compare FOS to RS.   Resistant starch is a primary fuel source for bad bacteria, and while it does produce a lot of butyrate from fermentation in the gut, it also fails to meet good endpoints for fasting and postpandrial glucose in human trials.   There are good articles on this on the Animal Pharm blog (a blog specializing in gut bacteria issues).    The concern is that raw potato starch and other high-dose resistant starches may be giving a fuel source to bacteria in inappropriate places (small intestine) as well as the wrong types of bacteria.

 

To contrast, FOS, psyllium, acacia, inulin and similar fibers are primary fuels for good bacteria species and would be a much preferred fiber source.   

 

I know many people love taking potato starch and these points are still controversial among that audience.

 

 

Thx for the link and heads up on RS Pone11.

More research reqd.  sigh!
 

 

 

The psyllium, acacia, and inulin are all available from NOW Foods on Amazon, and I find them all really well tolerated.  They are used by many beneficial species like B Longum that get very depleted on high starch diets, so I think there is little harm in doing 1 teaspoon of each of those three each day.

 

I kind of doubt that any form of starch is going to magically create enough GDF11 to reverse aging.  That's pure speculation.

 

Edited by pone11, 30 January 2015 - 11:00 PM.

[Logic]

The psyllium, acacia, and inulin are all available from NOW Foods on Amazon, and I find them all really well tolerated.  They are used by many beneficial species like B Longum that get very depleted on high starch diets, so I think there is little harm in doing 1 teaspoon of each of those three each day.
 
I kind of doubt that any form of starch is going to magically create enough GDF11 to reverse aging.  That's pure speculation.

Thx.

Getting the gut to produce butyrate certainly isn't going to reverse aging.
If it did all sorts of apes and other animals with diets high in these things would be... 'immortal'.
They, external sources of butyrate and other HDAC inhibitors are a start though, until an affordable source of GDF-11 comes along.

[xEva]

Why not increase your own production of GDF-11 with HDAC inhibitors like sodium butyrate and prebiotics like RS and FOS and medium chain triglycerides for a start?

I remembe first coming across sodium butyrate in an old Richard Veech article on ketones. At the time (~12 years ago) it was hoped that supplementing it could mimic the beneficial results of a fast, because it is supposed to metabolize into beta-hydroxybutyrate (β-OHB or βHB), the main ketone. But then it turned out that one could not take substantial quantities of it without developing some problems, one being sodium overload.

But! if you have reasons to believe that sodium butyrate will elevate GDF11 levels --and I presume you give them in the links, which I have not looked at yet-- then a prolonged fast should do it infinitely cheaper, since βHB levels reach 5-7 mMol/L by 14-17th day of a water-only fast.

Edited by xEva, 31 January 2015 - 04:05 AM.

[Bryan_S]

I would be willing to put a GDF11 group buy together "if" we knew more about the dosage and the size of the interest.

 

We can also wait and see if the Boston researchers come up with a drug to promote the body to produce more GDF11.

 

On the flip side:

If someone knows about setting up recombinant protein expression systems I've already found some Human GDF11 plasmids we can order. Its not like the elements to set this up are really hard to come by. The plasmids themselves can also be custom engineered if something specific is needed in the production process not already contained within the cataloged plasmids. 

 

Now there is third way to raise GDF11 levels, one not mentioned or tested before. Some of us talk about how someone needs to take an altruistic path and do something good for mankind, well here it is. This would be truly controversial because once done the protein would be self replicating and no pharmaceutical company could ever control it. As one would imagine certain safeguards would also need to be implemented, at least in the beginning until all interactions are known. As you would want the ability to stop the production of GDF11 and if need be shut down totally and absolutely if necessary. It would take a probiotic path and a group of modified bacteria could permit controlled release of GDF11 into the gut of the human body for absorption.

 

We are already finding that our gut bacteria benefits the production of many hormones and vitamins. See Table 1 The acidic conditions of the stomach rapidly diminish further down the intestinal tract where products produced by your intestinal flora remain intact. Its only a matter of time before someone engineers bacteria to produce the drugs we need. With the before mentioned safeguards scientists have already created a bacteria that thrives in the laboratory, growing robustly as long as an unnatural amino acid is included in their diet.

 

Soon a new dawn will appear allowing the testing of Genetically modified bacteria within our own bodies. Some of us are already thinking about the applications for certain natural substances needed by the human body that shouldn't be controlled by the pharmaceutical companies.

Edited by Bryan_S, 03 February 2015 - 01:58 AM.

[pone11]

 

Why not increase your own production of GDF-11 with HDAC inhibitors like sodium butyrate and prebiotics like RS and FOS and medium chain triglycerides for a start?

I remembe first coming across sodium butyrate in an old Richard Veech article on ketones. At the time (~12 years ago) it was hoped that supplementing it could mimic the beneficial results of a fast, because it is supposed to metabolize into beta-hydroxybutyrate (β-OHB or βHB), the main ketone. But then it turned out that one could not take substantial quantities of it without developing some problems, one being sodium overload.

But! if you have reasons to believe that sodium butyrate will elevate GDF11 levels --and I presume you give them in the links, which I have not looked at yet-- then a prolonged fast should do it infinitely cheaper, since βHB levels reach 5-7 mMol/L by 14-17th day of a water-only fast.

 

 

There is research literature suggesting patients in ketosis need supplemental sodium, and many in ketosis are supplementing up to 5 grams of sodium per day (pretty high doses).

 

My sodium-potassium butyrate supplement from BodyBio has a measly 70 mg of sodium and 100 mg of potassium for every 500 mg of butyric acid.  That's hardly the stuff of sodium overloads, particularly in light of how ketogenic diets usually require higher sodium.

 

The problem I have with the butyrate supplements is gas and loose bowel.  My body seems to want to flush it out as quickly as possible.

[Logic]

...Now there is third way to raise GDF11 levels, one not mentioned or tested before. Some of us talk about how someone needs to take an altruistic path and do something good for mankind, well here it is. This would be truly controversial because once done the protein would be self replicating and no pharmaceutical company could ever control it. As one would imagine certain safeguards would also need to be implemented, at least in the beginning until all interactions are known. As you would want the ability to stop the production of GDF11 and if need be shut down totally and absolutely if necessary. It would take a probiotic path and a group of modified bacteria could permit controlled release of GDF11 into the gut of the human body for absorption.
 
We are already finding that our gut bacteria benefits the production of many hormones and vitamins. See Table 1 The acidic conditions of the stomach rapidly diminish further down the intestinal tract where products produced by your intestinal flora remain intact. Its only a matter of time before someone engineers bacteria to produce the drugs we need. With the before mentioned safeguards scientists have already created a bacteria that thrives in the laboratory, growing robustly as long as an unnatural amino acid is included in their diet.
 
Soon a new dawn will appear allowing the testing of Genetically modified bacteria within our own bodies. Some of us are already thinking about the applications for certain natural substances needed by the human body that shouldn't be controlled by the pharmaceutical companies.

 

We may not be able to agree on Niacin, Nicotinamide and Nicotinamide Riboside Bryan but here we do. 
 
The are ten gut bacteria fo every cell that makes up our body and they are all excreting the substances we live on.
Put another way:  We all live on bacteria shit... (sung to the tune of Yellow Submarine) 
That being the case;  its a damn good idea to make sure we approve of what the bacteria are excreting and hence said bacteria!
 
While GM  bacteria are a thing of the future and I worry about who will own the synthetic amino's used to control them and hence us,  there are countless natural bacteria science is unaware of.
Here are some butyrate producing bacteria science has recently become aware of:
 

"...Here, we demonstrate that the administration of a probiotic, VSL#3, prevented and treated obesity and diabetes in several mouse models. VSL#3 suppressed body weight gain and insulin resistance via modulation of the gut flora composition. VSL#3 promoted the release of the hormone GLP-1, resulting in reduced food intake and improved glucose tolerance. The VSL#3-induced changes were associated with an increase in the levels of a short chain fatty acid (SCFA), butyrate. Using a cell culture system, we demonstrate that butyrate stimulated the release of GLP-1 from intestinal L-cells, thereby providing a plausible mechanism for VSL#3 action..."
http://www.ncbi.nlm....pubmed/23836895

It has been shown that lactic acid, produced in vitro by lactic acid bacteria, is used by some strictly anaerobic butyrate-producing bacteria of clostridial cluster XIVa for the production of high concentrations of butyric acid...
...a synbiotic approach, using a prebiotic in combination with a butyrate producer, may help to re-establish such bacteria in the individual in the diseased state. First attempts have been made in animal models of IBD to apply butyrate-producing bacteria (Sokol et al., 2008; Eeckhaut et al., 2009). Strains of clostridium cluster IV and XIVa were found to be highly successful in decreasing inflammation and necrosis in rodent IBD models. Indeed, Faecalibacterium prausnitzii, a species belonging to cluster IV, has been shown to be much less prevalent in the gut microbiota of IBD patients.
http://jmm.sgmjourna...t/59/2/141.full

 
Note the references in the last link. Here are some:
 

The anaerobic butyrate-producing strain Butyricicoccus pullicaecorum decreases colonic inflammation and ulceration in a TNBS-induced colitis rat model.
http://www.probiotic...ics_Newfood.pdf

Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine.
http://jmm.sgmjourna...e&resid=294/1/1

In summary:
It may be possible to boost Butyrate - GDF-11 considerably with the right probiotic/s initially and then daily intake of the right prebiotics/fibre.
Doing so is going to take some research on our part however.
 
In the mean time; Tributyrin seems to be the way to go?
http://www.thedcasit...m/Butyrate.html

[Logic]

"...Butyrivibrio fibrisolvens, a butyrate-producing ruminal bacterium, was evaluated for use as a probiotic to prevent colorectal cancer. Oral administration to Jcl:ICR mice of a new strain of B. fibrisolvens (MDT-1) that produces butyrate at a high rate (109 cfu/dose) increased the rate of butyrate production by fecal microbes, suggesting that MDT-1 can grow in the gut..."
http://jn.nutrition....35/12/2878.full

[pone11]

 

It may be possible to boost Butyrate - GDF-11 considerably with the right probiotic/s initially and then daily intake of the right prebiotics/fibre.
Doing so is going to take some research on our part however.
 

 

Does anyone know of a commercial lab that measures GDF-11 in plasma or whole blood?    Without that, how could you even begin to test the effect of other nutrients on your GDF11 levels? 

[Logic]

It may be possible to boost Butyrate - GDF-11 considerably with the right probiotic/s initially and then daily intake of the right prebiotics/fibre.
Doing so is going to take some research on our part however.

 
Does anyone know of a commercial lab that measures GDF-11 in plasma or whole blood?    Without that, how could you even begin to test the effect of other nutrients on your GDF11 levels?

Good point Pone11. the thought didn't cross my mind.
I suppose we could go on anecdotal evidence and see if we get the same results as the studies, but a means to test would be the answer.

[xEva]

I remembe first coming across sodium butyrate in an old Richard Veech article on ketones. At the time (~12 years ago) it was hoped that supplementing it could mimic the beneficial results of a fast, because it is supposed to metabolize into beta-hydroxybutyrate (β-OHB or βHB), the main ketone. But then it turned out that one could not take substantial quantities of it without developing some problems, one being sodium overload.

There is research literature suggesting patients in ketosis need supplemental sodium, and many in ketosis are supplementing up to 5 grams of sodium per day (pretty high doses).
 
My sodium-potassium butyrate supplement from BodyBio has a measly 70 mg of sodium and 100 mg of potassium for every 500 mg of butyric acid.  That's hardly the stuff of sodium overloads, particularly in light of how ketogenic diets usually require higher sodium.
 
The problem I have with the butyrate supplements is gas and loose bowel.  My body seems to want to flush it out as quickly as possible.

Veech was speaking about the amount of sodium butyrate necessary to reach the therapeutic dose of βHB that would mimic a fast. Here is quote:

As an organic acid, βOHB is soluble as the sodium salt. A fasting adult produces about 150 grams daily to achieve a blood level of 5-8 mM. If this amount of βOHB were administered as the sodium salt, a large residual excess of alkali would remain as the βOHB is metabolized.
Cahill, Veech, Ketoacids? Good Medicine? 2003 http://okdentalwelln...3-Superfuel.pdf

So, if we take the data you give "70 mg of sodium and 100 mg of potassium for every 500 mg of butyric acid", the target 150g of butyric acid will result in 21g of sodium and 30g of potassium -ouch!

But how much of the stuff you take? The symptoms you describe are consistent with sodium overdose (like in a 'saline purge' == lotsa salt + water)

[pone11]

 

 

I remembe first coming across sodium butyrate in an old Richard Veech article on ketones. At the time (~12 years ago) it was hoped that supplementing it could mimic the beneficial results of a fast, because it is supposed to metabolize into beta-hydroxybutyrate (β-OHB or βHB), the main ketone. But then it turned out that one could not take substantial quantities of it without developing some problems, one being sodium overload.

There is research literature suggesting patients in ketosis need supplemental sodium, and many in ketosis are supplementing up to 5 grams of sodium per day (pretty high doses).
 
My sodium-potassium butyrate supplement from BodyBio has a measly 70 mg of sodium and 100 mg of potassium for every 500 mg of butyric acid.  That's hardly the stuff of sodium overloads, particularly in light of how ketogenic diets usually require higher sodium.
 
The problem I have with the butyrate supplements is gas and loose bowel.  My body seems to want to flush it out as quickly as possible.

 

Veech was speaking about the amount of sodium butyrate necessary to reach the therapeutic dose of βHB that would mimic a fast. Here is quote:

As an organic acid, βOHB is soluble as the sodium salt. A fasting adult produces about 150 grams daily to achieve a blood level of 5-8 mM. If this amount of βOHB were administered as the sodium salt, a large residual excess of alkali would remain as the βOHB is metabolized.
Cahill, Veech, Ketoacids? Good Medicine? 2003 http://okdentalwelln...3-Superfuel.pdf

So, if we take the data you give "70 mg of sodium and 100 mg of potassium for every 500 mg of butyric acid", the target 150g of butyric acid will result in 21g of sodium and 30g of potassium -ouch!

But how much of the stuff you take? The symptoms you describe are consistent with sodium overdose (like in a 'saline purge' == lotsa salt + water)

 

 

You are exposing the other end of the problem:  you don't get enough butyric acid in a supplement to make a physiological difference, if your objective is ketosis.

 

Obviously no one in his right mind is going to be taking 300 pills a day, and as you point out that then creates a massive sodium and potassium overload, potentially fatal in the case of potassium!

 

The more exciting nutrient is the ketone ester, which I spoke about in Dominic D'Agostino's ketogenic diet for cancer research.   That offers a way to very significantly increase ketone levels without requiring an excessive intake of minerals.   

 

I'm also intrigued by Tributyrin, which is a triglyceride form of butyrate.   Does anyone know if that is delivered in food additives as a pure triglyceride or does it require binding to a sodium salt?

 

P.S., I get the symptoms of gas and loose bowel ingesting a SINGLE butyrate tablet twice a day.   That's 140 mg of sodium and not worth serious consideration for a side effect.   I am able to ingest 3 grams of sodium through sea salt and sodium bicarbonate daily without any gastrointestinal side effects, so I have to believe it is not the sodium that is creating the bad gastro effects for me.   I don't get any kind of blood pressure effect from that much salt at all.

Edited by pone11, 04 February 2015 - 02:57 AM.

[xEva]

You're right, one-two caps of sodium βHB don't have enough Na or K to qualify for overdose of anything. But you recon how much butyric acid is required "to make make a physiological difference, if your objective is" increase in GDF11?

[pone11]

You're right, one-two caps of sodium βHB don't have enough Na or K to qualify for overdose of anything. But you recon how much butyric acid is required "to make make a physiological difference, if your objective is" increase in GDF11?

 

I was not the person who put forward this idea.   I doubt that butyrate would create the amounts of GDF11 that are needed to reverse aging.

[Bryan_S]

We may not be able to agree on Niacin, Nicotinamide and Nicotinamide Riboside Bryan but here we do. 

 
The are ten gut bacteria for every cell that makes up our body and they are all excreting the substances we live on.
Put another way:  We all live on bacteria shit... (sung to the tune of Yellow Submarine) 
That being the case;  its a damn good idea to make sure we approve of what the bacteria are excreting and hence said bacteria!
 
While GM  bacteria are a thing of the future and I worry about who will own the synthetic amino's used to control them and hence us,  there are countless natural bacteria science is unaware of.

 

We agree more than disagree and I believe our goals are the same. Our conversations may even entertain others.

 

We already contain a natural protein expression system as I was eluding. I've thought about what happens in these recombinant protein expression systems and with the exception of the drawn out purification steps the same thing is taking place within our gut anyway. Why not go directly to the source. I mention the GM bacterias synthetic amino acid dependence because it would be easy to rid your self of them if needed. You wouldn't want to be stuck with a GM if it wasn't providing you with what you need or doing you harm.

 

We contain 30 to 40 different types of bacteria. The selection of the proper spices would be important. 

 

They've tested mice in sterile conditions with no gut bacteria and the odd thing is they need to consume about 30% more calories just to survive. We are totally intertwined with the little buggers and they provide us many services. They also train our immune systems and battle foreign invaders.

 

Food for thought but going forward we need more information on how much GDF11 a person needs. We are bit early to try and size up this equation. 

[pone11]

 

Food for thought but going forward we need more information on how much GDF11 a person needs. We are bit early to try and size up this equation. 

 

 

I think we have a pretty decent idea how much GDF11 a person needs.   The mice studies dosed at injections of 0.1 mg/kg every day.   This dose documented in the original study here:

http://www.sciencema...4/6184/630.full

 

So humans might require 50% more or 50% less, but I think human studies could use a mouse study as a starting point and pretty quickly zero in on the effective minimum and maximum doses.   It's not like we have no idea about the order of magnitude required.

 

The problems future biohackers need to solve are:

 

1) How do we get a blood test to measure GDF11, so we can understand whether we are hitting target levels or overdosing.

 

2) How can we get it cheaply enough to take the large required doses without it bankrupting you.

[pone11]

I have a pure hypothesis about GDF11 that might explain why:

 

1) It was required in mouse studies at large doses, daily

 

2) It's benefits wore off after about three weeks

 

The hypothesis is that plasma of young people contain correct levels of multiple peptides, proteins, and enzymes compatible with "youthfulness" of the entire cellular environment.   When an old person is injected with plasma, they are getting that cellular environment temporarily revitalized.   But, in effect, the older person is just "borrowing" these metabolites.  They use them up, and after a few weeks the old person must rely on their existing cellular machinery to produce new proteins, peptides, and enzymes, and that machinery is "old".   They cannot sustain the correct cellular environment for youth on their own.

 

Many of these metabolites are being produced by mitochondria.    And since it is the mitochondria that most easily get damaged as we age, my inference is that the old person's mitochondria is largely what is responsible for failure to produce the right levels of all of the necessary metabolites.    GDF11 is just one of these metabolites, and it is a very important one that apparently accounts for a large part of the benefit when a young person's plasma is transfused to an older person.

 

In the shortest term, they will use plasma and/or GDF11 to study these effects in humans.    As a next step, they will identify other proteins, peptides, and enzymes, that allow them to get 90%+ of the benefit of transfusing plasma, without needing to use plasma.   But, ultimately, the only way to "permanently" correct the defects in the older person's cellular environment would be to replace the mitochondria with newer ones.   That leads us to the thread I started about mitochondrial transplants:

http://www.longecity...al-transplants/

 

Again, this is just hypothesis, but it seems like a reasonable course that this research will follow.

[zorba990]

Some sources:
Tributyrate from sigma
http://www.sigmaaldr...ng=en&region=US
$110 / kg sounds cheap compared to these peptides!

25% off custom peptides from Genscript this month:
reference the promo code Calendar02P25 by February 28, 2015

I am not affiliated with either of these guys...

Edited by zorba990, 04 February 2015 - 08:33 PM.

[niner]

 

Food for thought but going forward we need more information on how much GDF11 a person needs. We are bit early to try and size up this equation. 

 

I think we have a pretty decent idea how much GDF11 a person needs.   The mice studies dosed at injections of 0.1 mg/kg every day.   This dose documented in the original study here:

http://www.sciencema...4/6184/630.full

 

So humans might require 50% more or 50% less, but I think human studies could use a mouse study as a starting point and pretty quickly zero in on the effective minimum and maximum doses.   It's not like we have no idea about the order of magnitude required.

 

The problems future biohackers need to solve are:

 

1) How do we get a blood test to measure GDF11, so we can understand whether we are hitting target levels or overdosing.

 

2) How can we get it cheaply enough to take the large required doses without it bankrupting you.

 

You need more than just knowing what your blood level is, you also need a marker that tells you that it's "enough", or that it's "working".  I suppose you could shoot for a youthful blood level, if we know what that is.   That should eliminate the need to extrapolate from the mouse dose.  The typical mouse/human HED is that the human needs 1/12 the amount the mouse needs.  If you're 65 kg, then you'd need

 

65kg * (0.1mg/kg) * (1/12) = 0.5 mg.  That's if you inject it.  I don't see this working without injecting, due to the size of GDF11

[niner]

2) It's benefits wore off after about three weeks

 

Many of these metabolites are being produced by mitochondria.

 

 

Wait, do you mean the benefits wore off after 3 weeks when they kept giving the mice GDF, or if they stopped giving it to them?  If that former, that's a really bad sign.  Hope it's the latter.

 

Do we know that GDF11 is produced in the mitochondria?  Or any of these paracrine factors?  Or is that just a hypothesis?

[Bryan_S]

 

2) It's benefits wore off after about three weeks

 

 

Wait, do you mean the benefits wore off after 3 weeks when they kept giving the mice GDF, or if they stopped giving it to them?  If that former, that's a really bad sign.  Hope it's the latter.

 

No No No . . . I posted the article answering many of these questions already before, this is a repost from awhile back from our esteemed Amy Wagers speaking to Bioscience Technology last December 2014: Link http://www.bioscienc...4-breakthrough#

 

Excerpt emphasis mine:

Wagers is headed for clinical trial as well, but wants to answer many questions first. Her group has finished the first of three studies gauging how long effects of GDF11 last. The above 2005 paper showed effects of parabiosis lasted three weeks, the time span studied. “A really important question is `Do you need to continuously supply the factor, or does it re-set the system?’ So far there is some evidence it re-sets.” The Stanford transfusion work is encouraging as “it says whatever activity is causing the changes persists in plasma for a period of time.” Aging may be about “imbalance of signals.”

 

She has 2 more studies with animals before people. She believes the evidence suggests the level re-sets. This would be phenomenal if proven true, this question however will be investigated with further clarity. Amy Wagers is not rushing the science and wants to define the nuances before moving into human tissue. She has chastised her colleagues for rushing into the plasma studies. She is afraid they might set the entire field of study back.

 

As far as testing levels here is a quote: She continued: “Then, through cardiologist Rich Lee of Harvard, we had a collaboration with Somalogics, a biotech that does aptamer-based screening of proteins in circulation. They analyzed for us the blood of young and old mice and found 13 analytes that reliably distinguished young versus old. Number two on that list was GDF11. So we got excited about GDF11. It was pulled out of the screen, and it was in the signaling pathway that we knew was deregulated and restored after heterochronic parabiosis.”

 

Follow the Somalogics link above, data may already be out there as many are asking these very same questions, if we knew what youthful levels were we'd have a better handle and know what to shoot for. 

Edited by Bryan_S, 04 February 2015 - 10:42 PM.

[Logic]

I asked TLR about GDF-11
Apparently recombinant peptides are more milligram affairs. One gram would likely cost over $20k

A minimum run to get the price to something remotely reasonable is expensive.
Their guess is something on the order of $200 per 500mg would be a ballpark estimate, requiring a minimum of ~20 people.

Those are guestimates and they really just do not know offhand.

I think another 'group buy' like the GHK/GHK-Cu one is a good possibility, if enough people show interest.
I think the price may be worth it?

[PWAIN]

Is that correct, TLR think they may be able to source GDF-11 for $200 for half a gram if they can get 20 people interested????

 

If they can do this as injectable, we could inject about 0.5mg to 1mg a day and get the required amount for effacy according to niners calculation. That is enough to inject daily for about 2 years!!!!

 

I'm IN!!!! Put me down for 500mg for $200.

 

 

I asked TLR about GDF-11
Apparently recombinant peptides are more milligram affairs. One gram would likely cost over $20k

A minimum run to get the price to something remotely reasonable is expensive.
Their guess is something on the order of $200 per 500mg would be a ballpark estimate, requiring a minimum of ~20 people.

Those are guestimates and they really just do not know offhand.

I think another 'group buy' like the GHK/GHK-Cu one is a good possibility, if enough people show interest.
I think the price may be worth it?

 

[Logic]

Is that correct, TLR think they may be able to source GDF-11 for $200 for half a gram if they can get 20 people interested????
 
If they can do this as injectable, we could inject about 0.5mg to 1mg a day and get the required amount for effacy according to niners calculation. That is enough to inject daily for about 2 years!!!!
 
I'm IN!!!! Put me down for 500mg for $200.
 

I asked TLR about GDF-11
Apparently recombinant peptides are more milligram affairs. One gram would likely cost over $20k

A minimum run to get the price to something remotely reasonable is expensive.
Their guess is something on the order of $200 per 500mg would be a ballpark estimate, requiring a minimum of ~20 people.
Those are guestimates and they really just do not know offhand.

I think another 'group buy' like the GHK/GHK-Cu one is a good possibility, if enough people show interest.
I think the price may be worth it?

I got the impression they would make or have it made.
The prices etc. are still very much up in the air but you never know.

Lets see who else is interested.

[PWAIN]

Ok, to gauge intrest, I would like to start a new thread to see if others would like to participate if this becomes available. I would title it:

 

GDF-11 Group Buy @$200 for 500mg (~2 year supply) would you be interested in joining?

 

We can then see how many people put their hands up. I will make clear in the body of the message that this is just a guestimate at present.

 

Does that sound ok?

 

[pone11]

 

2) It's benefits wore off after about three weeks

 

Many of these metabolites are being produced by mitochondria.

 

 

Wait, do you mean the benefits wore off after 3 weeks when they kept giving the mice GDF, or if they stopped giving it to them?  If that former, that's a really bad sign.  Hope it's the latter.

 

Do we know that GDF11 is produced in the mitochondria?  Or any of these paracrine factors?  Or is that just a hypothesis?

 

 

I have no idea where or how GDF11 is produced.  Just from intuition since the mitochondria accumulate the most damage as we age, that's a place to be looking for things that might dysregulate key metabolites.  

 

See next post for issues around when it wears off.

Edited by pone11, 05 February 2015 - 02:13 AM.