386 replies to this topic

[bmarcello]

Thanks Steve for sharing your experience.
I would like to post a thought I have on the "reset theory". Maybe someone tested it already or might trigger a mice study.

My thought is: Considering the human body is like a tank leaking ~1% per year of GDF11 (body production is lower than body consumption) and in about 3 months is reset/refilled, in case the refill is stopped, will the body require some years to empty again? This will demonstrate the theory.
I guess if anyone stopped GDF11 and experienced this slow leaking again.

Thanks all for sharing in case familiar with above.
Marcello

[echoman]

Here is the original website for the seller on Amazon http://www.biomatik....10ug-59999.html

 

Looks like one can save about 30 bucks on shipping. Also, they sell up to 100ug for $759.

[Nate-2004]

Thanks for the link Echoman. That helps. I am still unsure about going through with testing GDF-11. Has anyone else been trying it? Some have said don't bother it does nothing, but that came from a 30 year old. I'd like to see what happens with someone much older besides Steve.

 

BTW This guy isn't a biologist and today I'm a little more skeptical of his opinions but he makes an interesting point regarding parabiosis towards the end of this article. 

 

 

 

In my opinion, the existing evidence heavily favors the hypothesis that aging is caused by epigenetic changes, rather than the other way around.  When we look at the kinds of changes that occur, they seem to be pouring fuel on the fire, not putting it out.  Protective genes are turned off and inflammatory genes are turned up.  I also think that parabiosis experiments provide a strong clue.  Three researcher groups (at Stanford Harvard, Berkeley) have shown that injecting blood plasma from a young mouse into an old mouse makes the old mouse healthier, and relieves some problems associated with age.  The blood plasma contains no cells—only signal molecules that are the product of gene expression.  This is powerful evidence that youthful gene expression is supporting a strong and youthful body, and (conversely) that the kind of gene expression that characterizes old age is not doing the body any good.

But the ultimate experiment will be to re-program gene expression in an old mouse and see if there is a rejuvenating effect.

 

Read full article for context.

Edited by Nate-2004, 09 January 2017 - 04:07 PM.

[stevegperry]

Here's my reply to above questions:

 

My thought is: Considering the human body is like a tank leaking ~1% per year of GDF11 (body production is lower than body consumption) and in about 3 months is reset/refilled, in case the refill is stopped, will the body require some years to empty again? This will demonstrate the theory.
I guess if anyone stopped GDF11 and experienced this slow leaking again.

 

I don't know anyone who has taken a break from GDF11 and done biomarkers to see if there is any decline.  I did take a month long break from GDF11 and did take a skin elasticity test after this break.  My skin age went up from 40.5 to 44 which does suggest that stopping GDF11 supplementation will start you declining/aging a bit.  And anecdotally, I felt like my favorite thing about GDF11, stamina, was starting to flag a bit.  But we really need more hard biomarker data after GDF11 cessation to make this call.  

 

My gut says that you must keep on taking GDF11 to slow aging as much as possible.  Though once the "tank is filled"/you are down regulated, you don't need much.  My current dose is .5 ng/day.

 

As for the 30 year old, I have talked to him.  Yes, it would be hard for a 30 year old to notice much change on GDF11 without comprehensive biomarkers.  And note for someone that young, even 1 ng/day of GDF11 is a big dose.  My advice to young people taking GDF11 is to take a full set of biomarkers every year.  If they improve or even remain the same over time, this is a huge win....

 

As for people who have had positive experiences with GDF11, please review my download site, GDF11Rejuvenation.com.  There is also a link to my Raadfest talk on the site. I just had four people take a  full set of baseline biomarkers before starting their GDF11 regimen.  So assuming they all go for the same set of biomarkers after 3 months on GDF11, I should have more than double the amount of data on GDF11 efficacy by April.

 

[bulky]

Hi

I looked into GDF11 about a year ago but I ran into a brick wall when I tried to find a good source. I promised myself I'd take a another look when I had some time. Thanks for the posts Steve. Has anyone else been taking it regularly? Have any other research studies been released?  

Any updates appreciated.

Thanks!

[bmarcello]

https://www.ncbi.nlm...?i=3&from=gdf11

This is the answer that telomers length are the consequence of aging and not the cause of aging.
Average telomere length decrease with age, while stem cells proliferation and repair add new cells that are the "youngest" and therefore the average telomeres length in a tissue increase or become/remain young/er

Article is quite important on GDF11 results on myocard damage and the repair effects through stem cells proliferation via GDF11.
I suspect GDF11 act on LGR5 gene that stimulates the stem cells proliferation... studies will tell.

Edited by bmarcello, 05 March 2017 - 06:05 PM.

[Nuke]

Thanks you. I still have to work through the details of this study, but the case for GDF-11 looks better and better.

 

[bmarcello]

We need to thank Steve.

[albedo]

Article in the LEF Research Update of March 2017 on GDF-11, in case you missed it:

http://www.lifeexten...eversal/Page-01

[ta5]

What's the deal?

 

EMBO Mol Med. 2017 Mar 7. pii: e201607231.
Supraphysiological levels of GDF11 induce striated muscle atrophy. (free full study)

Department of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA lsweeney@ufl.edu.

Abstract

Growth and differentiation factor (GDF) 11 is a member of the transforming growth factor β superfamily recently identified as a potential therapeutic for age-related cardiac and skeletal muscle decrements, despite high homology to myostatin (Mstn), a potent negative regulator of muscle mass. Though several reports have refuted these data, the in vivo effects of GDF11 on skeletal muscle mass have not been addressed. Using in vitro myoblast culture assays, we first demonstrate that GDF11 and Mstn have similar activities/potencies on activating p-SMAD2/3 and induce comparable levels of differentiated myotube atrophy. We further demonstrate that adeno-associated virus-mediated systemic overexpression of GDF11 in C57BL/6 mice results in substantial atrophy of skeletal and cardiac muscle, inducing a cachexic phenotype not seen in mice expressing similar levels of Mstn. Greater cardiac expression of Tgfbr1 may explain this GDF11-specific cardiac phenotype. These data indicate that bioactive GDF11 at supraphysiological levels cause wasting of both skeletal and cardiac muscle. Rather than a therapeutic agent, GDF11 should be viewed as a potential deleterious biomarker in muscle wasting diseases.

PMID: 28270449

[Nate-2004]

There are so many contradictory studies on this that I think most researchers aren't even working with the same substance. It's like infrared light studies on skin and tissue. Many of them directly contradict each other.

Edited by Nate-2004, 10 March 2017 - 02:23 AM.

[bmarcello]

Did you read the article name? Particularly first word: Supraphysiological?
GDF11 dosage is important, anyway it is for all. Extra amount create issues as per Steve's feedback on his testing (GERD, insomnia, etc...)
It is not surprising the results if they overdosed GDF11, Steve mention nanograms per day for a person, while in the posted research they gave to the mouse 1 mg/kg... 1million times more...
You judge...

Edited by bmarcello, 10 March 2017 - 08:51 PM.

[stevegperry]

Thanks Marcello and yes, the keyword in this paper is "surpaphysiological".  As I have mentioned in my paper, my Raadrest talk and constantly to my cohort, the dosing window of GDF11 is very narrow and only tiny, ng level amounts are necessary to be effective.  Excess GDF11 can cause inflammation, dyspnea, anemia and other side effects.  As the paper mentions, GDF11 is 90% homologous to GDF8 (myostatin), so excess GDF11 almost certainly cross binds to myostatin sites, resulting in muscular atrophy.  Also, there is 500 times more myostatin in the body than GDF11, so you'd really need to overdose before you saw any muscular/cardiac atrophy.  The other side effects I just mentioned would certainly get you long before muscular atrophy was apparent.

 

At the end of the day, this paper is like saying we engineered mice to produce supraphysiological levels of GH and they all became acromegliacs and died.  Is this usual information?  I suppose.  But it certainly wouldn't dissuade you from using GH as an anti-aging therapy. 

 

The right dose is everything...

 

[bmarcello]

Maybe a doctor can help to better understand:
    On the article Supraphysiological levels of GDF11 induce striated muscle atrophy is written that “Recombinant GDF11 induces SMAD2/3 activation and atrophy in C2C12 myotubes”.
    Well
    On Wikipedia SMAD3 “SMAD3-knockout mice have diminished adiposity,[14] with improved glucose tolerance and insulin sensitivity. Despite their reduced physical activity arising from muscle atrophy” and also, “SMAD3 deficiency promotes inflammatory aortic aneurysms in angiotensin II-infused mice via the activation of iNOS. Macrophage depletion and inhibition of iNOS activity prevent aortic aneurysms related to SMAD3 gene mutation[16]”
https://en.wikipedia...legic_homolog_3

    So… the article is saying the opposite of Wikipedia studies.

    In my opinion….
GDF11 is activating SMAD or anyway is signaling there is stem-cells production -> downstream you are enabled to proliferate + macrophages duplicate and be activated. Downstream cells then received the input and senescent cells (if possible) are self-destroying themselves (apoptosis).
 

[bmarcello]

Maybe a doctor can help to better understand:
    On the article Supraphysiological levels of GDF11 induce striated muscle atrophy is written that “Recombinant GDF11 induces SMAD2/3 activation and atrophy in C2C12 myotubes”.
    Well
    On Wikipedia SMAD3 “SMAD3-knockout mice have diminished adiposity,[14] with improved glucose tolerance and insulin sensitivity. Despite their reduced physical activity arising from muscle atrophy” and also, “SMAD3 deficiency promotes inflammatory aortic aneurysms in angiotensin II-infused mice via the activation of iNOS. Macrophage depletion and inhibition of iNOS activity prevent aortic aneurysms related to SMAD3 gene mutation[16]”
https://en.wikipedia...legic_homolog_3

    So, the article is saying the opposite of Wikipedia studies. what am i missing or not properly reading?

    In my opinion….
GDF11 is activating SMAD or anyway is signaling there is stem-cells production -> downstream cells are enabled to proliferate + macrophages duplicate and be activated. Downstream cells then received the input and senescent cells (if possible) are self-destroying themselves (apoptosis).

 

Happy to read your analysis.

Thanks
 

[pone11]

As a counterpoint to this thread, Irina Conboy's team at Berkeley has recently suggested that the reason for the parabiosis experiment results may not be that young blood has proteins that cause youth.   Rather, it may be inverted, and old blood may have proteins that cause aging and need to be removed.  The young rats may effectively be acting as a filtration system for the older rats.   This thread on Longecity points to a recent Conboy interview that discusses their recent research that led them in this direction.   

 

I am actually more excited by that development because in theory it should be much easier to apply that to humans than any approach that is based on production of rare proteins.   Plasma filtering technology has been FDA approved for many diseases and adapting that to this application would probably be doable without a lot of new regulatory approvals.   Injecting rare proteins will require decades of human trials and what is the FDA regulatory process for a treatment that makes humans grow young?   

 

[Nate-2004]

Who here is going to give a **** about the FDA when that's discovered to be effective? If it is some kind of filtration system, hopefully it won't be difficult to copy, patented or not.

Edited by Nate-2004, 15 April 2017 - 01:07 PM.

[bmarcello]

Thanks for sharing.
This might work but acting downstream the aging process.
Senescent cells secrete cytokines (P16) to inform the body of their toxicity. Shared Article work might at this downstream level filtering those cytokines.
By acting upstream will provide better benefits as avoiding the cascade of the aging effects.
To act on senescent cells a new peptides has been tested (FOXO4-DRI) with much better rejuvenation effect.
Another way is to use telomere lengthening, hoping senescent cells will return back fully functioning,
Or even better, further upstream by acting on steam-cells and signaling them to proliferate and replace damaged/senescent cells. GDF11 could be a signal cytokines as is restoring neural/epithelial cells (I suspect it acts on LGR5+ gene that starts the proliferation).

Body is a well balanced system, well programmed, to replace senescent cells it is needed to have new cells available (or duplication but this lower the average telomeres length, or via stem-cells that increase the average of telomeres length).
I think a signal cytokines share the signal to proliferate to stem-cells and to go in apoptosis to senescent cells.
Study will tell us.
I bet with stem-cells proliferation signal and to accelerate anti aging via senescent cells apoptosis (to empty the road downstream and allow steam-cells to replinish killed cells).

Edited by bmarcello, 15 April 2017 - 03:41 PM.

[p3x888]

Would this site be a legit source?

https://www.mybiosou...ucts_id=1138720

[lost69]

i m getting all the stuff to start using 2 vials of gdf11, 5mcg each that i got

 

but i have a big problem, i can t find BD brand in europe and also scales are confusing since dosing is very very important in this case i can t make mistakes

 

does anyone know where to get these syringes in europe?

https://www.healthwa...ount-17335.html

 

what are the units of insulin?do they equal to 1ml?

 

i think using simple ml instead of insulin units would have been less confusing

 

thanks

 

 

[Felix375]

1 ml =100 insulin units.

 

You should be looking for 0.3cc syringes. They don't have to be BD. BDs are way more expensive.

 

 

[lost69]

1 ml =100 insulin units.

 

You should be looking for 0.3cc syringes. They don't have to be BD. BDs are way more expensive.

 

is this a 3cc syringe?

 

https://images-na.ss...31rQlRhMjDL.jpg

 

 

in europe they are all in ml scale, it says nothing about cc, i ve found plently of Us websites but they dont ship out of US

[Felix375]

Yes. that is what you want. It is NOT a 3cc but a 0.3cc. There's a big difference. 0.3cc = 0.3ml.

 

Make sure you don't get the 3cc or ml. They are way too big and you won't be able to tell how much to inject.

[Kaine]

i m getting all the stuff to start using 2 vials of gdf11, 5mcg each that i got

 

but i have a big problem, i can t find BD brand in europe and also scales are confusing since dosing is very very important in this case i can t make mistakes

 

does anyone know where to get these syringes in europe?

https://www.healthwa...ount-17335.html

 

what are the units of insulin?do they equal to 1ml?

 

i think using simple ml instead of insulin units would have been less confusing

 

thanks

 

I buy my medical gear from premierhh.co.uk - great service and good prices.

[lost69]

 

i m getting all the stuff to start using 2 vials of gdf11, 5mcg each that i got

 

but i have a big problem, i can t find BD brand in europe and also scales are confusing since dosing is very very important in this case i can t make mistakes

 

does anyone know where to get these syringes in europe?

https://www.healthwa...ount-17335.html

 

what are the units of insulin?do they equal to 1ml?

 

i think using simple ml instead of insulin units would have been less confusing

 

thanks

 

I buy my medical gear from premierhh.co.uk - great service and good prices.

 

 

thank you very much

[lost69]

Yes. that is what you want. It is NOT a 3cc but a 0.3cc. There's a big difference. 0.3cc = 0.3ml.

 

Make sure you don't get the 3cc or ml. They are way too big and you won't be able to tell how much to inject.

 

thank you very much, these are available all over the place...i have them at home too, never noticed the very small writing at the end of the scale 0.3ml/cc.

 

so i ll just need to fill it up completely to make 0.3cc and that s it

[bmarcello]

Hi,
Please read Steve's directions, it is needed tiny amount of molecule, below 1ng.
It is extremely important how is diluted the 5micrograms into bacteriostatic water. You need to calculate precisely.
Don't mess up otherwise it would be dangerous.
Ie. Diluting 5micrograms GDF11 into 30ml will provide 1.667ng/unit insulin syringe.
Again, follow correctly the instructions and all biomarkers to reduce the initial dose and titrate correctly. Use the log file created by Steve to monitor everything. Don't start without having the biomarkers done.
Ps. If you buy insulin syringe, those are standard everywhere in the world. If you find the 0.25ml is even better as again you need less than 1nanogram every other day after ~2 months (also with 0.25ml one unit will be 1.667 or depends on how you dilute).
Hope will help.

Edited by bmarcello, 28 May 2017 - 12:11 PM.

[lost69]

Hi,
Please read Steve's directions, it is needed tiny amount of molecule, below 1ng.
It is extremely important how is diluted the 5micrograms into bacteriostatic water. You need to calculate precisely.
Don't mess up otherwise it would be dangerous.
Ie. Diluting 5micrograms GDF11 into 30ml will provide 1.667ng/unit insulin syringe.
Again, follow correctly the instructions and all biomarkers to reduce the initial dose and titrate correctly. Use the log file created by Steve to monitor everything. Don't start without having the biomarkers done.
Ps. If you buy insulin syringe, those are standard everywhere in the world. If you find the 0.25ml is even better as again you need less than 1nanogram every other day after ~2 months (also with 0.25ml one unit will be 1.667 or depends on how you dilute).
Hope will help.

 

thank you marcello, i m studying every step very carefully, i am totally unfamiliar with insulin world and this is not good......so i am acting like a pure dummy even if i think i got what the correct scales are.

 

Steve says "each unit on the insulin needle equates to 1.66 ng of GDF11", what does he mean as "each unit"?one unit of insulin? 

 

i indicated what i mean as one unit on the picture attached, but you can t dose 0.5ng properly because every unit is 1.66ng........

Attached Files

•  sringhe insulina 0.3ml 0.3cc.jpg   39.01KB   4 downloads

[Felix375]

Hey Lost69,

 

You need to read Steve's guide very carefully. Make sure you pay attention to the units. You will be taking at max about 6 units to start with. NOT the entire syringe. That is a giant OVERDOSE.

 

0.3 cc = 30 UNITS. You will only be taking around 6 units to start and going DOWN to 0.6 units. Notice the ZERO and the decimal.

[lost69]

Hey Lost69,

 

You need to read Steve's guide very carefully. Make sure you pay attention to the units. You will be taking at max about 6 units to start with. NOT the entire syringe. That is a giant OVERDOSE.

 

0.3 cc = 30 UNITS. You will only be taking around 6 units to start and going DOWN to 0.6 units. Notice the ZERO and the decimal.

 

on 30ml/0.3cc syringe:

 

1 unit (0.01cc) = 1.66ng gdf11?

or

10 units (0.1cc) = 1.66ng gdf11?