374 replies to this topic

[rodentman]

Did he say this in a recent interview? I have not heard it from him, nor does he say so in his book.

 

E5 surely must be some combination of endogenous plasma signalling molecules like GDF11, Oxytocin, TIMP2, GnRH, Klotho, Humanin...

 

How else could Harold have come up with E5 in a short space of time before his Indian Visa expired, once he discovered they weren't able to perform a rat plasma exchange? Harold has proposed that a cell's age is guided by systemic factors, but he didn't do any of the actual work to discover what these factors might be himself - he got them from the literature, which we can all read.

 

For example in his 2015 paper he mentions the following:

 

 

 

 

In his book Harold states he carries out no dilution or removal of bad actors (like CCL-11, which he also mentions in his above paper), he just adds in good/'youthening' factors at a higher concentration than would normally be present in youthful plasma.

 

I like Harold and Akshay, who I've corresponded with before. But really, how are natural, endogenous substances patentable? I'm no expert on patent law, but I'd guess they'd have to patent the dose/timing/proprietary formulation. I doubt they'd be able to patent the 'use', i.e. aging, given they are going through the FDA, but I could be wrong. I also suspect that the exact combination of molecules in E5 will not be the only one that works, so others could find ways around any patent. 

 

Sorry if this is a little off topic, but it is relevant to GDF11, and I'd thought I'd give my 2 pence!  

 

I'd have to search for where he said it.  I only remember he was responding to a question about GDF11 from someone.

 

He's been very 'hush hush' about what E5 actually contains.  But he did let it 'slip' in his last interview that it will require the patient's blood to be removed, and then 'processed/mixed' and returned to patient.  He also said it involves a lot of actual 'volume'

 

@ 4:10

 

Here's the transcript:

 

Katcher:

  'It would actually be more of an infusion than an injection, because of the 'volume''  

 

Modern Healthspan:

'So you take some blood out, mix it up, and put it back'

 

Katcher:

'Yes'

[QuestforLife]

 

Here's the transcript:

 

Katcher:

  'It would actually be more of an infusion than an injection, because of the 'volume''  

 

Modern Healthspan:

'So you take some blood out, mix it up, and put it back'

 

Katcher:

'Yes'

 

 

That's very interesting. It certainly states in his book there is no dilution. I suppose rats only have about 15ml of plasma and we have say, 3L. So we'd need 200x the amount. I don't see why they can't just increase the concentration of the endogenous substances. Maybe there is some limit to how concentrated they can be (for safety?) so they've had to go for an IV bag and add them more slowly. Of course this then means they will be adding saline and albumin and by definition will be doing dilution. 

[rodentman]

That's very interesting. It certainly states in his book there is no dilution. I suppose rats only have about 15ml of plasma and we have say, 3L. So we'd need 200x the amount. I don't see why they can't just increase the concentration of the endogenous substances. Maybe there is some limit to how concentrated they can be (for safety?) so they've had to go for an IV bag and add them more slowly. Of course this then means they will be adding saline and albumin and by definition will be doing dilution. 

 

I really don't know.  Something in E5 isn't easily scalable... at least not at the current time.   Katcher says he had to develop devices/skills that never existed before in order to do this scaling.  He also says its a 'substance' and not a drug... which may just be how he likes to refer to it.

 

One thing to keep an eye out for is the current longevity rat study.  The 8 rats are ~ 3 years old, and on their 3rd dose, and a couple of the control rats have already died.  So if they are all still alive in early 2022... that's a very good sign, and if they are all still alive in 12 months, in all likelihood, this points to E5 'curing' aging.  So 2022 will potentially be an exciting year.

 

This convo should probably be moved to the E5 thread.

[ortcloud]

I really don't know.  Something in E5 isn't easily scalable... at least not at the current time.   Katcher says he had to develop devices/skills that never existed before in order to do this scaling.  He also says its a 'substance' and not a drug... which may just be how he likes to refer to it.

 

 

He says the answer is in the literature, so it is a secret hiding in plain sight.

My guess is that E5 is the TET demethylase enzyme.

[lost69]

i am really having a hard time getting bacteriostatic water from uk, and all shipments in general

 

do you have reliable suppliers for bac water and peptides in europe?

 

thank you

[thomasanderson2]

Thread Bump!

 

News or Reports?
News on the GDF-11 front anyone? 

Report from or about test subjects? 

I'm considering resuming my GDF 11 trials. During my GDF-11 trial 4 years ago, I observed major subjective and measured results to my test subject.

Biomarkers including cardiac, pulmonary, neurological, etc. The most dramatic improvement was a more than two decades (> 20 years!) improvement in certain cardiac measures (If I recall correctly, baseline for other markers started out excellent and did not exhibit those improvements).
 

*Sources for GDF-11?

I’ve ordered from Miltenyi Biotec before and I recall them being regarded as a quality lab.

$85 for 5ug

 

But earlier in this thread, R&D systems was referred to as a very high quality source - although notably more expensive. 

$377 for 10 ug

 

Mixing?

For reference, still posted in the earlier Mixing GDF11 and Dilutions Calculator

I've also done some of my own calculations - slightly different approach as follows:

* Vial 0 (The reconstitution vial when starting with 5ug or 5 Microgram) - add 1 ML Bacteriostatic Water (BAC). Result = 5ug/ML concentration.

* Vial 1 (30 ML BAC start) First extract 6 ML (BAC) then add the entire 1 ML reconstituted Vial 0.
Result = 5 ug/25ML = 0.2 Microgram/ML = 200 nanogram/ML = 200,000 picogram/ML

* Vial 2 (30 ML BAC start) First extract 10.5 ML (BAC) then add 0.5ML vial 1.
Result = 0.1 ug/20ML = 0.005 Microgram/ML = 5 nanogram/ML = 5000 picogram/ML

 

* Vial 3 (30 ML BAC start) First extract 10.5 ML (BAC) then add 0.5ML vial 2.
Result = 0.0025 ug/20ML = 0.000125 Microgram/ML = 0.1250 nanogram/ML = 125 picogram/ML =

1.25 pg per injectable unit


 

 

 

 

[Mind]

I am lining up a new interview with Steve Perry - hopefully within a matter of weeks.

[thomasanderson2]

I am lining up a new interview with Steve Perry - hopefully within a matter of weeks.

 

Great to hear that, Mind - very encouraged that Steve Perry still connected with this forum!

Thanks for the update.

[thomasanderson2]

OK, folllow up question on my own post:
 

Mixing?

For reference, still posted in the earlier Mixing GDF11 and Dilutions Calculator

I've also done some of my own calculations - slightly different approach as follows:

* Vial 0 (The reconstitution vial when starting with 5ug or 5 Microgram) - add 1 ML Bacteriostatic Water (BAC). Result = 5ug/ML concentration.

[Omitted]

 

* Vial 3 (30 ML BAC start) First extract 10.5 ML (BAC) then add 0.5ML vial 2.
Result = 0.0025 ug/20ML = 0.000125 Microgram/ML = 0.1250 nanogram/ML = 125 picogram/ML =

1.25 pg per injectable unit

 

Question:
* When you receive 5ug from a (reputable) lab - how confident are we that it's actually 5 micrgrams and not 10 micrograms? or even 10 milligrams?!?
* Is there some kind of generally acceptable +/- percentage amount?
* Would it makes sense to ask a lab this question?

NOT unique to GDF-11 of course, but the accuracy of the protocol and mixing process entirely depends on assumption that we have the correct starting weight.

Thanks for any insights!

Edited by thomasanderson2, 31 January 2023 - 07:15 PM.

[Mind]

The newest podcast with Steve is now live. A little review and a lot of new data about GDF11, biomarker results, recent research, etc...

[QuestforLife]

Agree with Steve that methylation tests are BS.

 

HRV improvement of 25% seems implausible; RMSSD maybe. 

[thomasanderson2]

OK, folllow up question on my own post:
 

 

Question:
* When you receive 5ug from a (reputable) lab - how confident are we that it's actually 5 micrgrams and not 10 micrograms? or even 10 milligrams?!?
* Is there some kind of generally acceptable +/- percentage amount?
* Would it makes sense to ask a lab this question?

NOT unique to GDF-11 of course, but the accuracy of the protocol and mixing process entirely depends on assumption that we have the correct starting weight.

Thanks for any insights!

I received an answer from a reputable lab on this subject of product weight
Turns out, the "weight" is actually determined by biological activity.
I'm slightly paraphrasing the reaponse:

****************

if reproducibility is the main issue of the question, the concentration of a cytokine is not the best parameter upon which to base the experiments but rather the biological activity.

For all of our cytokines we guarantee the biological activity as specified in the release criteria and stated on the respective product page in the details section.

However, since the activity of cytokines might be subject to minor changes from lot to lot, the specific biological activity shall be estimated with every different lot.

The latter shall be estimated empirically by performing a titration of the cytokine and observing which concentration induces the 50% of the total response (ED50).
The biological activity can then be calculated in U/mg with the following formula:

Biologial Activity (in U/mg): 1/ED50(in ng/ml) x 10E6

Knowing the biological activity of a given lot of cytokine will ensure reproduceable results when stimulating the cells for experiments

****************

 

[Mind]

A large observational study finds GDF11 (higher?) levels are associated with asthma, immune function, thyroid issues, and lung function.

[stevegperry]

Mind,

 

Thanks for posting the Novel insights paper on high GDF11 levels being correlated with asthma, reduced immune function and hypothyroidism.  You actually don't even have to know what GDF11 is to refute this paper since it is logically flawed and falls into the "true, true, no causal relationship" category.  

 

Let's start with the classic example of this flawed thinking:

 

What is wrong with this statement: Ice cream sales go up in the summer, the murder rate goes up in the summer, therefore ice cream causes murder

 

ChatGPT

The statement you provided is an example of a logical fallacy, specifically a spurious correlation or false cause fallacy. This fallacy occurs when two events or statistics correlate with each other but there is no causal relationship between them. The error lies in the assumption that correlation implies causation. In this case, the increase in ice cream sales during the summer and the increase in the murder rate during the same period are both true, but they are correlated with a common third factor — warmer weather or seasonal variations — rather than ice cream sales causing an increase in murder rates.

Warm weather or summer months might lead to more people being outdoors, including both increased social activities where ice cream is consumed and, unfortunately, potentially higher rates of certain crimes. However, implying that ice cream sales directly cause an increase in murder rates overlooks the complex socio-economic and environmental factors that influence crime rates. It's crucial to distinguish between correlation (a mutual relationship or connection between two or more things) and causation (one event is the result of the occurrence of the other event) when interpreting data and making arguments.

 

Well even Chat GPT sees the flaw in the above, which shows some pretty incredible reasoning for a piece of software!  So let's look at asthma - just because most people who have asthma have elevated GDF11 levels doesn't say much.  The fact of the matter is that most asthma diagnosis are made in childhood, when GDF11 levels are high.  But so are GH and IGF-1 levels.  So why not blame GH and IGF-1 for asthma too? 

 

Of course, you all know that I am completely biomarker driven, so the best way to refute this paper is to look at spirometry biomarkers like FEV1 and PEF as well as immune biomarkers like naive T's and CD4/CD8. I spent hundreds of thousands on biomarkers for early GDF11ers back in 2014.  And all GDF11ers now are required to take extensive baseline and post GDF11 biomarkers such as the UCLA immune panel, spirometry and CNS Vital Signs.  And I can assure you that no one has ever seen FEV1 or PEF go down on GDF11 and most people improve their spirometry biomarkers.  Needless to say, if GDF11 caused asthma, the FEV1 and PEF would tank for many people.

 

As for immune function being reduced by GDF11, this is definitely not the case.  We often double naive T's and significantly raise CD4/CD8 ratios.  MOA is GDF11 repairing and reactivating senescent hematopoietic stem cells. Improving immune competency is unquestionably one of GDF11's strongest suits.

 

One last thought - check out Xprize.org/health and note that I have entered GDF11 in the competition.  Yes, the upside of 101 million dollar prize is nice, but as usual, it takes money to make money.  I estimate to fulfill their requirements of double blind offshore clinical trial will easily cost over $1,000,000 which I will have to personally pay for.  But since the prize is heavily weighted towards immune and cognitive biomarkers, which are GDF11's strongest suits, I think GDF11 has a decent shot at winning the prize.  So I will happily fund the clinical trials.  If any aspect of the above paper is true, do you really think that'd I'd put this kind of money at risk as well as put trial participants at risk?

 

 

 

 

[Mind]

Thanks for your input on this recent study Steve. I am aware of the flaws in the study and of course "correlation does not mean causation". It only becomes a concern when multiple studies confirm the original premise/result.