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Nugenics "Elixir"

aging reversal epigenetics dna methylation clock heterochronic parabiosis programmed aging

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#151 smithx

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Posted 02 September 2021 - 03:00 AM

Haven't watched these two yet, but I wish he looked more rejuvenated himself.

 

Does he say he hasn't tried it on himself yet?


Edited by smithx, 02 September 2021 - 03:00 AM.

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#152 albedo

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Posted 19 September 2021 - 08:47 AM

A presentation by Harold Katcher yesterday, interviewed by David Wood (HK presentation starts at 17:55)


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#153 JamesPaul

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Posted 19 September 2021 - 03:08 PM

Haven't watched these two yet, but I wish he looked more rejuvenated himself.

 

Does he say he hasn't tried it on himself yet?

Correct,  he has not used E5 (the current name for what was formerly called "the elixir") on himself.



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#154 smithx

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Posted 22 September 2021 - 03:41 AM

Correct,  he has not used E5 (the current name for what was formerly called "the elixir") on himself.

 

And... why not?



#155 rodentman

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Posted 22 September 2021 - 05:45 PM

And... why not?

 

 

He hasn't made enough for a human dose.   His team has been focused on scaling up E5 to quantities for the last year.   He said the process involves taking out blood, and 'processing it' with E5, then re-injecting it.   He has said he will be likely the first to take it, as he doesn't have that long of a shelf-life.  He estimates human trials will start in 2 years, but he has implied that he may not wait that long.

 

Still only being done in rats in a longevity study, since they require so little, but the data so far, after 6 months looks very promising.


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#156 Nicolas Chernavsky

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Posted 25 September 2021 - 07:41 PM

Hi everybody, I'm Nicolas Chernavsky, from NTZ, a publisher specialized on the rejuvenation field. Some weeks ago, on September 4th, we published the book The Illusion of Knowledge, by Harold Katcher, in an event in San Francisco (CA-USA) in a bookstore called Book Passage (Ferry Building). Now, my wife Nina (who is one of the publishers of the book as well) and I are starting a newsletter to inform everyone about the activities of the company in which Harold Katcher is CSO, Yuvan Research, regarding the development of E5 and the rejuvenation therapies. The link of the newsletter is https://www.ntzplural.com/newsletter .


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#157 ortcloud

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Posted 03 November 2021 - 08:28 PM

Who wants to guess what the E5 is?

 

Harold says it is in the literature, so if you search on pubmed enough and connect the dots as Harold has said, you can find it.

 

 



#158 albedo

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Posted 06 November 2021 - 09:14 PM

Hi everybody, I'm Nicolas Chernavsky, from NTZ, a publisher specialized on the rejuvenation field. Some weeks ago, on September 4th, we published the book The Illusion of Knowledge, by Harold Katcher, in an event in San Francisco (CA-USA) in a bookstore called Book Passage (Ferry Building). Now, my wife Nina (who is one of the publishers of the book as well) and I are starting a newsletter to inform everyone about the activities of the company in which Harold Katcher is CSO, Yuvan Research, regarding the development of E5 and the rejuvenation therapies. The link of the newsletter is https://www.ntzplural.com/newsletter .

I look forward to read the book which I just purchased. I am intrigued by Harold's approach to aging research and in general by what he said in several occasions on his motivations and philosophy. Will see and I will also see after about E5. Thank you for the information.



#159 rodentman

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Posted 15 November 2021 - 09:55 PM

Attached File  e5-graph-11-15-21.jpg   52.96KB   1 downloadsAn update.  I just heard the 2nd control rat on the E5 longevity study died, all E5 rats are still alive.
 
I figured I'd chart this out.   I included the recently completed Dr. Goya young blood study to it for reference.  They both use 8-9 female Sprague Dawley rats, but you'll notice the control's of the two study don't match, and that is not unexpected, since they don't share the same supplier, diet, etc.  I just included it for reference, but of course use the E5 control rats for efficacy here.
 

e5-graph-11-15-21.jpg


Edited by rodentman, 15 November 2021 - 10:00 PM.

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#160 QuestforLife

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Posted 19 November 2021 - 02:53 PM

Who wants to guess what the E5 is?

 

Harold says it is in the literature, so if you search on pubmed enough and connect the dots as Harold has said, you can find it.

 

Elixir/E5 is GHK-CU or just plain GHK.

 

Discuss...


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#161 rodentman

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Posted 19 November 2021 - 07:56 PM

Elixir/E5 is GHK-CU or just plain GHK.

 

Discuss...

 

No its not.  You are thinking of the 'blue gel', which has nothing to do with E5, and has no shared ingredients, or shared methods of production.  The 'blue gel' is just a topical treatment, that helps improve the skin.  From what I've heard, its easy to produce in larger amounts, and may very will include GHK-CU.  It's basically an attempt to raise more money for the E5 production process.


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#162 QuestforLife

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Posted 19 November 2021 - 08:57 PM

No its not. You are thinking of the 'blue gel', which has nothing to do with E5, and has no shared ingredients, or shared methods of production. The 'blue gel' is just a topical treatment, that helps improve the skin. From what I've heard, its easy to produce in larger amounts, and may very will include GHK-CU. It's basically an attempt to raise more money for the E5 production process.


Yeah that's what's been claimed.

I am just putting forward the hypothesis that E5 itself is also GHK-Cu or even just plain GHK.

GHK is a peptide that exists in the plasma and declines with age.

It is released on damage to the ECM, it takes copper from albumin, and triggers rejuvenation in a range of cells and tissues. This rejuvenation has been previously attributed to the antioxidant actions of copper (boosting copper/zinc-superoxide dismutase). But more recently it has been attributed to a resetting of gene expression to a more youthful profile.

The following review paper is pertinent:

GHK and DNA: Resetting the Human Genome to Health

During human aging there is an increase in the activity of inflammatory, cancer promoting, and tissue destructive genes plus a decrease in the activity of regenerative and reparative genes. The human blood tripeptide GHK possesses many positive effects but declines with age. It improves wound healing and tissue regeneration (skin, hair follicles, stomach and intestinal linings, and boney tissue), increases collagen and glycosaminoglycans, stimulates synthesis of decorin, increases angiogenesis, and nerve outgrowth, possesses antioxidant and anti-inflammatory effects, and increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells. Recently, GHK has been found to reset genes of diseased cells from patients with cancer or COPD to a more healthy state. Cancer cells reset their programmed cell death system while COPD patients’ cells shut down tissue destructive genes and stimulate repair and remodeling activities. In this paper, we discuss GHK’s effect on genes that suppress fibrinogen synthesis, the insulin/insulin-like system, and cancer growth plus activation of genes that increase the ubiquitin-proteasome system, DNA repair, antioxidant systems, and healing by the TGF beta superfamily. A variety of methods and dosages to effectively use GHK to reset genes to a healthier state are also discussed.

Source:https://www.hindawi....ri/2014/151479/


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#163 rodentman

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Posted 19 November 2021 - 11:34 PM

Yeah that's what's been claimed.

I am just putting forward the hypothesis that E5 itself is also GHK-Cu or even just plain GHK.

GHK is a peptide that exists in the plasma and declines with age.

It is released on damage to the ECM, it takes copper from albumin, and triggers rejuvenation in a range of cells and tissues. This rejuvenation has been previously attributed to the antioxidant actions of copper (boosting copper/zinc-superoxide dismutase). But more recently it has been attributed to a resetting of gene expression to a more youthful profile.

The following review paper is pertinent:
 

 

I am a big believer in GHK-Cu, and I use it myself.    But the results that came out from the first study, (and appear to be being repeated in this study) are so beyond the pale of anything else I've seen.   Also, unlike the other the other epigenetic clocks, the GrimAge clock is difficult to 'fool'.

 

I think there are a few possibilities here:

1. E5 is a big hoax perpetrated by Katcher and S. Horvath.

2. E5 is a big hoax perpetrated by Katcher, as he was able to engineer rats with wildly different epigenetic tissue ages, and fooled S. Horvath into believing they were chronologically 25 months old.

3. E5 does reduce the epigenetic age of tissues by an average of 54%, and greatly improves the rats healthspan, but like nearly every other therapy, it 'peters out' as the rat reaches its programed max age, and doesn't significantly increase the rat's lifespan.

4. E5 can reprogram a rat's age, and extend its maximum lifespan indefinitely, but it won't work in humans.

5. E5 can reprogram a rat's age, and extend its maximum lifespan indefinitely.

 

1 & 2 seem very unlikely, based on the track record of both Katcher and Horvath.

My gut instinct is telling me 3, but of course I am hopeful it is 5.

Most people think its 3 and/or 4.

 

I think we will know if the answer is 3 or not by spring.  This will also be around the time when heales.org plans to publish it's 'interim' findings, which will include S. Horvath's blood age measurements for both rat groups at 2 week intervals, which should be very revealing.


Edited by rodentman, 19 November 2021 - 11:35 PM.

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#164 QuestforLife

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Posted 20 November 2021 - 09:11 AM

I am a big believer in GHK-Cu, and I use it myself. But the results that came out from the first study, (and appear to be being repeated in this study) are so beyond the pale of anything else I've seen. Also, unlike the other the other epigenetic clocks, the GrimAge clock is difficult to 'fool'.

I think there are a few possibilities here:
1. E5 is a big hoax perpetrated by Katcher and S. Horvath.
2. E5 is a big hoax perpetrated by Katcher, as he was able to engineer rats with wildly different epigenetic tissue ages, and fooled S. Horvath into believing they were chronologically 25 months old.
3. E5 does reduce the epigenetic age of tissues by an average of 54%, and greatly improves the rats healthspan, but like nearly every other therapy, it 'peters out' as the rat reaches its programed max age, and doesn't significantly increase the rat's lifespan.
4. E5 can reprogram a rat's age, and extend its maximum lifespan indefinitely, but it won't work in humans.
5. E5 can reprogram a rat's age, and extend its maximum lifespan indefinitely.

1 & 2 seem very unlikely, based on the track record of both Katcher and Horvath.
My gut instinct is telling me 3, but of course I am hopeful it is 5.
Most people think its 3 and/or 4.

I think we will know if the answer is 3 or not by spring. This will also be around the time when heales.org plans to publish it's 'interim' findings, which will include S. Horvath's blood age measurements for both rat groups at 2 week intervals, which should be very revealing.

I hope it's 5 too!

Btw Horvath didn't use GrimAge; he used a pan tissue rat clock, a tissue specific rat clock, and a pan species human-rat clock.

The point I'm trying to make though, is that Katcher is a programmer and theoretical aging lecturer. He didn't have a lab and wouldn't have had the resources to discover something new. Based from his papers, Katcher would have tried one of the blood borne molecules that declines with age. Something like GDF11, Oxytocin, melatonin, Klotho, GrH, GHK, etc. He has denied it is GDF11 when questioned and we know Akshay is a big fan of GHK-Cu.

Whether or not E5 is GHK, it will be something like that. And Harold and Akshay, whilst they deserve credit for discovering its power over methylation (which they didn't anticipate, btw), are basically perpetrating a different sort of fraud from the scientific ones you discuss - a kind of financial fraud.

They could have just told everyone what is was, including fellow anti-aging enthusiasts they'd be corresponding with for years. But they decided to call in the lawyers, try and patent the use of a natural blood born molecule (or molecules), and make alot of money - plus delay it's therapeutic use in humans by years.

Edited by QuestforLife, 20 November 2021 - 09:13 AM.

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#165 albedo

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Posted 20 November 2021 - 06:23 PM

There was a (positive) comment by Vince Giuliano on Harold's work at 01:34:35 in this nice presentation today by Vince and Steve Buss (Steve writes in this Forum) on Triggering Ancient Mechanisms for Rejuvenation, an event chaired by David Wood:

 


Edited by albedo, 20 November 2021 - 06:24 PM.

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#166 ortcloud

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Posted 20 November 2021 - 07:41 PM

Yeah that's what's been claimed.

I am just putting forward the hypothesis that E5 itself is also GHK-Cu or even just plain GHK.

 

Dr Katcher confirmed E5 is not GHK or the ingredient in "blue gel" in latest interview

 

On a side note, he now admits he didnt invent it and asked the inventor (who he does not name but is loren pickart) for permission to use it.

Not sure how you get a patent on it though.

 

https://youtu.be/_NmSRSBqfTs?t=79


Edited by ortcloud, 20 November 2021 - 07:46 PM.

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#167 p75213

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Posted 21 November 2021 - 12:36 AM

Dr Katcher confirmed E5 is not GHK or the ingredient in "blue gel" in latest interview

On a side note, he now admits he didnt invent it and asked the inventor (who he does not name but is loren pickart) for permission to use it.
Not sure how you get a patent on it though.

https://youtu.be/_NmSRSBqfTs?t=79


What is the timestamp in the video where he says Elixir is not GHK? I watched it a couple of times and failed to hear even a mention of GHK.

#168 QuestforLife

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Posted 21 November 2021 - 08:17 AM

What is the timestamp in the video where he says Elixir is not GHK? I watched it a couple of times and failed to hear even a mention of GHK.

He evades mentioning GHK or Pickart. But he's as much as admitted the blue gel is GHK-Cu to anyone who knows what it is - lives in the blood stream a very short time, known for healing properties, ability to remove wrinkles, etc. Claiming he and Akshay 'rediscovered' it is gilding the lilly; it's been in use as a skin serum for years and Pickart has been consistently publishing papers on it for decades.

So my top guess was wrong then - E5 isn't GHK-Cu - although it could be a related molecule.

What is it then? It can't be that hard to work out. I've mentioned some other possibilities above; GDF11 Katcher has ruled out. But there's Oxytocin, Melatonin,Klotho, gonadotropin releasing hormone,... Like most programmed aging enthusiasts, Harold talks about the hypothalamus a lot and the circadian rhythm. And the hypothalamus was one of the organs looked at by Horvath, which seems an unusual choice for him to make (Harold must have suggested it).

As the hypothalamus only had minor epigenetic rejuvenation from E5, possibly due to lack of penetration of the blood-brain barrier (many signalling molecules don't pass the BB barrier, like GDF11), and Harold and Akshay are unsure how regular doses of E5 will have to be - this suggests looking at hypothalamic related proteins might be a good place to start.

Edited by QuestforLife, 21 November 2021 - 08:19 AM.

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#169 Harkijn

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Posted 26 November 2021 - 11:26 AM

As for the blue gel, it can be pre-ordered now. It turns out to be transdermal GHK.

https://www.neel.bio...pical-gel-100ml


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#170 Kevinsan

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Posted 26 November 2021 - 11:57 AM

Sephora and others have similar products.

 

 

After the debut of the Taiwanese brand in 2004, it established a global presence at Sephora stores where one can find the iconic mask drenched with the equivalent of an entire bottle of serum.

The Hyaluronic Acid GHK-Cu Moisturising Serum and Bio-cellulose Mask as well as lotion are upgraded formulas in the hydration series featuring Water-Activating Circulation Technology.

 

GHK-Cu refers to copper peptide, whose antioxidative property helps counteract skin damage caused by environmental aggressors. The new formulas also contain copper-rich malachite extract and marine collagen as anti-ageing components. The bio-cellulose mask is claimed to offer skin affinity allowing a deeper penetration and better absorption of the skincare ingredients. Made of fibres measuring only 20 nanometres in diameter, the material undergoes a reserved bacterial fermentation taking 15 days of mass and density build-up for a 3D nanostructure in order to achieve a sufficient downward pressure to "push" the serum into the skin.

 

https://www.sephora....-3pcs/v/7-masks


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#171 albedo

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Posted 26 November 2021 - 06:32 PM

Maybe you can help me in the context of the discuss of what E5 is.

In Harold's book you have a sudden sentence which intrigued me as was a bit out of the context of the rest of the text:

"Apparently, my string of somewhat strange guesses had proven correct. It was probably a good thing that I didn’t know Big Pharma spent millions trying to track down an E5-equivalent and failed. Anyway, it was a shot in the dark based on a limited understanding, but it proved better than understanding incorrectly, if I was right."

Does it mean, generally, all tries of producing a real anti-aging pill have failed or is he pointing to some industry specific molecule, similar to E5 in its mechanism of action, which failed? I tend to interpret as the former.


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#172 QuestforLife

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Posted 26 November 2021 - 09:16 PM

Maybe you can help me in the context of the discuss of what E5 is.
In Harold's book you have a sudden sentence which intrigued me as was a bit out of the context of the rest of the text:
"Apparently, my string of somewhat strange guesses had proven correct. It was probably a good thing that I didn’t know Big Pharma spent millions trying to track down an E5-equivalent and failed. Anyway, it was a shot in the dark based on a limited understanding, but it proved better than understanding incorrectly, if I was right."
Does it mean, generally, all tries of producing a real anti-aging pill have failed or is he pointing to some industry specific molecule, similar to E5 in its mechanism of action, which failed? I tend to interpret as the former.

I'm inclined to interpret it as the latter. He wasn't aware of failed attempts to locate the most important factor or factors in the blood responsible for the benefits of parabiosis, otherwise he might have given up before finding E5.

The incorrect understanding he refers to is the widely held belief that the body ages because it's cells age; his incomplete understanding was his guess at the clock or driving force of the inter-cell signalling that tells cells to act old.

Programmed aging has always been bedevilled by the lack of a smoking gun; the source or the clock that drives aging? What part of the body knows what 'life-stage' you are in and communicates it to the rest of the body?

In my reading I think I've identified the target to blockade to cause age-reversal: NF-kB. But the diverse range of inputs that stimulate NF-kB (some of which are also outputs) is overwhelming.

Somehow Harold found the silver bullet; an endogenous molecule that hit the right button hard enough to cause significant age reversal.

Edited by QuestforLife, 26 November 2021 - 09:17 PM.

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#173 aribadabar

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Posted 27 November 2021 - 02:33 AM

Elixir/E5 is GHK-CU or just plain GHK.

 

Discuss...

 

GHK-Cu is purple, GHK is white. So the blue gel can be the former and E5 can be the latter.

 

I am a big believer in GHK-Cu, and I use it myself.    But the results that came out from the first study, (and appear to be being repeated in this study) are so beyond the pale of anything else I've seen.   Also, unlike the other the other epigenetic clocks, the GrimAge clock is difficult to 'fool'.

 

I think there are a few possibilities here:

1. E5 is a big hoax perpetrated by Katcher and S. Horvath.

2. E5 is a big hoax perpetrated by Katcher, as he was able to engineer rats with wildly different epigenetic tissue ages, and fooled S. Horvath into believing they were chronologically 25 months old.

3. E5 does reduce the epigenetic age of tissues by an average of 54%, and greatly improves the rats healthspan, but like nearly every other therapy, it 'peters out' as the rat reaches its programed max age, and doesn't significantly increase the rat's lifespan.

4. E5 can reprogram a rat's age, and extend its maximum lifespan indefinitely, but it won't work in humans.

5. E5 can reprogram a rat's age, and extend its maximum lifespan indefinitely.

 

1 & 2 seem very unlikely, based on the track record of both Katcher and Horvath.

My gut instinct is telling me 3, but of course I am hopeful it is 5.

Most people think its 3 and/or 4.

 

I think we will know if the answer is 3 or not by spring.  This will also be around the time when heales.org plans to publish it's 'interim' findings, which will include S. Horvath's blood age measurements for both rat groups at 2 week intervals, which should be very revealing.

 

My vote is for a mix of 2 and 4. These guys are too cagey for be taken at their word and even if they achieved anything real , it won't work as well/at all in humans.

 

If they do mention Pickart in any way, shape or form, it's GHK/GHK-Cu. The guy is not known for anything else.



#174 JamesPaul

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Posted 27 November 2021 - 04:07 AM

A couple things:

 

1.  I thought I read somewhere that E5 was not just one substance, but a mixture of four "young blood" factors.

 

2.  The email that was sent out yesterday to people who signed up on the NTZ site to receive emails says the following:  "[Dr. Harold Katcher:]  GHK is used in all the high-end cosmetics, in famous brands...

"our formula...improves permeation to all the dermal layers and transdermal delivery. This solves the problem of the short half-life, and our upcoming product NEEL patch will be able to maintain optimum levels of GHK in us 24/7 to get the maximum benefit.

"We've proven this in vitro, with artificial skin, and then seeing how far it penetrates. But more than that, I tried it for almost a year. And the first effect that really impressed me is that I had actinic purpura on my arm. So, I applied it to my arms, and the standard recipe is twice a day for two weeks. And sure enough, my actinic purpura disappeared...

"But more than that, I felt better, I felt energy. What before had been a slog, where every step was like pushing myself further, became a walk, and sometimes even pleasant. And finally, when I came home, being in Utah, rather than Mumbai — I have a sort of home there too, and good friends — the walk from my carport to the back of my house, through my yard, which had previously been like a trudge, became a walk, just a stroll, just nothing of any significance. And you guys don't know because you're not old.

 

Nicolas Chernavsky, the interviewer, said "If GHK is so good in all aspects as you described, the reason the industry — the pharmaceutical industry, the cosmetic industry — didn't develop a way to deliver it through the skin seems to be that they didn't invest enough."

Harold:  "The cosmetic industry had no reason to do it. The fact of the matter is you can show that GHK will penetrate through the stratum corneum, the thick layer of the skin that prevents things from entering in, but slowly. It's good enough for skin, however, because you only have to go through a fraction of a millimeter to get to the base layer of the skin cells at the bottom of the epidermis."

 

NC: So the beneficial effects of the NEEL gel are not just for the skin...

HK: Right!
NC: ...because if it were just for this skin...
HK: There are one million products out there for that.
NC: Yes, exactly. This is important.
NTZ: So it's like a systemic action, but that you apply it through the skin to get this systemic effect.
HK: The skin or, as I mentioned, I applied it to the roof of my mouth. And you can apply it to any mucous membrane, to uptake it into the systemic circulation. And this is generally regarded as safe. It's already a constituent of humans, and there's never been shown to be any harmful level of it.
NTZ: You said the half-life in the blood is like half an hour. Do you think this happens because there is some kind of homeostasis to keep the concentration at a specific level?
HK: Sure.
NTZ: OK, so probably there is a system that the body has to maintain a certain concentration of GHK.
HK: Yeah, I'm sure. And I'm sure it's age-dependent.
NC: So the aim of NEEL gel is not only the skin but a systemic effect to reverse a bit a set of health problems?
HK: We don't know how much effect it has and we're looking for volunteers now.
HK: A product that makes money and we will forget about E5? No. E5 is our goal. NEEL gel is a boon to the elderly, but it won't reverse their age. It may make them healthier. It may make them more fit. It may make them more capable, but it won't make them young again. It may reduce their wrinkles, yes, and increase their endurance, etc. But they won't be young men again or young women again.
NC: OK, because I fear that if people see that Yuvan launched a product that is, let's say, similar to many other products in the market...
HK: If it were similar, we wouldn't have marketed it. The fact that we have, so that it enters your body and does deep healing, not just the superficial healing, that you don't have to inject it, which nobody wants to do, makes it a product that goes from a bizarre case of self-hacking to a legitimate product that will help people.

...

HK: ...I want to make it very clear that [the NEEL gel] has nothing whatsoever to do with E5. I mean, as far as I know, E5 may cause its increased production, that's certainly a possibility, but E5 permanently changes the age phenotype and the epigenotype of cells. This, I don't know if it does. Actually, this is an interesting question I'd like to answer myself with Steve Horvath's help. But having used it for a year, I found it very beneficial, but I still don't look like I'm 21.



#175 albedo

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Posted 27 November 2021 - 11:09 AM

I'm inclined to interpret it as the latter. He wasn't aware of failed attempts to locate the most important factor or factors in the blood responsible for the benefits of parabiosis, otherwise he might have given up before finding E5.

The incorrect understanding he refers to is the widely held belief that the body ages because it's cells age; his incomplete understanding was his guess at the clock or driving force of the inter-cell signalling that tells cells to act old.

Programmed aging has always been bedevilled by the lack of a smoking gun; the source or the clock that drives aging? What part of the body knows what 'life-stage' you are in and communicates it to the rest of the body?

In my reading I think I've identified the target to blockade to cause age-reversal: NF-kB. But the diverse range of inputs that stimulate NF-kB (some of which are also outputs) is overwhelming.

Somehow Harold found the silver bullet; an endogenous molecule that hit the right button hard enough to cause significant age reversal.

Thank for you interpretation! I am not convinced yet but of course you might be well right.

On NF-kB I feel you are absolutely on something even only looking at his results on IL-6 and TNF-alpha. He goes at length explaining how this transcription factor is responsible for IL-6, generate high level of ROS, is very harmful when binding to DNA generating senescent cells, inhibiting apoptosis and inhibiting Nrf2 (actually the latter is also mutual).

I am only tangentially interested to the guess work about what is E5, I wait for the results on humans but I am definitively impressed. Waiting also to understand a convergence on the principle of rejuvenation (OSKM (or à-la-Sinclair OSK), metabolic, senolyltics,  etc...) I will surely look how I can get an hand on E5 ... :)



#176 QuestforLife

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Posted 27 November 2021 - 12:26 PM

Thank for you interpretation! I am not convinced yet but of course you might be well right.
On NF-kB I feel you are absolutely on something even only looking at his results on IL-6 and TNF-alpha. He goes at length explaining how this transcription factor is responsible for IL-6, generate high level of ROS, is very harmful when binding to DNA generating senescent cells, inhibiting apoptosis and inhibiting Nrf2 (actually the latter is also mutual).
I am only tangentially interested to the guess work about what is E5, I wait for the results on humans but I am definitively impressed. Waiting also to understand a convergence on the principle of rejuvenation (OSKM (or à-la-Sinclair OSK), metabolic, senolyltics, etc...) I will surely look how I can get an hand on E5 ... :)


I am not saying I definitely believe in programmed aging (though I'd like to), only that is what Harold believes. So if we want to work out what he did, we have to think like him...
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#177 albedo

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Posted 27 November 2021 - 04:38 PM

Another question on E5 results: why Katcher does not report results on changes (if any) on IGF-1? I have always though about it also as a potential modulator of longevity. He mentions this in his book commenting on the results at Harvard (Fontana/Stroustrup) and it would have been easy to measure that in the E5 experimental set up. Or not? Am I overlooking something key? I realize study targets might have been different though.


Edited by albedo, 27 November 2021 - 04:50 PM.


#178 QuestforLife

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Posted 27 November 2021 - 05:23 PM

Another question on E5 results: why Katcher does not report results on changes (if any) on IGF-1? I have always though about it also as a potential modulator of longevity. He mentions this in his book commenting on the results at Harvard (Fontana/Stroustrup) and it would have been easy to measure that in the E5 experimental set up. Or not? Am I overlooking something key? I realize study targets might have been different though.


IGF-1 reduction is a measure of longevity, not rejuvenation. If you were to somehow trigger rejuvenation it may well INCREASE IGF-1 temporarily. Remember Harold doesn't think slowing aging is particularly useful, as you just extend all life stages. He is all about resetting the biological age right back, from which point you'd continue aging (ideally at the same rate as before).
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#179 albedo

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Posted 27 November 2021 - 06:29 PM

IGF-1 reduction is a measure of longevity, not rejuvenation. If you were to somehow trigger rejuvenation it may well INCREASE IGF-1 temporarily. Remember Harold doesn't think slowing aging is particularly useful, as you just extend all life stages. He is all about resetting the biological age right back, from which point you'd continue aging (ideally at the same rate as before).

I understand your point and fully stand with you re the target intervention but wouldn't that very same fact that IGF-1 might have well be increased temporarily be enough reason to also include it in the panel of all markers they tested? I would not have included if I had no clue of how to interpret a result one way of the other, but surely he does. I am not convinced why that was not included.

 


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#180 QuestforLife

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Posted 27 November 2021 - 07:54 PM

I understand your point and fully stand with you re the target intervention but wouldn't that very same fact that IGF-1 might have well be increased temporarily be enough reason to also include it in the panel of all markers they tested? I would not have included if I had no clue of how to interpret a result one way of the other, but surely he does. I am not convinced why that was not included.

Fair point, but they did the rat experiment on a shoestring - Akshay paid for it. Only later did they get Steve Horvath involved and since his results (,which everyone knows about) they now have more options (and budget). So maybe they'll measure more biomarkers in the current aging study. And after all we won't care about biomarkers if those rats live past their max age.

And can I just add - I'm so glad they did all this with rats. A much better lab species than mice.

Edited by QuestforLife, 27 November 2021 - 07:55 PM.

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Also tagged with one or more of these keywords: aging reversal, epigenetics, dna methylation clock, heterochronic parabiosis, programmed aging

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