236 replies to this topic

[kurt9]

I think the peer review process is overrated. The acid test is other researchers being able to reproduce the results.

 

In any case, I do not consider aging as an epigenetic process as incompatible with SENS. SENS describes specific damage mechanism. Yes, it proposes various methods to fix that damage. But if epigenetic reprogramming can fix many of these damages, then it should be considered a part of SENS strategy. There may be some damage that may needed to be fixed by other SENS approaches such as AGE crosslinks, particularly in the extracellular matrix. A close friend of mine believed this to be a red herring as he believed that the protein glycogen  crosslinks were due to nothing more than an imbalance between anabolism and catabolism, and that restoring such balance ought to clear up those crosslinks. He did think that some of these might have to be removed by a SENS-like approach.

 

Something that has been very clear to me even since I became interested in life extension is the inherent dynamism of biological systems. One of the problems of conventional medicine is its "civil engineering" approach to biology, which assumes it to be a static structure like a car or a building. That biology is dynamic is our friend because it means that aging, in principle, is entirely reversible.

[Raphy]

I didn't want to belittle the work of the SENS foundation in any way, and I think their program is a very good plan especially when we know so little yet about the aging process. We are all in the same boat, and Aubrey De Grey would certainly never mind where the breakthroughs come from.

 

And it doesn't matter if the study from Harold Katcher turns out to be a fake. There is now enough evidence that epigenetic reset clears multiple hallmarks of aging that we should bring a lot of attention to it. And if the cells know how to be young whatever the organism age, it means there are signals in its environment that regulate its phenotypical age. And parabiosis experiments confirm that. 

So whatever happens with this particular study, anti-aging therapies should prove much easier to develop than the SENS's program initially envisioned. So technology wise I am very optimistic. The main hurdles will likely be the rest of society, their regulations and prejudices.

 

By the way I am sure your friend is right re extracellular matrix turnover. 

Edited by Raphy, 26 June 2020 - 02:31 PM.

[albedo]

In case you missed it, also discussed here:

 

https://www.longecit.../nugenics2020a1

https://www.longecit...nugenics/page-2

 

(edit: adding link)

Edited by albedo, 02 July 2020 - 03:06 PM.

[Michael]

Unless someone objects, I'm going to merge this thread with this one.

[albedo]

Unless someone objects, I'm going to merge this thread with this one.

Ok to me, tks

[Raphy]

Anyone is trying to reverse engineer this? How would you go for that? How would you go from the logical conclusions that something in the young plasma rejuvenates the organism and/or age it, to finding out which factors?

 

Considering the time frame under which they developed their plasma fraction, their can't be a lot of factors involved?

 

This article might be of interest to start https://joshmitteldo...-fraction-cure/

 

 

Our first pass was to try a combination of known herbal supplements that are known to bind with the targets we’d identified.  We gave them to rats, and at first nothing seemed to be happening. But after two months (about 4 years in human terms) the rats showed signs of rejuvenation.  We were encouraged. Rather than continue with the herbs, though, we formulated the elixir that we report on here. This is our first iteration, with dosage and timing determined theoretically, yet to be optimized in the lab.

We have addressed several different problems:

1. Identification and purification of youth-inducing factors and a process for their large-scale production. Our processes are scalable from microliters to metric tonnes
2. Raw material supply: we have gone beyond the need to obtain blood from young people, our sources are virtually limitless
3. Removal of the effects of ‘pro-aging-factors’.  We have discovered a way to do that, one hidden in plain sight.

 

[albedo]

A couple of updates for Josh's blog:

 

"Hi All happy to send the photo if you could please share your email id the way Ross did.
We have already formed our US company. Finalized our Lab premises in California. Hope to file patents in Sept/Oct. Hope to have a first close of early investors for our convertible round in Sept/Oct. We have been waiting since April to start our dog trial in California but pandemic continues to block the assembly of our team there. Once our round closes we plan to start manufacturing the gel. This could be available on Amazon around Christmas if we are lucky. We have also found a contract manufacturer in USA for the transdermal version but that requires FDA nod so can’t predict by when we can ship that. May be first quarter next year. We have used the time to discuss with various experts about our clinical path with FDA and this will help us speed up our trajectory towards Phase I human trial. We are hiring a very senior regulatory officer. Wish us luck."

"We would have completed our old dog and marmoset studies but due to the pandemic we are delayed. We are using the time to complete our IP filings worldwide. We will update you as soon as we can launch our trials."

(Akshay Atomic Bliss)

 

"This was released today by Alkahest. More akin to what the Conboy’s are doing:

“Alkahest’s preclinical research has demonstrated that Beta-2 microglobulin, which is present at higher levels in older individuals, is drastically elevated in patients undergoing dialysis and may contribute to the high prevalence of cognitive impairment in these individuals. By reducing the amount of B2M in the plasma, we hope to introduce an effective way to lessen this impairment and allow patients on hemodialysis for ESRD to achieve improved treatment outcomes and quality of life [2].”"

(Larry)

 

https://joshmitteldo...rough/#comments

 

Edited by albedo, 25 August 2020 - 06:13 AM.

[RWhigham]

Thanks albedo!  More from Josh Mitteldorf's "Age Reduction Breakthrough" blog

 

May 11, 2020   Akshay Atomic Bliss

"We have two separate products: one is a very powrrful anti aging molecule already tested on Harold with amazing effect (all his aging spots from his arms disappeared in a week). This product we wish to sell as a topical gel and transdermal patch. The gel will fall under cosmetic category with FDA so may be out early. Patch needs a FDA clearance so may take longer. Apart from this is our flagship product code named Elixir which would be administered as injections or IV."

 

May 13, 2020  Harold Katcher

Harold responding to "does the gel have systemic effects:"  ".. it seems that the effects of blue stuff are considerably more than skin deep. I’m not here to advertise anything, but it seems to affect my coordination and had hair grow back on my scalp and I no longer apply it to my skin."

 

August 6, 2020  Akshay Atomic Bliss

"We have been working on our IP and should complete filing soon but the details wont be out for 18 months. Our planned dog trial would have completed by now but due to the pandemic it is delayed. In the meanwhile we are working on adding more trials of larger animals after pre-IND discussions with FDA."

 

August 24, 2020  Akshay Atomic Bliss

Newest info quoted above by albedo

Edited by RWhigham, 25 August 2020 - 04:30 PM.

[Daniel Cooper]

As an aside, I think referring to their product as an "Elixir" is a tactical mistake.  It gives it a whiff of P.T. Barnum.

 

 

[bosharpe]

So are the patch & gel products based on the plasma fraction technology or are they the 'herbal mix'?

[RWhigham]

So are the patch & gel products based on the plasma fraction technology or are they the 'herbal mix'?

The plasma fraction "Elixir" is injected directly into the bloodstream where it tells the entire body how old its supposed to be--with the Elixir it is young. The Elixir is comprised of a collection of signaling "things" (molecules, mRNA, proteins or whatever). The signaling "molecules" in blood have been researched for many years now--ever since the hetero-chronic parabiosis experiments showed that blood strongly affects age. The number of possible signaling "molecules" in blood is in the many many thousands, and except for Harold very little progress has been made figuring it out. Harold made an informed but lucky guess, and has serendipitously leaped past the entire rest of the world.

 

The gel and patch are based on "a powerful anti-aging molecule" (per Akshay above) and may or may not be one constituent of the Elixir. It will not be revealed until patents are in place.

 

Ever since he saw the heterochronic parabiosis results Harold has been convinced that a creature's blood times its life and death cycle, eventually ending its life on purpose tor the good of offspring. So he has thought about it and read the literature for a long time.

 

Edited by RWhigham, 27 August 2020 - 06:33 PM.

[p75213]

Is the elixir a natural product or a new drug? I remember reading somewhere the anticipated release date is a year or two.

[RWhigham]

Harold Katcher comments:  (excerpts from Josh Mitteldorf's blog)

 

"if nothing else, I can definitively say that chronic inflammation due to aging can be reversed with factors present in young blood.

 

"if SOD decreases as we age that exactly comports with what we observed. Only in Elixir-treated animals did SOD increase. In untreated old rats it decreased.

 

"This is not based on ‘theory’ (say mitochondrial aging or ‘wear and tear’) but on experimental evidence. Theory comes in explaining our results, not achieving them,

  

"There is much to do, and the basic principles will create a new branch of biology (rejuvenation science).

 

"eventually, everyone will use it.

 

"being 75 myself puts a time-frame around the project.

 

"It will end up changing humanity.

 

"what will people do with those extra years (decades, centuries, millenia

 

"I dreamed that somehow in the far future (and on another world), I was being feted for ‘bringing immortality to mankind'

 

"It is my own belief that man will travel, immortal in the heavens, sail to the distant stars. There are infinite possibilities if you worship life, not death."

Edited by RWhigham, 30 August 2020 - 03:12 AM.

[albedo]

Thank you RWhigham. Reading his vision I wondered if he signed for cryonics. Anybody knows? Just curious.

[bosharpe]

The plasma fraction "Elixir" is injected directly into the bloodstream where it tells the entire body how old its supposed to be--with the Elixir it is young. The Elixir is comprised of a collection of signaling "things" (molecules, mRNA, proteins or whatever). The signaling "molecules" in blood have been researched for many years now--ever since the hetero-chronic parabiosis experiments showed that blood strongly affects age. The number of possible signaling "molecules" in blood is in the many many thousands, and except for Harold very little progress has been made figuring it out. Harold made an informed but lucky guess, and has serendipitously leaped past the entire rest of the world.

 

The gel and patch are based on "a powerful anti-aging molecule" (per Akshay above) and may or may not be one constituent of the Elixir. It will not be revealed until patents are in place.

 

Ever since he saw the heterochronic parabiosis results Harold has been convinced that a creature's blood times its life and death cycle, eventually ending its life on purpose tor the good of offspring. So he has thought about it and read the literature for a long time.

 

Thanks, yeah I saw those comments. Here's hoping the gel IS based on the Elixr.

[RWhigham]

Harold Katcher  "I would like to extend life – by rejuvenating people over and over, each time giving them a new youth coupled with old and deep knowledge. living an extra fifteen or twenty years won’t make much differences to us if our best years are behind us, but with rejuvenation, our best years will be ahead of us, the plasticity of the young brain coupled with the life experience of the old, even the older-than-have-ever-lived-before, what a combination that would be."

Edited by RWhigham, 04 September 2020 - 11:42 PM.

[zorba990]

In terms of taking another step back to identify root cause here:
What part of the body is supposed to be making these young blood factors, such that it is failing to produce them at 'young' age levels?
Does adding these factors back in further atrophy this mechanism such that a dependency would be created?
Is there any evidence of rapid reversal of the effect once the exogenous factors are taken away

Edited by zorba990, 05 September 2020 - 08:18 PM.

[RWhigham]

Does adding these factors back in further atrophy this mechanism such that a dependency would be created?

Is there any evidence of rapid reversal of the effect once the exogenous factors are taken away

See Reversing age: dual species measurement of epigenetic age with a single clock. Scroll down and look at the figures, they show the rats for 151 days post treatment getting younger the whole time. Excerpted from the article"The plasma fraction treatment system employed here has been tested several times with reproducible success. In addition to improvements in clinical markers of aging, our work shows, for the first time, that plasma fraction treatment also reduces considerably, the epigenetic age of multiple tissues. It is evidently very effective in rejuvenating several tissues in old rats; requiring only two series of injections. The rejuvenation of non-blood organs from this intravenous treatment, coupled with reversal of the epigenetic clock within these organs supports the notion that aging can be systemically controlled,"

In terms of taking another step back to identify root cause here:

What part of the body is supposed to be making these young blood factors, such that it is failing to produce them at 'young' age levels?

Every cell in your body has the needed information in the DNA library The DNA just has to be epigenetically reprogramed to start expressing the right proteins. In theory, it could come from everywhere.

Edited by RWhigham, 05 September 2020 - 10:55 PM.

[Engadin]

.

 

 

 

BTW, Grifols to acquire 100% Alkahest to enhance discovery research and development to identify innovative therapies for age-related diseases based upon an understanding of the human plasma proteome.

 

From Grifols webpage:

 

"Bioscience

 

With the largest network of plasma donation centers in the world, the Bioscience Division is a leading producer of plasma-derived medicines for the treatment of rare, chronic and sometimes life-threatening conditions.

 

To help ensure a reliable, consistent source of plasma medicines worldwide, we have an all-inclusive process that begins with plasma collection and continues through fractionation, purification and production.

 

 

 

Plasma proteins

 

• Immunoglobulins, particularly intravenous immunoglobin (IVIG) in immunology. Used mainly to treat primary immunodeficiencies and chronic inflammatory demyelinating polyneuropathy (CIDP), a rare neurological condition.
• Albumin to restore circulating blood volume and protein loss in such physiopathological conditions as liver cirrhosis, trauma, cardio-circulatory insufficiency or severe burns. Research currently underway to assess its potential to treat Alzheimer's.
• Alpha-1-antitrypsin to treat alpha-1-antitrypsin deficiency, a rare genetic disease that can lead to severe lung diseases such as emphysema.
• Factor VIII and other clotting factors for hematology used primarily to treat hemophilia and other conditions that may result in bleeding episodes, including internal bleeding with subsequent tissue and organ damage.
• Other specialty hyperimmune immunoglobulins to treat potentially fatal infections such as rabies, tetanus, hepatitis B and Rh incompatibility.

 

Plasma quality and product safety

 

Plasma is the clear, liquid portion of the blood. About 90% is composed of water, while the remaining 10% contains hundreds of essential proteins. Without enough of one of these proteins, a person could have a life-threatening condition.

 

Donor health and patient safety are our top priorities. We ensure that all plasma donor centers are held to the highest quality and safety standards established by US and European health authorities.

 

Plasma collection is performed in highly controlled environments by professionally licensed and trained staff. This allows us to maintain very high standards of quality and safety for the medications we produce."

 

 

 

In other words, Grifols, with Alkahest adquisition, reinforces its leadership on plasma-derived compounds market, probably and, if so precisely, including the production of the sort of blood components Elixir success is based on.

 

Looks like an interesting 'emerging market' (rejuvenating one?) move that might backup, somehow so far, Karcher's and team findings, IMHO. I would keep a close eye on this, because I suspect there is more to come sooner than later. Grifols is well known for very smart strategic actions up to now.

 

 

 

.

Edited by Engadin, 07 September 2020 - 11:16 PM.

[albedo]

An update by Akshay in Josh's blog:

"An Update:
Our Mumbai Lab has finally restarted and is moving fast. Our first trial next week would be to test lyophilized Elixir. Next trial will test double dose, female fertility and more which should launch in November. In this trial we will also be taking photos, videos and conduct third party medical test to confirm same old rat has become young. We will also prolong it for lifespan study. Our 2 year Dog trial work has restarted. We hope to launch in first Qtr 2021. We are working with attorneys, ranked in the top 10 in 2019 for biotech patents issued, from many months. It has taken this long as it is our foundational IP. We are in final stage, claims are shaping well. We should be able to file within a few weeks. So that will be a big relief. Our gel and patch both are moving as planned. Vendors have been identified and final product development work is being done. Followed by regulatory filings. Our marketing partner wants us to launch in Feb/Mar 2021 on Amazon USA. We are planning a human trial for gel and patch before launch for aging spots and wrinkles. We will share the results here with Josh. One of our supporters and investor who has background in biotech is leading the vendor development and management, QC, packaging shipping, etc. We have incorporated our USA co called Yuvan Research Inc. HQ in California. We have launched our SAFE funding round for early supporters to fund our preIND and IND work with FDA for Elixir. Many of you had shown interest to participate so you can reach me at: atomicblissventures at gmail dot com"

https://joshmitteldo...rough/#comments

(edit: add link)

Edited by albedo, 15 October 2020 - 12:15 PM.

[michael0505]

Thanks for the update. Not sure I like the name Yuvan Research

[zorba990]

Re : "Our marketing partner wants us to launch in Feb/Mar 2021 on Amazon USA. We are planning a human trial for gel and patch before launch for aging spots and wrinkles"
As awesome as that sounds, in what way would this not be considered a drug?

[smithx]

Re : "Our marketing partner wants us to launch in Feb/Mar 2021 on Amazon USA. We are planning a human trial for gel and patch before launch for aging spots and wrinkles"
As awesome as that sounds, in what way would this not be considered a drug?

 

it depends on the claims they make and whether the FDA wants to say anything about it
 

[albedo]

A short update today by Akshay in Josh's blog in response to a question:

Hello. How do your studies go? Are there any news? We stand with you, geniuses!

"...we have launched rat trials and the dog trial is slated to start in February 2021. We will update here within first few weeks with early results from blood draw after treatment..."

https://joshmitteldo...rough/#comments

(edit: link)

 

Edited by albedo, 05 November 2020 - 12:48 PM.

[albedo]

 

A short update today by Akshay in Josh's blog in response to a question:

Hello. How do your studies go? Are there any news? We stand with you, geniuses!

"...we have launched rat trials and the dog trial is slated to start in February 2021. We will update here within first few weeks with early results from blood draw after treatment..."

https://joshmitteldo...rough/#comments

(edit: link)

 

 

and a following additional update:

 

"... March April next year we are also getting ready to launch our first products: blue gel and transdermal patch. Currently technical work with vendors, regulatory lawyer and marketing team have been underway. We are also planning a human trial in Bay Area California which will be published in a peer-reviewed journal so if any of you are in BayArea you, your spouse and friends/relatives 55 years to 85 years of age are welcome to participate..."

 

https://joshmitteldo...rough/#comments
 

[Iporuru]

Studies financed by Heales: Effect of young rat plasma on the lifespan of aging rats

 

"The Heales organization decided to fund, with a rather modest but useful amount (2 times 25,000 dollars), two studies on the maximum longevity of these animals. One will be conducted by Professor Harold Katcher in his laboratory in India and the other is under the direction of Professor Rodolfo Goya at the Institute for Biochemical Research in Argentina

 

Based on the above information, we decided to evaluate the possible effect of the plasma of young rats on the lifespan of older rats (25 months). Specifically, we propose to compare the survival of older rats treated intravenously with young plasma with that of corresponding age controls (untreated). We also propose to collect blood samples from all animals, every other week, in order to follow the evolution of epigenetic age over time. As a functional assessment, we plan to evaluate the performance of spatial memory before the start of treatment and 3 months after. Cognitive tests will include an evaluation of motor performance.

 

To learn more about the protocol used in these two studies, here are the corresponding documents: 

Rodolfo Goya
Harold Katcher

[pone11]

Thanks. I've got a long first post-answer mostly done, just needs a bit of tweaking.

 

Two points for now...

• It's not blood donation. Katcher himself eliminated that as the explanation with these sentences.

Although transfusion technologies for humans are mature and quite safe, transfusing small animals requires state-of-the-art lab techniques. Try as we might, we could not perform plasma exchange in rats. Time was growing short (I was on a two-month visa) so what to do? I made the decision to completely change my approach: yes I believed HPE would work, but I decided to leap ahead, to see if we could make the process of HPE into a marketable product.

• Akshay's comment about bioavailability speaks to the question of dosing required to get an extraordinary response.

We used proprietary synergies and conjugates to improve bioavailability. Bioavailability cannot be highlighted enough

 

What does the quote from Katcher "yes I believed HPE would work, but I decided to leap ahead, to see if we could make the process of HPE into a marketable product." even mean?  How do you turn the "process of human plasma exchange" into a "product" when your previous sentence is that you could not do the animal equivalent of human plasma exchange?  It's an extremely obtuse remark.

[pone11]

As far as I know, at present, there is no experiment that shows definitively that Heat Shock is the most significant independent variable of the Katcher experiment.

 

Why do you keep talking about heat shock proteins?  Do you even understand that Katcher's study is claiming that they reversed epigenetic aging in almost the entire body of a rat?   And they made these changes last for what would be the equivalent of five or more years in human time from one treatment.   Where has anyone shown that heat shock proteins have even a slight ability to reverse epigenetic aging?     It's just a bizarre hypothesis you are making without introducing any evidentiary basis for making that connection.

 

I think the researchers told us in plain form what their hypothesis is:  they changed chemical signals in the blood that then caused cells to turn off their "old" methylation patterns and restore "new" ones.  heat shock proteins do not do that, at least not at this kind of level.

Edited by pone11, 31 December 2020 - 01:07 PM.

[pone11]

 
QuestforLife... I believe my post immediately above provides study links showing overwhelming evidence that one or more Heat Shock Proteins are implicated in the Katcher study findings.
 
This conclusion is almost certainly true also because the positive health and youthfulness impact of the Katcher experiment FITS with other evidence showing that Heat Shock Protein expression can have profound effects on Survival Probability.

 

Sauna and heat shock proteins affect cardiovascular outcomes because they improve blood flow and vascular endothelial function.   All cause mortality simply reflects the change to cardiovascular mortality.  Again, do you understand that Katcher's study is saying they reversed the aging of cells and they have a direct measurement of that with Horvath's new epigenetic clock for rats, measured in many kinds of tissues in those rats?    Where is there any experiment showing that when you flip the switch on epigenetic configuration for the genes that are responsible for producing heat shock proteins, or when you change HSP production levels, that an animal loses 50% of its cellular age?   It just feels like you are picking your favorite topic out of thin air and trying to somehow insert it into a theory where it just does not fit.

 

If you want to advance the argument that HSP reverse epigenetic age, then confront that specific question head on.  Where is the research showing that adjustments to HSP affect epigenetic age of specific types of tissue or blood?   Quantify it.  How long does it last?   Is there any experiment where they promote HSP production with a single treatment and the decrease in epigenetic age of any type of cell lasts for YEARS???

Edited by pone11, 31 December 2020 - 01:26 PM.

[pone11]

Guys, 

 

Is everyone out of their minds?
...

Two guys working without the support of an enormous lab and a giant network not just "isolate" or "identify" the factors in blood that lead to aging. 

Such an effort required en enormous amount of resources. Something similar was accomplished in Harvard by the lab of Amy Wagers -it is a monumental undertaking. 

These 2 people have identified the factors, have conducted experiments to reduce the concentrations in the blood, failed at that and devised another method (which was hiding "in plain sight") and also have pulled up the herbal supplements that bind with these targets???
 

Sorry, this is BS.

Each of those steps in isolation is beyond he scope of their ability. It doesn't matter how many literature reviews they write or what kind of nice guys they are

 

You have a right to be skeptical and I agree with some of what you say.   But do not forget that their paper has Steve Horvath's name on it.   Steve Horvath is a first rate scientist with incredible integrity and his epigenetic aging clocks are extremely important science.   Now the question is did the "two guys" pull one over on Horvath.   At this point there is not enough information made public to even speculate about that.   But Horvath has said he compared the DNA of each rat on the before and after samples, so if there was a fraud it was something clever and elaborate, and it passed the sniff test of one of the world's best scientists in DNA aging measurements.