Introduction to Young Plasma Infusions
Just to clarify for everyone what the phrase "young plasma infusions" refers to:
Plasma is the water portion of blood in which blood cells are suspended. It includes salts, proteins, hormones, and many other non-cell components.
The idea of transferring young plasma into older people for the purpose of rejuvenation is at least somewhat related to studies of parabiosis, which found that when an old mouse shares the circulatory system of a young mouse, the old mouse appears to get younger (and the young mouse appears to get older, by some measures).
The thinking here is that there are components in the blood--possibly non-cell components such as hormones and signaling factors--that affect health and rejuvenation capacity.
One way to replicate these possible positive effects of non-cell components of young blood is to infuse older people with plasma from younger people. Plasma donation and infusion are common and standardized medical procedures, so it does not need special development or approval like a new pharmaceutical does.
At least one company is providing this service commercially: Ambrosia. As of this writing, their website is not functioning properly.
It would be interesting to many members of this group if anyone receiving young plasma would share their experiences in this section of the forum. If you'd like to share your story, I invite you to click "start a new topic" on the right side of the forum page in this section.
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"Elixir" Resets Horvath's Clock
This is the work being referred to above. A preprint was recently placed on BioRXiv at https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1 , authored by Steve Horvath, many others, and in particular Harold Katcher and Akshay Sanghavi, the founders of Nugenics Research of Mumbai, India They report an experiment in which they use "Elixir", a Nugenics proprietary combination of active ingredients extracted from the blood plasma of young rats. They administer Elixir to old rats, and observe the effects on various biomarkers of aging, including Horvath's famous DNA methylation profiles. The results are spectacular, showing that the DNA methylation profiles were reset in age in various tissues ranging from liver to brain and other biomarkers showed similar results. A popular account of the paper is available at Longevity Technology.
I am very surprised by these results. I had previously argued that periodic injections of young plasma could not be expected to do much because the active agents could only be resident in the recipient's bloodstream for a day or so, and any beneficial effect would be transitory at best. These experimental results indicate that this is not the case. The effects on rats last well after the treatment period and seem to be permanent. Therefore, I'm puzzled. I don't understand the mechanism.
I asked Harold Katchner about this. He would only say that my assumptions were wrong, but implied that he was unable to explain why and how for trade-secret reasons.
If anyone understands how brief exposure to the active agents in a derivative of young plasma can produce long-lasting effect, please explain it to me.
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Fred Cloud
Yes. But he won't before they do animal tests. Their plan is to get $50M of venture capital and set up a branch in California that rejuvenates dogs and cats. They don't need FDA approval for that, just a cooperative vet.
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JGC Interesting. Well Josh said "Katcher is committed to bypassing the standard channel of Big Pharma, proceeding on his own with appropriate partners to assure that the the technology gets to a wide public at affordable prices" Why not set up in mexico or panama etc and offer it to humans? I say he should set up shop next to Dr Riordan at the stem cell institute in panama.
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JGC Seems so complicated and unnecessary. Why not bypass all of that and go offshore? There are alot of unproven therapies offered now like stem cells and people pay top dollar and flock to place like riordan in panama and pay $25k. So he actually should forget all the partners and funding and california regs. and set it up himself offshore and offer it to humans now and then create the study with the humans using it. He might need a million at most and he can be helping people sooner, cheaper and easier.
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JGC if you go https://twc-stanford.shinyapps.io/aging_plasma_proteome/ you can enter a gene/protein in the blood and see level of changes with aging. There is about 2925 proteins associated with aging captured in that database. The ones that you would want to promote, increase levels of, as there are much higher levels associated with young blood are growth differentiation factor 15 GDF15 and RET. The ones who you want to demote or decrease levels of are: SCARF2, SOST, ADP Ribosylation Factor Interacting Protein 2 (ARFIP2), PTN, IGDCC4, MLN, and CGA. The list is pretty exhaustive so whatever protein is in elixir is most likely captured by that database already. of Also GDF-11 levels are pretty constant with age so it doesn't look like it matters much. So what does he say about what is in elixir? If I were to experiment I would up the dose of promoters and filter out demoters and apply it to marmosets to properly establish dose and schedule.
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Joe smith I dont think that is what the elixir approach is. I think it is a dna demethylase enzyme that acts to scrub off the methylation on the dna directly.
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JGC sounds good. I’d be shocked if they didn’t. Further I suspect that they are the protagonists.
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I just looked up the size of TET1, which is the smallest of the three TET proteins. It has a mass of 80,000 Daltons (which we physicist call 80,000 AMU). I think that's much too big to get past the cell wall, so I'm not sure that having it resident in the bloodstream would do anything. A link to picture of TET1 is below.
On the other hand, one can buy 10 micrograms of TET1 for $188. Does anyone want to try shooting up some?
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JGC yeah tet proteins are actually very large ~180-230-kDa. What I was trying to say is that high 5hmC in young blood restores tet2, which in turn binds to dna and demethylates. See attached pic illustration.
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Joe smith JGC How about Kdm4 (Jmjd2/Jhdm3) as a demethylase? Not sure the atomic weights.
The histone lysine demethylase 4 (Kdm4/Jmjd2/Jhdm3) family is highly conserved across species and reverses di- and tri-methylation of histone H3 lysine 9 (H3K9) and lysine 36 (H3K36) at the N-terminal tail of the core histone H3
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Fred Cloud
KMD4A is pretty big, around 130,000 Da, and I think it would be difficult to synthesize (which Katcher claims he can do). Therefore, I doubt that it is a component of Elixir. It does seem to have the capability of removing methyl radicals from DNA, but I think a proper epigenetic reprogramming would require rearrangement (not simply removal) of the DNA methylation. Here's a picture of KMD4a:
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JGC Interesting. Not sure if you have read Vince Giuliano writeup on his guess of what Katcher is using but it is a fascinating read. He speculates that it is JMJD2/JMJD3 but like you said it might be too big.
You could email him and ask him about the dalton size issue, he answers his emails and is the nicest guy. I will PM you his email address.
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Fred Cloud
I just read two of his YOUNGING1.0 blog posts. I would have thought that if his age-reversal assertions about dementhylating histones are correct, it would have shown up on the Horvath DNAm Age test that he took.
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Interesting point JGC, Is TET1 found circulating in plasma or does it just exist intracellularly? Because if it isn't found in plasma then would we be able to eliminate this as a possibility of the active ingredient in Elixir. (assuming Katcher is being forthright about this being a plasma fraction.)
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There is an interesting article about Harold Katcher's "Elixir" experiment (unknown young-rat plasma fraction rejuvenating old rats) that was posted last June on LongeCity. It includes comments on the work by David Sinclair that I had not previously seen. Here's the LINK.
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JGC Great article, thanks for posting. I did read Sinclairs comments before, I think he posted it on Twitter back when this was released.
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JGC What do you think of this article "Diluting blood plasma rejuvenates tissue, reverses aging in mice" which seemed to achieve similar outcomes without any young plasma fraction? Blood plasma was swapped with a solution of saline and albumin.
https://medicalxpress.com/news/2020-06-diluting-blood-plasma-rejuvenates-tissue.html
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Dan Nave
That is the work of Prof. Irina Conboy's group at UC Berkeley. It's good stuff, and it can probably be put into practice without a lot of FDA red tape. See the discussion at Recent Plasma-Replacement Results.
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