Recent Plasma-Replacement Results

    Two recent results have been published that are worth reporting here and are recommended for careful reading.

    The first of these is a paper by Dr. Harold Katcher, Dr. Steve Horvath, and others reporting on a development originated by Nugenics Research of Mumbai, India.  The work was done on by applying a component of young plasma (given the name Elixir) extracted from the blood of young rats.  This Elixir was administered to aging rats, and measurements of the Horvarth methylation bio-age clock were done before and after the treatment.  The before and after clocks indicated that in blood, heart, and liver tissues the bio-age was reduced by a factor of two.  Less pronounced but significant clock-reduction was observed in the hypothalamus.

    The second paper is the work of Prof. Irina Conboy's group at UC Berkeley.  They examined the question of whether young-blood-produced tissue regeneration comes from the presence of beneficial components in the young blood or from the absence or dilution of harmful components in the old blood.  To do this, they replaced the plasma in the blood of aging mice with saline solution containing 5% purified albumin.  Unfortunately, they did not do bio-clock measurement on the results, but they noted beneficial effects to muscle, heart, and nerve tissues equal-to or exceeding those of young-old plasma exchange.  The implication is that the benefits of young blood may lie in the dilution of harmful components present in old blood.

    These are both preliminary studies using animal models, but their implications for us aging humans who could use some rejuvenation are very interesting.  The Conboy  results are particularly of interest because immediate application to humans would probably not encounter FDA roadblocks.  (FDA Experts: please comment!)

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  • The closest you can replicate this now without a doc and machines would be to donate blood a couple of times a year and take gdf11 at home. The next level would be to get a doc with a plasmapheresis machine and have him replace some of your plasma and buy some plasma from the ambrosia company. Speaking of, I wonder if these plasma doctors like ambrosia will offer some sort of plasma exchange as an extra option.

    Perhaps some docs will offer this as a standalone service much like the chelation docs back in the day would have rooms full of people in the IV room. The closest you can get to that now is In germany, they have lots of  plasmapheresis treatment centers where they will filter your blood and should be able to replicate the conboy effect. Much like chelation requires frequent treatments to maintain, I wonder how often you would have to do dilute your plasma to maintain results?

    Like
      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
      • Reported - view

      Fred Cloud Has anyone been to the Young Blood Institute? They offer Therapeutic Plasma Exchange.

      Lots of great info on their site

      https://youngbloodinstitute.org/aging--blood.html

      Like
      • JGC
      • JGC
      • 3 mths ago
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      Fred Cloud 

           In the case of the Conboy treatment, I don't understand why you suggest that one might need to "buy some plasma from the ambrosia company".   Googleing "plasmapharesis", I get this: "Plasmapheresis is a process in which the liquid part of the blood, or plasma, is separated from the blood cells. Typically, the plasma is replaced with another solution such as saline or albumin, or the plasma is treated and then returned to your body."  That's precisely what the Conboy group is doing with rats, replacing old the plasma in their blood with saline plus 5% albumin.

           My point is that there needs to be a trial in which this is done with old humans, with before-and-after Horvath methylation tests done to determine if there is any reduction in bio-age indicating rejuvenation.  Of course at least one MD needs to be involved, but since only saline and albumin are used, there should be no FDA issues.

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    • Fred Cloud and JGC--got something going here. Thank you both very much!!!!

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      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      JGC I suggested getting plasma from ambrosia to replicate both sides of parabiosis because they both have therapeutic effect, taking away the bad stuff (conboy) and adding young factors (Katcher, ambrosia, young plasma)

      But you are correct if you just want to solely replicate the conboy approach of taking away or diluting bad stuff and you only wanted half the benefit of parabiosis then you would only need the plasmapheresis.

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      • JGC
      • JGC
      • 3 mths ago
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      Fred Cloud 

           I think Harold Katcher's Elixir is rather different from (and more effective than) what you would get from Ambrosia, but since the Elixir contents are proprietary, I don't really know.

          You suggested that Conboy plasma dilution might have to be done repeatedly.  However, if it really resets the Horvath clock to a younger age, that would be a permanent reset (since it's embedded in the epigenome) and would not require regular treatments (except to get later additional resets).  That's why I think it's important to do the before-and-after Horvath methylation measurements.

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      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      JGC  I agree Elixir would be better, but it isnt available. I was strictly speaking of what was available right now to try to get this treatment or close to it.


      I dont think the conboys are reversing horvath with their therapy, frankly because it cant, there is nothing in their therapy, they arent giving anything, so what would be rewinding the clock? So I don't think it is permanent just like infusing young plasma from ambrosia isnt permanent and has to be readministered. They are diluting signaling molecules in the blood that tell the body to act old which is mimicking a young person blood but since the cells are still old the old signaling molecules will build back up. I think only elixir is winding back the horvath clock and then telling the body to express the pattern of young blood which should make conboy therapy unnecessary but it would still be a good idea to dilute the plasma at the same time you take elixir because who knows how long they persist and could start to rapidly re-age the newly unaged rewound cells. Katcher mentioned this.

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      • JGC
      • JGC
      • 3 mths ago
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      Fred Cloud 

      Does Conboy plasma dilution reset the Horvath clock?  That's an experimental question, and someone needs to do the experiment.  I have asked Irina Conboy by email why they didn't do Horvath clock measurements on their rats, but no replies yet.  If they have frozen blood samples left over from the experiment, they could still do those Horvath tests.

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      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      JGC Yes, ultimately a test would answer the question whether it does or doesnt.

      But what does it matter? it doesnt have to reset the clock to be therapeutic, right?

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      • JGC
      • JGC
      • 3 mths ago
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      Fred Cloud 

          In my opinion, it matters a lot.  Most of the available anti-aging therapeutics (e.g., D+Q, Fisetin, NR, etc.) fix some problems but have no effect on the epigenetic clock.  The only treatments of which I am aware that have some effect on the clock are: (1) The Yamanaka Factors (which lethally set the clock to zero), (2) The Turn Bio treatment (which won't be available for 5-10 years), (3) Steve Perry's GDF11 treatment (which he claims moves back the Horvath clock by a few years), and (4) Harold Katchner's Elixir (which has large Horvath-clock reset effects on mice and is "upstream" of GDF11).

           In the long run, we a reliable way to first clear away the senescent cells (Oisin Bio) and then reset the Horvath epigenetic clocks of all the remaining cells of the body (preferably to an age of about 25 years.)

      Like
      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      JGC Sure, ideally you want to reset the horvath back to age 25, agreed. But are you saying you won't do the conboy therapy or any therapy unless it is proven to reverse the clock even though it has shown to be therapeutic and extends life?

      Perhaps I am not following you and we are talking about two different things as you didnt say why it matters a lot?

      I say in the meantime follow the research and use what we have access to right now until we have the holy grail.

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      • JGC
      • JGC
      • 3 mths ago
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      Fred Cloud 

      It matters a lot to know if the Conboy plasma-dilution treatment resets the epigenetic clock, because it would be the most readily-accessible technique that would do that.

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      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      JGC Still not sure I am following you on this. Are you saying you it is a determining factor for you whether or not to do the therapy based on if it rewinds the clock or not rather than if it is therapeutic or not?  plasma dilution is essentially available now and is shown to be therapeutic, thats good enough for me, if it resets the clock that is a bonus and is not a deal breaker if it doesnt. Are you saying it is a deal breaker for you if it doesnt?

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      • JGC
      • JGC
      • 3 mths ago
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      Fred Cloud 

            No, what I'm saying is that there is a definite possibility that the Conboy plasma dilution, like Katcher's Elixir, resets the Horvath clock.  If it does, that's really important.  If it doesn't, it is still an interesting treatment worth considering. 

           However, I'd like to have some reports of human results from using it before jumping in myself, since Conboy's work was done on rats.  Also, although plasmapharesis is a standard and available treatment for immunological diseases like lupus, I'd like to know how much such a treatment costs and how hard it is to persuade an MD to sign you up for it as a treatment for aging.

      Like
      • Chan
      • Chan.1
      • 3 mths ago
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      JGC I want more than anything that you and Staffan shave 20 years off your life because you guys deserve it for your participation, and because it'd be a confirmation that anti-aging is reality.    Please keep at it.

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      • Chan
      • Chan.1
      • 3 mths ago
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      JGC and Staffan,

      You guys please try bitter melon.   Get fresh fruits from Asian store and juice them then leave in the fridge and drink a few sips after meal.   I believe this will help you a lot.   I believe that because I think disease fighting is a major contributor to aging.   If you can boost your innate immunity with bitter melon, your adaptive immunity has a chance to recover and you'll be younger in the long run.   I formed this opinion because I thought about rapamycin, how it suppresses innate immunity and allows the body to recover, becoming younger.    Please watch the video.

      https://www.youtube.com/watch?v=5--YRtQ7sgw

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      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
      • Reported - view

      JGC The best approach to get it is to find a doctor that is doing it and offering therapeutic pheresis rather than trying to persuade an MD to prescribe it which will most likely be a lesson in futility. Dr Cook in the bay area is on the cutting edge and will accommodate and there are others you just have to seek them out.

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      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      Chan Do you have science or studies or data or just beliefs?

      Like
      • Chan
      • Chan.1
      • 3 mths ago
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      JGC Blood sugar spikes prevent phagocytosis (a component of innate immunity) and bitter melon suppresses sugar spikes.    Preventing phagocytosis may trigger other infections and may trigger adaptive immunity (which involves manufacturing of sugar based antibodies).    This activity requires stem cells/B-cells and is "energy" intensive.

      Like
      • Chan
      • Chan.1
      • 3 mths ago
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      Fred Cloud what specific you have issue with so I can best answer you?

      Like
      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      Chan All studies showing antiaging effects of bitter melon

      Like
      • Chan
      • Chan.1
      • 3 mths ago
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      Fred Cloud this is not a specific question so I don't feel like answering you.   The logic is sugar causes activation of the immune system, which means the body is forced to fight defense/offense war against phathogens, leaving no or little energy to grow younger.    I wouldn't doubt the potency of bitter melon to suppress sugar though.   A high enough dose could cause permanent sleep, it's a very good sleeping pill because by suppressing blood sugar, the body discovers it has no energy and "shuts down" by going to sleep.

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    • Fred Cloud Do you have a link to get in touch with Dr. Cook?  I would like to contact him.

      Like
      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      Dorian Gray https://www.bioresetmedical.com/dr-matthew-cook/

       

      He did a podcast with Ben Greenfield and he talks about the "The Full Body Blood Change Reboot"

      https://bengreenfieldfitness.com/podcast/lifestyle-podcasts/cbd-thc/

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      • Jim N
      • Jim_N
      • 3 mths ago
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      JGC Companies will pay you for your plasma.  For example, this one in San Diego will pay you: https://octapharmaplasma.com/donor/plasma-donation-faq 

      However, they may take the good stuff and put in the aging stuff back into your blood, which will increase your Horvath clock. Their FAQ says, "Plasma is the liquid part of your blood that carries red blood cells, white blood cells, and platelets. It’s made mostly of water and proteins. Because it has so much protein in it, plasma is used to make life-saving medicines that treat patients who have experienced trauma, have bleeding disorders, have trouble fighting infections because of immune diseases, and more."

      I am thinking it is not the protein, red blood cells, white blood cells, and platelets that is slowing down the epigenetic clock.  It has to be other factors in the blood, specifically signalling molecules that needs to be removed.  

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      • JGC
      • JGC
      • 3 mths ago
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      Jim N 

      I would be surprised if anyone would pay me for my 85 year old blood plasma.

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      • Larry
      • Larry.1
      • 3 mths ago
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      JGC My understanding is the Conboy's don't think much of Horvath's clock but I've also heard that Horvath has agreed to test tissue samples from their experiment. 

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      • Jim N
      • Jim_N
      • 3 mths ago
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      JGC Sorry, 85 is too old.  🙂  "To donate plasma you need to be between 18 and 66 years old, weigh at least 110 pounds, and be in good health."

      Like
    • Chan

      I am happy that you appreciate the information that we share here on this forum. Parabiosis and its offspring - how to rejuvenate the human body by using blood factors is an exciting field. 

       

      The old hard way to reap some benefits from the blood and the effect our blood has on our bodies is is to do strength training sessions. When our muscles become more fit, they send out molecules to the blood and the resulting change in the composition of the blood can rejuvenate cells distant from the voluntary muscular skeletal system. Systemic signaling is the name the Conboys use for this way of influencing distant cells in the brain, heart, liver etc.

       

      Exercise is good for us and this is just another way to appreciate how it influence our lives in a positive way. Diet and exercise is the foundation for good health.

      Like
      • JGC
      • JGC
      • 3 mths ago
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      Larry 

          Yes, by email I had directly asked Irina Conboy why they hadn't measured before-and-after Horvath ages of their mice.  Here's part of her reply: "A simple answer is that we have done something better: used our proteomics clock, which demonstrated youthful resetting (evolutionary conserved between mice and humans) in an array of 300-500 proteins."  As I understand her argument, Horvath's DNA methylation measurements are indirect, because they tend to indicate the population of genes that are switched off.  The proteomic protein assay shows the population of genes that are switched on and and are actively expressing proteins.  Therefore proteomics provides a better indication of what's actually going on with the subject's epigenetic age.

           That all may be so, but Horvath's clock is much better calibrated and allows for a direct comparison with other anti-aging work (like Harold Katcher's).  She did say that her group was discussing a collaboration with Horvath.  I hope that works out.

           In any case, I think (but I'm not sure) that the methylation clock and the proteomics clock are measuring the same epigenetic state from different directions, and that if the proteomics clock is reset, then Horvath's methylation clock is probably reset as well.  This would indicate that Conboy's plasma dilution produces a permanent (rather than a transitory) change in the epigenome in the direction of youth.  That would be very good news, because of the simplicity of the Conboy procedure.

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      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      Jim N They only pay approx $50 for your plasma?

      Yet, ambrosia charges you $8,000!

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    • $8,000?  I wonder how many 13-16 year olds would like to have a $3,000 cash contribution to their college fund.  Just a wild black market imagination exercise.

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    • JGC Larry

      The results from the conboy's group are fascinating.

      https://www.aging-us.com/article/103418/text

      And I found this comment on> https://www.instagram.com/p/CBV7_X2gq9d/

      It is a very good and short summery of the results and easy to grasp so I post it here. Here it comes:

       

      "Heterochronic blood sharing therapy' is the act of taking blood from young organisms and injecting it into the vascular circuit of old organisms. This act has been shown to rejuvenate the tissues and organs of the recipients, but interestingly, not brain functions of old mice, and inversely that young mice show rapid and significant decline in cognitive functions after receiving a single exchange with old blood.

      Most of the studies on how this works focus on young plasma (and its components) as the donor liquid. However, it has not been proved that young blood is even necessary for the seen multi-tissue rejuvenation to occur.

      In today's study, researchers show something unexpected. They replaced half of old mice's plasma with a solution consisting of salt-water and albumin (5%) while preserving blood cell levels (calling it a Neutral age Blood Exchange, NBE). The goal was to inject a solution that dilutes the plasma factors in the NBE recipient while preserving normal albumin and blood cell levels.

      Young and old mice underwent a single NBE; and, as a control test, the team performed isochronic blood exchanges, meaning young-to-young and old-to-old echanges. Various tissue structures and functions where studied 6 days after the NBE.

      In doing so they showed that a single NBE is enough to see the same rejuvenative effects as in young-to-old blood echanges: muscle repair was improved, fibrosis was attenuated, myogenic proliferation was enhanced; liver adiposity and fibrosis were reduced; and hippocampal neurogenesis was increased. Remarkeably, this rejuvenation is similar to (liver) or is stronger than (muscle and brain) that seen after young-to-old blood exchange.

      This means that the positive changes seen in young-to-old blood echanges are not due to factors in the young mice's blood, but are mainly due to the action of diluting the blood of old mice. Therefore there must exist harmful factors in old blood that are responsible for some of the negative effects of aging."

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      • Jim N
      • Jim_N
      • 3 mths ago
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      Dorian Gray When I was in high school, the Red Cross pulled in their mobile truck to get as many 18 year olds as they can, claiming they are helping saving lives.  They did this for free.  

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    • Jim N  Very enlightening, Jim!  I'm checking Autotrader ads for a suitable vehicle now.

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      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      Dorian Gray Were you able to contact Dr Cook about plasmapheresis?

      Like
    • Fred Cloud Not yet.  I may wait until September to see how things unfold with virus.

      Like
  • This may be a shot in the dark, but would systemic enzymes be capable of "cleaning the blood"?  

    Like
  • I wonder if providers will pop up and start offering plasma dilution therapy based on the results of this study? Anybody can replicate this study therapy and it doesn't involve giving anything controversial. Just a plasmapheresis machine. Which leads me to my next point. How will the FDA look at this if doctors started offering it? They came down on Ambrosia for selling young plasma, but this therapy doesn't actually use other peoples plasma that they could take issue with. I see this study as a breakthrough, not just therapeutically but from a regulatory hurdle breakthrough to offer this to the masses right now.

    So will providers popup and will the fda shut them down?

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      • JGC
      • JGC
      • 3 mths ago
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      Fred Cloud 

           I think that replacing 50% of your plasma with saline + 5% albumin would certainly be controversial.  Essentially all standard plasmapharesis involves much smaller dilution fractions, so human testing ramping up to the 50% dilution level is needed to assess side effects.  But providers will undoubtedly show up, if only to do plasma dilutions with a smaller dilution fraction.

           Incidentally, on the question of whether plasma dilution "permanently" affects the epigenome and will show up as a reduction in Horvath age, Irina Conboy recently answered my email question and said that they preferred protein testing and had used a protein-assay age clock.  It indicated that their old mice did indeed have a younger epigenetic age.  This implied that the Conboy technique does reprogram the epigenome to a younger profile.  She also said that they were in negotiations with Steve Horvath to do methylation tests on their tissue samples.

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      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      JGC Very interesting John. That would be shocking if true that it did reset the epigenome as I don't see any path to how that is physically possible. I don't know much about the protein testing and I do find it strange they would essentially go out of their way to avoid the more accepted and known horvath test and use a lesser known, obscure test. Sure, the conboys may feel that their protein testing is better than methylation but perhaps they are biased because their technique moves the needle more favorably on their protein test and not the methylation test. But I look forward to seeing an apples to apples comparison using horvath methylation.

      By the way, have you had your horvath methylation measured yet?

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      • JGC
      • JGC
      • 3 mths ago
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      Fred Cloud 

           Yes, I have had my methylation age done, and it was a just a couple  of years lower than my calendar age.

           As I understand Irina C's argument, the protein assay measures which proteins are currently being expressed by genes that are switched on, while Horvath's methylation assay indicates which genes are currently being switched off or down-regulated by methylation.   She argues that what is on is a better indication of the state of the epigenome than what is off.   That may be so, but Horvath's clock apparently works and is much better calibrated than a protein assay.

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  • - if epigenetic clock reversal is proven in dilution experiment (seems probable if there is lasting effect to proteome) than there is another reason to believe in hyperfunction theory of aging

    - hyperfunction theory is based on the assumption of post-reproductive detrimental developmental algorithms. If the epigenetic age may be shifted by means on of altered inter-cellular signalling we shall all consider that neither damage nor "loss of information" are suitable to describe the aging process.

    - furthermore dilution of old blood shall show a positive effect even for normal plasma donation (without albumin compensation). Example of US regulation:Donor Weight>175lbs(80kg); max plasma collection volume=880ml; Max Plasma Loss/1 year = 83.2 Litres

    - there are no elderly donors of plasma..   (due to regulation). That is probably one reason that there are no data to support the positive effects of old blood dilutions.

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      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      stan stone plasma pheresis is big in germany, they have centers that have a bunch of machines, looks like a dialysis center. I wonder if they will be offering plasma dilution with a extra shot of young plasma and promote it as medical tourism for anti-aging.

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      • stan stone
      • stan_stone
      • 2 mths ago
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      Fred Cloud 

      We need to see a bit more research. What can be done right away is the analysis of proteome and epigenetic clock of the senior frequent plasma donors (I learned in some countries the age limits are pretty high) .

      That could be indicative of positive plasma dilution effects and bring the answer whether albumin neutral plasma dilution is important in the process.

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      • Fred Cloud
      • Fred_Cloud
      • 2 mths ago
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      stan stone So the conboy study is not enough to convince you it has therapeutic benefits?

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      • stan stone
      • stan_stone
      • 2 mths ago
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      Fred Cloud 

      I consider that to be groundbreaking study. And I believe in the following years there will be a broad spectrum of discoveries supporting hyperfunction theory.

      In order to achieve therapeutic effects, some fine-tuning may be probably necessary. Brute force approach of "removing almost everything and compensating something" may be far from optimal for elderly human. The dietary and pharmacological interventions prior to diluting procedures followed/combined with MTOR suppression may be the way to go. It may turn out that although effective in few iterations the therapy may lead to exhaustion of stem cells..  who knows... 

      Good thing is that the effects are pronounced and the research can and will be replicated in multiple "flavours" in the following years.

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      • Fred Cloud
      • Fred_Cloud
      • 2 mths ago
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      stan stone All good points. I guess you left me hanging when said "we need to see a bit more research...." Did you mean a bit more research before they would offer it as a service or before you would do the therapy and dilute your own plasma?

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      • stan stone
      • stan_stone
      • 2 mths ago
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      Fred Cloud 

      ...with "we"  I refer to enthusiastic community of fellows like me and you..  :)  

      I'd consider frequent plasma donation after replication of the study and execution of new studies with altered parameters (e.g. volume of albumin compensation).

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      • Fred Cloud
      • Fred_Cloud
      • 2 mths ago
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      stan stone Do you currently donate blood at all? That is proven to be therapeutic, heart attack risk is slashed way down and all cause mortality also cancer risk is reduced by 20%. Plus it is easier and less invasive than plasmapheresis machine. I keep my ferritin between 50-100

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      • stan stone
      • stan_stone
      • 2 mths ago
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      Fred Cloud

      No. I am considering plasma donation.

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      • Fred Cloud
      • Fred_Cloud
      • 2 mths ago
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      Larry They replace your plasma with young plasma which has to drive the price up quite a bit for this procedure. I wonder if they will offer the plasma dilution, it sure would be cheaper. It may not fit with their study interests though.

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      • Larry
      • Larry.1
      • 2 mths ago
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      Fred Cloud I heard it cost $50k which believe it or not is way less than a hospital would charge. 

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      • Fred Cloud
      • Fred_Cloud
      • 2 mths ago
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      Larry $50k !! I posted earlier about them paying plasma donors about $50

      Thats quite a markup, what is that, 100,000% ROI?

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      • Larry
      • Larry.1
      • 2 mths ago
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      Fred Cloud That's cheap for  Heterochronic Plasma Exchange. Here is a quote from a study: "Using the above data, the average short term cost for utilizing plasma exchange for MGC was $101,140 per patient compared to IVIG which accrued an average cost per patient of $78,814".

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291869/#:~:text=Using%20the%20above%20data%2C%20the,cost%20per%20patient%20of%20%2478%2C814.

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      • Fred Cloud
      • Fred_Cloud
      • 2 mths ago
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      Larry That must mean plasma is expensive to buy, maybe the plasma brokers are the ones making all the money. I know Ambrosia doctor quoted me $8,000 for a liter or two of plasma. But the game changer here is that you dont have to buy plasma you can just dilute it and get therapeutic benefits.

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