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?
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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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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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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."
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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.
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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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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." -
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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Dorian Gray Were you able to contact Dr Cook about plasmapheresis?
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Fred Cloud Not yet. I may wait until September to see how things unfold with virus.
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This may be a shot in the dark, but would systemic enzymes be capable of "cleaning the blood"?
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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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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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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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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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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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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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stan stone So the conboy study is not enough to convince you it has therapeutic benefits?
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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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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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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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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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