jnorm
#21
It’s been shown that intranasal admin. of extracellular vesicles could normalize behavior and prevent reduction of PFC parvalbumin (GABAergic neural marker) in phencyclidine-treated mice. GABAergic neural function is often reduced in schizophrenia, and NMDA receptor antagonists like phencyclidine are often used to model this in rodents.
Couple thoughts…
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Dr Katcher was mentioning that the brain-blood barrier might reduce the CNS bioavailability of E5, and it seems like intranasal admin. is a potential way to bypass this. It’s a little known fact that direct nose-to-brain transport can occur through the cribriform plate (this is how N. fowleri infects swimmers), and both microvesicles and exosomes are far smaller than N. fowleri trophozoites.
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The extracellular vesicles used in this study were derived from cultured human mesenchymal stem cell. It’s in a limited context, but seeing that what works for humans can work for mice, makes me more confident that works for mice will work for humans.
Mesenchymal stem cells derived extracellular vesicles improve behavioral and biochemical deficits in a phencyclidine model of schizophrenia
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Stephen McCain offers umbilical cord exosomes, these are different from MSCs…
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I’ve had them in my knee. I would love to try an infusion.
How did the knee treatment go… outcome justify the cost?
Sadly no, although I believe it has more to do with my physiology than the product. I did start a detailed thread and then felt like it may not have been all that interesting and so decided not to post it. Maybe I should. Long story short, initially it helped enormously and I was pain free for about four months. I was completely blown away, I’ve been in pain for about five years and being free of it was huge. But, the issue isn’t just my knee. It’s deferred pain from an overstretched tendon in my right ankle, which means that my patella doesn’t sit in the joint correctly. I had my knee injected because it was the thing that hurt the most. It’s an ever present incessant burn. Because I didn’t resolve the ankle issue. I’ve reinjured my knee and the pain is back. I made the mistake of treating the symptoms and not the cause.
Despite that, I’m still pretty positive about it. I think perhaps the problem was the dose and delivery. I honestly don’t believe the pain free period was a placebo effect. I think it was too small a dose in the wrong area to have a lasting effect.
I don’t regret it, despite the cost and I don’t think it was a waste of time. I’m still pretty gung-ho on exosomes. In fact, the more research I do the more I’m convinced it’s going to have a huge role to play in regenerative medicine and healthy aging.
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Tim
#28
@Babster, I’ve been on Rapa for a year and couldn’t detect any difference between the before and after. At 75, I doubted I could benefit much and was thinking of letting it go. But then I recently suffered a compressed nerve in the lumbar spine, which caused me the utmost misery for months. I could barely walk, let alone run, which is one of those things that make me feel alive. The upshot is that I was able to run yesterday, and I have to wonder if the Rapa didn’t play a role in my recovery. I’ll never know for sure of course, but I wouldn’t bet against it.
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Studies show that aging is associated with a decrease in EV production, although senescent cells and cells exposed to pro-inflammatory stimuli (age affects immune function and there is a shift towards inflammatory responses) produce higher numbers of EVs. However, there appears to be an increase in EV endocytosis, resulting in their levels not being elevated [108].
Eitan et al. examined the levels of EVs in participants divided into groups according to age (30–35; 40–55; 55–64 years) and found that EV levels decreased with age, whereas internalization of EVs by B cells increased. EVs endocytosed by monocytes increased MHC II expression, especially EVs from older donors [109]. There are specific changes in the cargo composition in aged EVs. For example, aged-cell EVs express a lower level of galectin 3 and mitochondria and their components [110,111]. Interestingly, expression of CD63 in EVs differs in the cerebrospinal fluid (CSF) and plasma with age, as shown by de Andrade et al. in a mouse model [112]. Whereas the expression increases in the CSF, it decreases in plasma. In plasma, levels of IL-1β increased with age. Geotzl et al. showed that platelets from older subjects express a higher level of alarmin HMBG1 (high mobility group box 1) [113].
[but cancer creates/overproduces its own EVs]
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Paul Tozour tried a higher dose of exosomes (though he paid like $3000 for it) and felt strong effects in terms of energy/etc
Why are they so expensive?
Stephen McCain’s are the least expensive
I tried 12.5b, and they didn’t make me feel different… It may have been worth luring me to Vegas for A4M, and maybe the negative result might still have been worth it for other reasons (testing), but…
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Exosome therapy cost $5,000
Exosome therapy is expensive. A survey I did of online prices from those selling exosome therapies yielded an average price of about $5,000.
Those selling exosome treatments are often charging thousands of dollars for something that likely costs only about $50-$100 dollars per dose to make. Talk about a markup.
It used to be that the cost of exosomes was far less than stem cell therapies, but now they aren’t so different. See my recent post on stem cell therapy cost.
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He also did plasmapheresis, a series of 6 treatments like I did (but I think he did it in Texas or Tennessee or somewhere in that general direction) - and he said it made him feel great. I did it and didn’t feel a thing. So… who knows?
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@RapAdmin Did you get the placebo or the real deal?
It turns out I got the real deal. $30,000 worth of plasmapheresis treatments (6 treatments of 3 hours each) over a 3.5 month period. And I didn’t notice any benefits. In fact I was very sure I was on the placebo arm of the trial given my results, but I was wrong. I’m hoping it at least reversed some biological aging metrics, but don’t have any visibility on that (and they won’t share individual results, just group results).
Apparently Dobri Kiprov announced some early results from his clinical trial at the A4M meeting last week, but I’ve yet to hear what he reported.
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I think that means you’re a very healthy individual.
My father started Rapamycin and didn’t notice any effects except maybe a little fatigue. But he was doing intermittent fasting before (OMAD), going to the gym, and is a vegetarian. He may have been too healthy to notice anything just like you.
I at least had some euphoric fatigue and canker sores from Rapamycin. Since then I’ve gotten healthier (stronger?) and noticeable effects from Rapamycin have become weaker.
My theory is that the healthier you are, the less you will notice things that can make you even healthier because it’s hard to move the needle when you’re that healthy.
Now we just need to find a RCT of short-lived humans to test this theory on. 
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So young plasma is a source of billions of exosomes: https://www.youngplasmastudy.com/copy-of-parkinson-s-study (and it may be cheaper than raw exosomes + contains more)
But that’s still from young adults, not neonatal, so for someone like me it would make no difference (esp b/c most Western young adults themselves are not that healthy)
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You’re way ahead of the curve, Alex. 
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“Conversely, Katcher’s intravenous infusion of exosomes (E5) has a dramatic effect on the Horvath rodent/human clock, reducing epigenetic age by half [39, 40], but thus far seems to extend lifespan less than the clock setback would imply [41].”
" Another aging clock confirmed Horvath results, GlycanAge developed by Professor Gordan Lauc also showed age reversal of around 50%.
Lauc said, “Human studies clearly demonstrated that glycans are very responsive to different interventions, but changes are usually relatively slow and not too extensive. Dramatic reduction in glycan age of rats treated with E5 is fascinating.”
Michael Snyder, Chair of the Department of Genetics and Professor of Genetics at Stanford University who did not participate in this study but sits on the Scientific Advisory Board of Yuvan Research said, “The results are stunning and have enormous potential, not just for humans, but also for animals including pets.”"
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Neo
#40
Interesting read, thx for sharing.
