What is “D+Q”?
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What is “D+Q”?
This line is just copy fill to post.
Dasatanib and Quercetin - D+Q
Also… From Irina:
Ectopic albumin in saline replenishes the albumin that is lost during TPE - discarded with the plasma. In a typical TPE, ~70% of blood is removed at once, such that blood is separated into plasma (which contains albumin as the most abundant protein) and blood cells; plasma is discarded and cells are resuspended in saline + commercial albumin and returned back to the patient.
I do not recommend doing rounds of plasma donations or frequent plasma donations as there is no evidence that health would be improved; a large acute dilution of the age-elevated proteome is the set-up that we studied in a pilot; this is accomplished by TPE. Plus, I recommend waiting for the results of the controlled clinical trials on TPE, which Dobri is conducting.
Irina Conboy, PhD
Professor of Bioengineering
Executive Committee UCB/UCSF Graduate Program
College of Engineering Research Council
A person shares their pre and post plasmapheresis blood test results:
FYI, in case anyone’s interested, I’ve attached my blood work (via LabCorp) which was taken immediately before and after each of the two TPE treatments last week.
I was not fasting either day, so blood glucose doesn’t mean much.
My liver biomarkers (ALT and AST) were scary high going in but seem to have fallen quite nicely; here’s hoping this continues as my liver gets back to normal. I’ve also gone cold turkey on alcohol – was drinking 1 glass of red wine daily until mid-September but now at zero.
Copper and zinc were both too high and both dropped substantially; I believe the TPE also included a small amount of zinc (maybe copper as well?) to even things out, along with magnesium. I will ask the clinic about this.
Just for fun, I ran the results through the Levine PhenoAge calculator. I substituted 0.4 for CRP, my last known reading from months ago, although this likely went down during the therapy. I was initially hopeful that there would be an age reduction as the post-TPE on Tuesday was 3 years lower,
Albumin went up nicely due to the albumin infused with the therapy.
I would be interested in the results 6 months or a year from then to see how the blood stabilized. Also quitting alcohol is a big game changer right there. What percentage of the benefits are from that?
Related to this thread, these Russian biohackers first tried the plasma dilution therapy two years ago, as covered in this news story (see link at bottom of this post):
The group’s scientific advisor, Alexander Fedintsev (read our interview with him) devised a protocol for plasma dilution in humans and a panel of biomarkers to watch. Then, following some logistical wizardry, the procedure was performed on two volunteers. Though not a scientific study per se, this experiment produced interesting, overall positive, results that can potentially influence and guide further research. Our interviewees think that biohacking, when done right, may become an important factor in the longevity field.
How did you choose the tests for the panel?
It would have been interesting to look at cognitive and muscular markers, but both our participants were too young: 50-60 years old. They probably do not have sarcopenia or cognitive decline yet, so there was no way for us to measure it. We chose different biomarkers, such as liver function – both of our participants had had some abnormalities in their liver biomarkers. We wanted to check kidney function because it declines with age. We checked the immune system, because as we age, the number of naïve T cells declines, and these are indispensable for fighting new infections. Immunosenescence is a hot topic in times of COVID. Hematopoietic cell aging is characterized by a shift towards myeloid progenitors. We looked at the ratio of neutrophils and lymphocytes, how it changed. Cholesterol is another important marker in the lipid profile of blood. We did a very comprehensive lipid profile that included a rare biomarker that many labs do not check for – oxidized low-density lipoproteins (Ox-LDL). I can say that this marker plummeted all the way down to its normal level in one participant that had it elevated prior to the procedure. We also checked for various hormones, including insulin-like growth factor (IGF), that are related to aging and lifespan, and many other markers, including biochemical ones, such as urea and uric acid, along with oxidative stress markers, such as lipid peroxidation products and glutathione. Contrary to epigenetic clocks, these markers can be clinically interpreted.
Do you plan to publish the results, maybe as a case study?
We have all the data published as a Google spreadsheet on our website so that researchers can see it. We do not plan to publish an article. First, I am convinced that soon we will have full-scale clinical trials of this method, maybe by the Conboys, and there is something in the works here in Russia as well. I do not know how valuable our data is, considering our sample size was just two people. We just wanted to see whether it was possible to arrange such an intervention in humans using the means we had at our disposal, and whether it would do any good. Now we know it actually did some good, in terms of the number of naïve T-cells, levels of oxidized LDL. The drop in Ox-LDL levels was probably due not simply to dilution but to some deeper processes, because in one participant, these levels declined, while in the other they went up from an originally low level. So, in both participants, LDL levels normalized and stayed normal for at least two weeks. Liver markers improved by a lot, and the myelocyte/lymphocyte ratio improved. There were some controversial results, such as one participant having insulin levels decline four-fold but not the other one.
The Russian Biohacker Website (use the google chrome web browser for automatic translation of the website): BIOHACKERS FOR LONGEVITY - Scientific Expert Group RLE
RLE Group is a biotech startup with a mission to develop bioengineering solutions for healthy life extension. Founded by a group of scientists and biohackers known for their experiment to translate therapeutic plasma exchange on human beings.
Not so long ago we wrote about a new promising method of rejuvenation: plasma donation with the replenishment of an important transport protein - albumin. The essence of the method is to dilute the plasma, reducing the concentration of harmful substances in it. Plasma dilution or dilution still sounds long enough, so from now on, we will simply call it plasmapheresis, although this is not entirely correct. In the article, I highlighted the benefits of this method in detail, and our team decided to try it out for themselves. Interestingly, as soon as we did the first procedure, another article came out where the authors emphasized that plasmapheresis reduced neuroinflammation and improved cognitive function. But can this intervention improve people’s health?
As you can see, most of the markers decreased in both biohackers, many markers returned to normal, although initially they were much beyond the reference values. Let’s look at the markers by groups:
- Liver markers showed excellent positive dynamics in both participants . The AST values reached the norm, and the ALT values did not reach the norm quite a bit, but it is possible that liver recovery is a slightly longer process and 3 days is not enough.
- Hormones . IGF-1 did not change significantly in any of the participants. Interestingly, insulin decreased in one experimenter by almost 4 times! Unfortunately, in the second it increased (albeit within the normal range), which does not allow us to think about the presence of a reliable effect.
- Kidney function remained apparently unchanged. Creatinine decreased slightly in both experimenters, and cystatin C showed multidirectional dynamics.
- A downward trend was demonstrated by such markers as uric acid and urea .
- The situation with the lipid profile is extremely interesting . One of the participants in the experiment had an excess of total cholesterol, LDL, HDL and, most importantly, oxidized LDL , which damages the vascular endothelium and promotes atherosclerosis through a number of other mechanisms. So, they all returned to normal, and oxidized LDL decreased by almost half ! Of course, one can argue that there was simply a 2-fold dilution of the plasma, so oxidized LDL decreased by 2 times, but the nuance is that in the second participant in the experiment, the values of cholesterol and individual fractions increased (remaining within the normal range)! So the simple hypothesis of lowering cholesterol due to dilution is less plausible and there is hope that there is not a one-sided decrease, but optimization . cholesterol levels (high falls, low rises). We will test this hypothesis later.
- One of the key features of aging is chronic systemic inflammation . Both of our brave experimenters had a slightly elevated C-reactive protein. In both, it decreased after the intervention, while this reduced level persisted for at least one more week in one of the biohackers (the other has not retested yet).
- And another very interesting change is an increase in the number of naive lymphocytes (by 37%)! Naïve lymphocytes are the most important marker of the aging of the immune system and their number steadily decreases as the body ages, so their increase is undoubtedly a positive sign. Unfortunately, due to technical reasons, we were only able to perform this analysis on one person. However, both experimenters had a significant decrease in the ratio of neutrophils to lymphocytes, which is another marker of the aging of the immune system. Moreover, for both, this marker either remained at a low level, or continued to decline 10 days after the last procedure. So with caution, perhaps, we can talk about some potential beneficial effect onimmune system .
- Albumin did not change in both participants, which means that we correctly calculated the dose and the intervention turned out as planned.
Thus, our data indicate the potential for therapeutic dilution of plasma. Of course, this pilot mini-study has a lot of limitations: an ultra-small sample size, relatively young and relatively healthy participants, an incomplete protocol, not all biomarkers were retaken, it is not clear how long the result lasts, if there is an effect, etc. We will definitely take all this into account. But if repeated experiments show that there is an effect and it is long-term, then we get almost the first intervention that has a systemic positive effect on the body for a long time without the need for frequent repetition. And this is exactly what biohacking is in our understanding. Not drinking unproven useless (and even potentially harmful) dietary supplements, but such serious medical procedures. Of course, there is also the question of causality - will positive changes in these markers prolong life? It is impossible to give an exact answer to this, but based on an understanding of human physiology and the biology of aging, the answer is rather yes.
Most likely, something like this has been done for a long time, but it’s nice to know that we were the first to do therapeutic dilution of plasma with the addition of albumin, measure markers and openly talk about it. We express our deep gratitude to Andrey Isaev, the head of the network of DNA laboratories , where we handed over the biomarker panel, as well as to all the doctors who did their job in a highly professional manner. Register on our website to receive regular updates and access to restricted materials (for example, a panel of biomarkers and a description of the protocol for this study) - there is a lot of interesting things ahead of us, because our group has several more promising projects in the works.
I’m just poking around the Russian website of the RLE Group (Radical Life Extension Group). They seem to be a very qualified group of people and have Leonid Peshkin of Harvard as an advisor. We covered Leonid Peshkin previously in this story: A Blueprint For Radically Open, Citizen Science Approach To Aging Research
A video interview / presentation with Alexander Fedintsev, a founder of the Russian biohacking group is below (The Foresight Insitute link below also has a full transcript/slide presentation if you prefer to not watch video and want to skim the presentation):
The Russian group is working on a gene therapy approach also (similar to what George Church and Rejuvenate Bio are doing it seems):
Studies have shown that such long-livers had a much higher activity of certain genes: FOXO, KLOTHO, SIRT, FGF, AMPK, etc.
Higher activity of these genes protects against senile dementia, sarcopenia (age-related muscle wasting), various oncological diseases, atherosclerosis, kidney failure, diabetes and other age-related diseases that eventually lead to death. Moreover, animals with artificially activated “longevity genes” lived 30-40% longer than their wild-type counterparts. The role of these genes in aging has been proven by a plethora of studies, but activation of these longevity genes is far from the routine clinical practice.
But what about those who are not naturally gifted with such active longevity genes? The solution is obvious: inject additional copies of these genes to the body for the constant production of “youth hormones”.
Methods of gene delivery into a cell (vector delivery) is already widely tested: almost all COVID-19 vaccines, such as Pfizer, Moderna, AstraZeneca, etc., are based on this technology, and have proven its effectiveness and safety literally on billions of patients worldwide. These vaccines carry the genes for specific COVID-19 virus proteins that trigger the body’s immune response.
The problem is that existing viral vectors aren’t safe because they can integrate in the genome and cause potentially carcinogenic mutations. In addition, viral vectors are costly and difficult to manufacture. mRNA vectors are much safer but they are extremely unstable and short-lived.
We, the Radical Life Extension Group (RLE Group), started developing our own vector three years ago and are working to deliver the genes needed for health and longevity. We decided to create a non-viral vector that is safer, easier and cheaper to produce and this is a crucial step towards a universal platform for longevity genes delivery.
We are testing a genetic vector, carrying the famous longevity gene Klotho, and its new cell delivery system based on silicon nanoparticles, the surface of which was laser-treated to increase their penetration efficiency. We are now testing it on cell cultures, and by early 2023 plan to proceed to preclinical trials on model animals - rats and guinea pigs. around the summer of 2023, we plan to make two vectors for pets - cats and dogs, and by the end of 2023 - a version for humans and become the first testers of this technology ourselves.
Related to this thread:
Dobri Kiprov at a recent conference, presenting on plasmaphoresis for aging (Therapeutic Plasma Exchange or TPE).
He’s starting a new company called Lyfspn and we have people on our forums here who are participating in the clinical trial and getting treated using TPE. Dobri Kiprov’s office (right now) is just over the Golden Gate Bridge (San Francisco) in Mill Valley.
More good news on Plasma Therapy (Therapeutic Plasma Exchange TPE, or Plasmapheresis) or similar therapies. But I think this was the Dr. Katcher formulation with relatively minor improvements in lifespan.
YOUNG PLASMA REJUVENATES BLOOD DNA METHYLATION PROFILE, PROLONGS MEAN LIFESPAN AND IMPROVES HEALTH IN OLD RATS
Priscila Chiavellini, Martina Canatelli-Mallat, Marianne Lehmann, Joseph A Zoller, Juozas Gordevicius, Maria Delfina Gallardo, Diana Camila PAsquini, 'Claudia Beatriz Herenu, Gustavo Ramon Morel, Steve 'Horvath, and Rodolfo G Goya
bioRxiv. posted 2 December 2022, 10.1101/2022.12.01.518747
There is converging evidence that young blood conveys cells, vesicles and molecules able to revitalize function and restore organ integrity in old individuals. Here, we assessed the effects of young rat plasma on the lifespan, epigenetic age and healthspan of old female rats. Beginning at 25.3 months of age, a group of 9 rats (group T) was i.p injected with plasma from young rats (2 months) until their natural death. A group of control rats of the same age, received no treatment. Blood samples were collected every other week. Survival curves showed that from age 26 to 30 months, none of the T animals died, whereas the survival curve of C rats began to decline at age 26 months. The external appearance of the T rats was healthier than that of the C counterparts. Blood DNA methylation (DNAm) was assessed using the HorvathMammalMethylChip320. Blood DNAm age versus chronological age showed that DNAm age in young animals increased faster than chronological age then slowed down progressively, entering a plateau after 27 months. Immediately after the start of the treatment, the DNAm age (i.e., epigenetic age) of the treated rats fell below the DNAm age of controls and remained consistently lower until the end of their lives. Assessment of each experimental group showed that the blood DNA methylation levels of 1638 CpGs were different between treated and control blood samples (q-value<0.05). Of these, 1007 CpGs exhibited increased methylation, with age while 631 CpGs showed decreased methylation levels. When rats were grouped according to the similarities in their differential blood DNA methylation profile, samples from the treated and control rats clustered in separate groups. Analysis of promoter differential methylation in genes involved in systemic regulatory activities revealed specific GO term enrichment related to the insulin-like factors (IGFs) pathways as well as to cytokines and chemokines associated with immune and homeostatic functions. We conclude that young plasma therapy may constitute a natural noninvasive intervention for epigenetic rejuvenation and health enhancement, readily translatable to the clinic.
Heard in passing for years - conspiracy stuff that royalty (guess who), the oligarchy, politicians, Hollywood stars and wealthy CEO’s were doing this with kid blood to stay young.
Damn - need to get a transfusion of young O+ blood from some healthy college kid.
I am next in line - lol.
Kid poop is magic too, dig in!
Probably not completely conspiracy stuff… but the issue is it hasn’t been well proven from a research standpoint/ efficacy standpoint yet.
Yep - I raised a son and daughter and a granddaughter… poop is not magic! LOL.
The thing about blood is clearly something that exists in the plasma of older people to a greater extent and not in the cells. Hence plasma dilution has some beneficial effect.
It happens to be that I think the something is IL-10 which is part of SASP. The reason people don’t focus on IL-10 is that strictly it is considered anti-inflammatory, but in fact it is its actions on NF kappa B that causes senescence (through the Janus Kinase - which is why JAK inhibitors also have some anti-aging effects).
Did they make Thiel look like Dracula on purpose for that picture?
Curious how that magic poop is delivered. Colonics? Colonoscopy?
I did read an article on this quite a long time ago and that’s what they said. My thought was that we have just been wasting this resource all these years. 5 kids, 10 grandkids and that’s a lot of poop. It’s gross so I didn’t do much more thinking on it.
Then Agetron started talking about using plasma from young men and I just said that to yank his chain. I don’t know whether it costs a college kid some health to donate plasma, but to me at some point it’s like drinking unicorn blood in Harry Potter and it’s probably a slippery slope. With poop the risk is all on the recipient, so I really can’t object.
Gotta add that the yogurt actually tastes good and contains all kinds of good nutrients so that is going to be my best first try.
My thoughts are that if you were to do this…and that’s a huge “if” it probably would work better with your own genetic offspring …my son’s drained my energy, finances and mental health for 32 years it’s payback time.
I want payback in blood…literally…hahaha.
He’s on rapamycin 2mg a week… no GFJ.
Payment in blood is no longer a figure of speech!!!