Today's news from the self-experimentation community notes a more adventurous effort, in which a few volunteers underwent blood plasma dilution followed by assessments of function. Plasma dilution, or neutral blood exchange, involves extracting blood, replacing the plasma fraction of that blood with saline and albumin, then reintroducing the new mix. The effect is a dilution of the circulating plasma and all that it contains. For most people this procedure is past the outer limits of practicality as a self-experiment. It requires a good amount of scientific or medical knowledge, familiarity with the latest research on the topic, and cooperative physicians.
Plasma dilution as a treatment to favorably adjust the age-damaged operation of metabolism is one of the more interesting outcomes of heterochronic parabiosis research. In a heterochronic parabiosis study, old and young mice have their circulatory systems linked. The old mice show signs of reversed aging, while the young mice show signs of accelerated aging. Is this because of factors in young blood that improve the function of old tissues, or is it because old blood is packed with damaging factors that impair tissue function?
It may be both, but the most compelling evidence points to old blood being full of actively harmful molecules, such as debris from damaged cells, the inflammatory signaling of senescent cells, and so forth. Diluting these signals restores a better operation of tissue throughout the body - at least in mice. Formal human trials lie somewhere in the years ahead, but the volunteers noted here are to be commended for responsibly stepping up to try the procedure and publish their data. It would be a better world were more of the self-experimentation community as competent in their efforts.
How did your group first get interested in the idea of plasma dilution? I understand that Irina Conboy's work had a certain influence?
Not just influence. It played a central role. The Conboys' study was published in May. It showed that simple plasma dilution can recapitulate most of the benefits of parabiosis. The original parabiosis results hinted on the existence of certain systemic factors of aging and at the possibility of its reversal. This recent study made the procedure easier and eliminated ethical controversies. The procedure is almost similar to donating blood plasma. This simple procedure yielded some interesting results: it triggered muscle regeneration in mice, liver regeneration in older animals, and improved neurogenesis. Recently, in late November, I think, another study was published that showed some real cognitive improvement following this procedure. So, now we have some serious proof that blood contains signaling molecules that harm the organism, but there is no data on whether this procedure actually prolongs lifespan. I think there is a reason for it. It is highly unlikely that this procedure results in any meaningful life extension. I think most of the effect is on healthspan rather than on lifespan. It is still good news, since we currently have very few ways to extend healthspan.
Why did you decide to participate in this small-scale experiment on humans?
Our team has existed for some time now. It is a small community of biohackers. It seemed like a great way to quickly test this intervention, get some results fast, and tell people about it.
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. 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 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.