SENS Research Foundation on Recent Plasma Dilution Research

The SENS Research Foundation scientific staff here discuss the recent results demonstrating benefits to an aged metabolism resulting from dilution of blood plasma. Plasma dilution is a comparatively simple process, straightforward enough that self-experimenters with the support of physicians recently replicated the animal study protocol in a few human volunteers. Dilution of blood plasma also dilutes harmful signal molecules present in an aged body, such as those generated by an increased burden of lingering senescent cells. This reduces chronic inflammation and improves tissue function in older individuals.

When researchers surgically conjoin the circulatory systems of a young and an old animal, something remarkable happens: the older animal recovers some features of youth, while the young animal becomes functionally older. This phenomenon is called heterochronic parabiosis. A possible player in the pro-aging/rejuvenating effects of parabiosis that has been largely ignored until recently is the potential role of metabolic toxins and wastes. In addition to the cellular and molecular damage of aging that accumulates in our bodies over time, the body's normal metabolic processes also produce an enormous amount of more transient metabolic waste every day. In youth, much of what could go to waste is instead reprocessed and reused, and the rest is detoxified and excreted.

As we age, however, the organs responsible for detoxifying and eliminating these wastes - the kidneys, the liver, and to a lesser extent the lungs - age along with the rest of us, and their ability to remove these wastes progressively degrades. As a result, waste levels in blood circulation rise with age. These metabolic toxins are definitely bad for us - just ask a patient waiting for a liver transplant or on haemodialysis. Consistent with this, a biomarker called cystatin C, the most reliable marker of loss of kidney function, is a powerful predictor of broader age-related decline.

At the urging of SENS Research Foundation CSO Aubrey de Grey, and with SRF funding, pioneering parabiotic researchers Michael and Irina Conboy conducted a study to tease out the role of access to a young animal's organs in the parabiosis effect in 2015. Researchers built a machine capable of exchanging volumes of blood at will, replacing them with equal volumes of blood (or plasma, or other substitute fluid). They found that the benefits of directly trading old blood for young were dramatically less impressive than the effects of full-on parabiosis complete with the filtering and detoxification services provided by young liver and kidney function.

On the other hand, receipt of young blood did enhance the repair of old animals' muscles after injury, although the effects were less impressive than what's seen in parabiosis - and in this case, there was no inhibitory effect on the muscles of young animals exposed to old blood. Similarly, the ability of an old animal's injured liver to regenerate was enhanced by young blood, and existing age-related fibrosis improved. These experiments show that these health effects are not mediated primarily by removal of metabolic wastes, though certainly they could still be mediated by dilution effects rather than true active-factor transfers.

By this point, a direct test of the dilution hypothesis would seem to be in order - and recently the Conboys ran one. With the blood-replacement machine up and running, they replaced half the blood of old mice - not with young blood, but with saline solution, plus an amount of the albumin protein family equivalent to that in blood, to avoid losing albumin's important non-signaling functions in transporting different substances around the body. Like young blood itself, this "neutral blood exchange" (NBE) substitute (as they called it) would lack all of the pro-aging factors that an old mouse's blood would contain (as well as the metabolic sludge its aging organs would have failed to remove) - but, importantly, would not contain any of the pro-youth molecules that some think are responsible for the effects of heterochronic parabiosis.

Remarkably, a single NBE treatment rejuvenated muscle repair capacity of old mice to equivalent levels of quite young control animals, including major improvements in the number of muscle stem cells engaged to regenerate the damaged muscle, the area of muscle where such cells were active, and in the level of fibrosis left behind. NBE also significantly improved liver health in old animals, partially reversing their fibrosis and reducing the pathological fat deposits in the organ.



So.. Would donating plasma be a way to get some of the beneficial effects of " dilution of blood plasma" as well?

Posted by: august33 at January 19th, 2021 9:04 PM

@august33. This is an excellent question and I am surprised no one has answered this yet.
Before the Internet (or in its early days) I read a short article that said someone had done a study and discovered that people who donate blood tend to live longer. So now, maybe we know the reason why! If you Google this question you will see newer articles on this. Here is just one:

Posted by: Dean at February 21st, 2021 12:07 PM

@august33 & @Dean I've been a blood donor over the years and after learning of the Conboy dilution experiment noticed that during my last whole blood donation my local blood bank was also asking for plasma donations. Big differences between plasma and whole blood donations. Plasma donation will removed about 20% of plasma in one go vs about 8% with whole blood donation, and can be done every 4 weeks vs every 8 weeks for whole blood. I plan to make 3 plasma donations in quick succession which will take 8 weeks and do routine blood work along the way. Some expected changes may not be measurable, like reduction in liver and muscle fibrosis. I'm 66 yo, so would expect some benefit.

Posted by: Peter at February 24th, 2021 12:57 PM

I was having the same thoughts about donating plasma to get rid of "junk". So Peter, will you post any findings from your testing? Also, I thought plasma donations can be done every few days (twice a week). Any research on what to be doing after donating plasma, like eating more protein or supplements? Lastly, I think plasma donation has an age limit of about 69 or even younger. So this might not be an ongoing strategy when you reach 70 and beyond.

Posted by: Vince at May 18th, 2021 10:07 AM

in follow-up to Vince, yes, I have found that plasma only donation centers do generally have an age limit in late 60s, and they do allow two donations a week of up to 800 mls eaach donation depening on body mass, so that you can quickly cycle through your old plasma in less than two weeks. I am 67yo and would need to drive two hours to make use of this, which I intend to do soon when I resume donations. The age limit does not apply at the local blood bank donation centers, although allowed donation frequencies are much less. This last summer I donated double platelets every two weeks as these were in short supply for cancer patients. Plasma goes along with platelets so on average I loose about 450 mls of plasma every two weeks. This may not be enough at one time to make a change in gene expression that Conboy observed, but she did say that some of the gene exression data was collected up to a month after NBE, so I'm guessing that loosing approx. 1700 mls over 6 weeks should have a positive effect. Albumin is not replaced in thse donations, but doing CBC I see that my albumin levels were maintaned.

Posted by: Peter Ezzell at December 20th, 2021 4:07 AM

@Peter Did you do the rapid succession plasma donations? Did you measure any benefit? Thank you!

Posted by: Matt at January 5th, 2022 7:31 PM

I recently informally tested plasma donations. I did 6 donations of 800mL of plasma once a week over 7 weeks with one skipped week (the new technician had trouble getting the needle in that week). The skipped week was at the beginning. I did a standard blood test (complete blood count and CRP) before and after the test. The result was that everything was within the variation I normally see in blood tests, with no clear significant improvement.

Of course, there is a long list of caveats. The first is that my blood labs are already quite good for my age and both 3.0 and Levine's Plasma Phenoage give me a "biological" age of 32, whereas I am 47. So, it might be that my plasma is already as good as could be achieved with plasma donation. But, also, this was just one person, I didn't have absolute control of my diet and life style, though I tried to keep it fairly close to the same, I may not have tested the right biological parameters,...

And, there is the possibility I needed Albumin replacement or a larger volume or a different frequency, and so on. Nevertheless, it didn't hurt anything and was worth a go. Fortunately, there is an ongoing clinical trial randomly assigning plasma donors to receive saline with albumin or without it.

Also, there was recently a paper on bioRxiv about plasma donations without albumin that showed that there was an improvement to some of the plasma parameters discussed in the Conboy paper. The trial was small.

Posted by: Neil at January 6th, 2022 1:44 PM
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