Removing Harmful Factors in Old Blood Has Age Reversing Effect

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Researchers have found that age-reversing effects can be achieved by simply diluting the blood plasma of old mice — no young blood needed.

Above – Older mice grew significantly more new muscle fibers, shown as pink “donut” shapes, after undergoing a procedure that effectively diluted the proteins in their blood plasma (bottom) than they did before they underwent the procedure (top). (Image courtesy Irina Conboy)

Replacing half of the blood plasma of old mice with a mixture of saline and albumin — where the albumin simply replaces protein that was lost when the original blood plasma was removed — has the same or stronger rejuvenation effects on the brain, liver and muscle than pairing with young mice or young blood exchange. Performing the same procedure on young mice had no detrimental effects on their health.

This discovery shifts the dominant model of rejuvenation away from young blood and toward the benefits of removing age-elevated, and potentially harmful, factors in old blood.

Regularly cleaning our blood could improve health, much like oil changes help cars.

Therapeutic plasma exchange in humans lasts about two to three hours and comes with no or mild side effects, said Kiprov, who uses the procedure in his clinical practice. The research team is about to conduct clinical trials to better understand how therapeutic blood exchange might best be applied to treating human ailments of aging.

Aging Journal – Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin

Abstract
Heterochronic blood sharing rejuvenates old tissues, and most of the studies on how this works focus on young plasma, its fractions, and a few youthful systemic candidates. However, it was not formally established that young blood is necessary for this multi-tissue rejuvenation. Here, using our recently developed small animal blood exchange process, we replaced half of the plasma in mice with saline containing 5% albumin (terming it a “neutral” age blood exchange, NBE) thus diluting the plasma factors and replenishing the albumin that would be diminished if only saline was used. Our data demonstrate that a single NBE suffices to meet or exceed the rejuvenative effects of enhancing muscle repair, reducing liver adiposity and fibrosis, and increasing hippocampal neurogenesis in old mice, all the key outcomes seen after blood heterochronicity. Comparative proteomic analysis on serum from NBE, and from a similar human clinical procedure of therapeutic plasma exchange (TPE), revealed a molecular re-setting of the systemic signaling milieu, interestingly, elevating the levels of some proteins, which broadly coordinate tissue maintenance and repair and promote immune responses. Moreover, a single TPE yielded functional blood rejuvenation, abrogating the typical old serum inhibition of progenitor cell proliferation. Ectopically added albumin does not seem to be the sole determinant of such rejuvenation, and levels of albumin do not decrease with age nor are increased by NBE/TPE. A model of action (supported by a large body of published data) is that significant dilution of autoregulatory proteins that crosstalk to multiple signaling pathways (with their own feedback loops) would, through changes in gene expression, have long-lasting molecular and functional effects that are consistent with our observations. This work improves our understanding of the systemic paradigms of multi-tissue rejuvenation and suggest a novel and immediate use of the FDA approved TPE for improving the health and resilience of older people.

71 thoughts on “Removing Harmful Factors in Old Blood Has Age Reversing Effect”

  3. Which is my point.
    Insulin is the same way. It’s fine when it’s either in the blood or in the cells. But once it starts getting in interstitium, you start having problems. Look up insuline-induced amyloid deposits, which is seen in people that inject insulin in the same area consistently.

  4. Mice are terrible as a model for humans unless you’re pharma looking to fulfil regulatory requirements on the cheap. This is not going to extend your life.

  5. But your investments would have compounded super-fast! Put in $100, go away and come back to collect $10000.

  6. Quick, somebody inform the vampires! I’m sure there’ll still be some older, more conservative holdouts, – “We can’t move away from draining virgins, it’s tradition!”. The younger, more progressive ones might be down for it, though.

  7. Travelling at relativistic speed will cause you to age more slowly as compared to your twin on Earth, but you won’t get to live any more seconds from your own perspective, so it’s generally a terrible idea: your friends who stayed on Earth get old and die while you were only out for a bit.

  8. Probably easier to genetically modify Saccharomyces cerevisiae to generate human blood albumin than birds, which might cause problems in foetal development assuming they might be as allergic to our albumin as we to theirs. And Berkeley, I think, already managed to have S. cerevisiae produce THC and cannabidiol, so albumin would be a walk in the park, I imagine.

  9. Ironically, they were right the whole time- blood products CAN be dangerous. It used to be SOP for surgeons to top off a patient with a couple units after surgery.
    now that is unheard of. You need certain criteria to be met before blood products are given.

  10. It’s fine when it stays in the blood stream. Problem is when it starts leaking out, supposedly. (edit: but that has nothing to do with this blood dilution procedure)

  11. Senescent cells are known to release toxins into the bloodstream, causing many of the effects attributed to old age. I cannot help wondering if this is a treatment for a cause rooted in senescent cells, and if the drugs/treatments for removing senescent cells will, if proven effective, make this treatment obsolete.

  12. which is why you can have the tingling from hypocalcemia. So we check for ionized calcium before most apheresis procedures and sometimes give calcium prophylactically.

  13. What Brett said is true but the most common allergic response is just to cytokines present in blood products [IF FFP is given] triggering an immuno-response in the recipient. The reactions are usually very mild but if anaphylaxis occurs then that can be deadly.
    edit:
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711211/#:~:text=Allergic%20reactions%20to%20apheresis%20platelet%20products&text=Urticaria%20or%20pruritus%20was%20reported,No%20patient%20had%20anaphylaxis.

    This provides a brief breakdown of alergic reactions to apheresis platelets[ “apheresis” how they are collected, not administered in this context]. FFP is mostly just plasma that is given for the clotting factors [like fibrinogen, Factors 1-13, etc], but the reactions can be similar.
    Regardless, if there is a transfusion reaction of *any* kind [which can be as simple as an increased heart rate or temperature] then the infusion of blood products is halted immediately, as there is a dose-related response.

  14. That makes absolutely no sense. Albumin is the most common protein component in plasma. It’s vital for maintaining oncotic pressure and keeping fluids from third spacing. That entire statement is positively baffling.

  15. Agreed. People are getting excited about maybe rolling this out large scale, but I bet before we get there we’ll have a target or two, and we’ll be screening drugs to hit them somehow. Down regulate their production? Add an enzyme that breaks them down? Something that assists in whatever regular excretion pathway they run through? Or just something that binds them and blocks whatever toxic effect they have? Hopefully it’s just one or two easy targets. Otherwise it really might be better to just build out the bloodletting clinics.

  16. That was my gig in college. Did it twice a week, covered the food budget. Too bad it doesn’t improve the health of young people. There were some middle aged people in there. I wonder if it was giving them a boost.

  17. Plasma donation is big business, indigents can make up to a few hundred a month.
    No known accidental immortals resulted from this old trade, maybe the replacement mixture plays an important part.

  18. The next step, I assume, is characterizing exactly what is being diluted. If it’s something simple, you could probably filter it from blood somehow. Hopefully it’s not about 200 different toxins in low concentrations.

  20. Same class of protein, but that’s because the definition of “albumin” is very broad: Any water soluble protein that can be coagulated with heat is called an “albumin”.

    Egg albumin would cause an allergic reaction if injected into your bloodstream. Just wouldn’t work. Maybe you could genetically engineer chickens to produce human blood albumin. Maybe.

  21. That’s how I paid for beer and pizza in college all those years ago. The plasma center was next to a liquor store, very convenient

  22. Sure. Diluting and injecting antibodies now. Vaccine then to prevent the regular transfusions and injections.

  23. Is albumin replacement just to enable larger replacement volume? It seems like they are saying that dilution of certain protein concentrations is critical.

  24. I am not sure donation alone will do the trick, since the concentration of offending proteins might not be affected.

  26. How is this done, on a practical level?

    Removing half the blood plasma presumably means that you have to remove half the blood for starters. I can’t imagine that would be healthy, so a treatment would have to be performed by taking a bit of blood and “cleaning it”, putting it back and repeating the process. 

    Only thing is that as you continue the process, you will be “cleaning” an ever larger fraction of already “cleaned” blood. 

    Also, you want the red blood cells and all the rest back in the blood. So does this mean that a nurse has to centrifuge the blood and “suck up” the part that goes back into the blood stream and mix it with albumin? Seems like a messy process that could allow for blood contamination and infection.. Which is OK if you dealing with mice, but not with men..

  27. The most important aspect of this development is how it can be used to improve the plots of future movies. Now, imagine the villain injecting the hero with super old blood plasma, making him weak and old; CG effects with the face wrinkling up in minutes. The hero has to fight to get the antidote, i.e. young blood plasma.. In the end the hero retakes his young plasma and drains the villain who in turn turn into a emaciated skeleton.. Good stuff.

  28. You are pushing the treatment into the future. Diluting blood plasma can be done now, but creating antibodies may or may not work and it needs R&D before it would work.

  29. I’m no immunologist, however it would seem easier to just develop and inject the catalytic antibodies instead of relying on an aged immune system.

  30. The problem right now is that available port systems are prone to infection and clogging. Also it takes a skilled individual 45 minutes at least to install it. I hope a reliable interface is developed. It would be revolutionary.

  32. Plasma donors get paid in some places. Of course, that would change if everyone started donating.

  33. How about an RNA vaccine to create antibodies for the bad proteins? That should keep us young without the transfusions.

  34. Well, the article also says “However, the body of published work consistently demonstrates that albumin is a negative factor for brain health. With respect to reaching neural cells in vivo, Blood Brain Barrier becomes leaky with age [31, 32] and serum albumin crosses it and is found in cerebro-spinal-fluid of older individuals in a positive correlation with age and with certain types of dementias [33].
    Moreover, in direct test, infusions of albumin into the brain were
    deleterious: causing neuro-inflammation, excessive TGF-beta1 and
    neuronal dysfunctions [34].”

  38. I did these alot as a pathology resident. They are fairly safe and effective at treating whatever condition[ though these are stratified as far as how effective they are]. Usually it is to remove a component like a circulating antibody [like in myaesthenia gravis] or a leukoreduction in the case of an acute leukemia[ which *can* be an emergent situation].
    As long as the fibrinogen is not at a critical value then you can replace with albumin instead of fresh frozen plasma. A CBC is done before each procedure to check this level.
    The most common side effect is tingling of the lips from hypocalcemia since calcium can get basically chelated off. Usually calcium citrate is given as supplement. A reaction, usually allergic, can also develop. Anaphalaxis can also occur.

  39. It probably won’t at all. It’s also genetically related to a protein that is recessive and results in minimization of the hair follicle.

  40. These were the folks that did the original joined mice study aka the vampire mice study. The original study did prompt a lot of research that discovered the lack of NAD+ in old cells/blood, and young mouse blood did have free floating NAD+/NR/NMN so that did provide replacement benefits. This study just proved you could get most of the benefit without needing to source young blood.

    Now, as pointed out, there are some up-regulation of proteins due to the plasma replacement operation that needs to be looked at more, but it doesn’t change the fact that old animals lack NAD+ (or more accurately, they poorly recycle NAD+), so adding that to the saline/albumin mix is an easy win. What else should be mixed in on a standard basis will be interesting.

  41. This. If you look at the break down of how apheresis is done, you are centrifuging the blood on basically a conical device, which will sort the blood by density. You can fine tune what you are taking off. Say you are doing leukoreduction in a leukemic patient, you can focus more on the lymphoid population and return the other cellular components.
    As I said above, as long as your fibrinogen isn’t at a critical level and you aren’t at risk of hemorrhaging doing a hypocoagulable state, you can replace with albumin instead of FFP. A CBC is done before each plasma exchange if it is intended to replace with albumin.
    I did them a lot on call.

  42. No. Apheresis does remove cellular components but the main constituent are neutrophils and some lymphocytes, as far as the leukocytes.
    You have a large reservoir of them in your bone marrow , thymus and lymphoreticular system.

  43. More or less. I have done clinical service work on apheresis procedures and that is what it amounts to. As long as the fibrinogen is not at a critical value, then you can replace the blood volume with albumin instead of plasma products [usually ffp]. It’s fairly safe and effective.

  44. Yes, I read about this elsewhere, and it really hints at a way to create the effect of young blood without draining children.

  45. The data is probably all confounded because blood is typically only donated by young, healthy people. And usually only the ones who are feeling up to it at the time.
    So you’ve removed from your data pool everyone that isn’t already young and healthy. Very difficult to notice that the remaining people are particularly young and healthy.

  47. I very much doubt they are using your donated plasma to top up some 20-y.o. who is otherwise healthy.
    It’s going to someone who needs plasma because of blood loss, burns or disease. They are much better off with old plasma than a litre of coconut juice, which is the next alternative.

  48. Depends on the residence time of the toxins; If it’s quite long, regular plasma donations would eventually get you there. But they accomplished this by replacing half the blood volume, and plasma donation is a LOT less of your blood volume. OTOH, you can legally do it quite frequently, and each donation is 8% or so of your blood volume, so you should get there in about a month unless the toxins are replenished really quickly.

    Oh, and plasma donation isn’t free. They pay you.

  49. from the abstract
    …….”Comparative proteomic analysis on serum from NBE, and from a similar human clinical procedure of therapeutic plasma exchange (TPE), revealed a molecular re-setting of the systemic signaling milieu, interestingly, elevating the levels of some proteins, which broadly coordinate tissue maintenance and repair and promote immune responses.”……followed by them saying, “A model of action (supported by a large body of published data) is that significant dilution of autoregulatory proteins that crosstalk to multiple signaling pathways (with their own feedback loops) would, through changes in gene expression, have long-lasting molecular and functional effects that are consistent with our observations.”

    So, look at supplementary table 1. The vast majority of protein expression that is of interest is up-regulated. Dilution of bad old-age proteins seems far less likely the mechanism of action than up-regulation of young-age proteins. The big questions should be why is this happening, what up/down regulation is significant to the rejuvenation process, and can we illicit this effect in some way other than plasma exchange. There is insufficient evidence to prove or disprove the “dilution theory” so hopefully further research is planned to look into this further.

    Interesting stuff. Thanks for sharing Mr. Wang

  50. It’s not clear to me how much plasma is collected in a donation. They backfill with saline, so it might be more than you think.

  52. If this works, wouldn’t you be able to retrospectively look at health of regular plasma donors and see if there is a difference? We’d have to control for the health status of those allowed and inclined to donate. Given that no one has noticed it yet, I imagine the effect is not huge, or maybe only because old people are less likely to donate plasma. Or the albumin is really important (plasma donations are typically backfilled with just saline, apparently).

  53. In Canada, whole blood donations are 450 mL. My average bleed time (helpfully tracked in the app) is 7 minutes. 45 minutes is mostly pre-screening and recovery time. Plasma donation is more like 1-2h.

  54. Maybe this is something that can be automated: Imagine laying down in your sleeping pod at night. A robot connects to your ‘Port’ (many people already get ports installed to make chemotherapy more simple, gives easy access to your bloodstream). The blood can flow through sensor arrays – plasma can be separated and removed – replaced with the saline/albumin solution and that and the other blood constituents flows right back in. Supplemented by additions that the analysis step determined might be needed. Or other ‘supplements’ that some marketing agency convinced you to try could also be pumped in. UV Sterilization and other hi tech cleaning techniques could keep the system clean and reliable for long periods of time before maintenance is necessary……All these robo-doc ideas have been thought of many times before of course, but this could be a simple system that might get things going.

  55. That will come, in the form of all the biotech and genetic methods currently being researched.

    But this one strikes me as a lower hanging fruit, which doesn’t mean it isn’t effective.

  56. Call me a crack pot or missing the forest through the trees but I’ll bet this helps with Hair loss, which seems increasingly related to something in the microvasculature near the hair follicles. Aging is obviously leagues more important..but why not have yet another highly monetizable avenue to bring it to the mainstream?
    It’d be interesting to see if these factors can be targeted in a similar manner to dialysis machine function

  57. Depends on the insurance company. If they’re just offering health insurance, or maybe life insurance, too, it looks like a cost effective way to reduce morbidity and mortality. So they’d likely cover it.

    If they’ve got substantial exposure in the pension market, they start to have a conflict of interest.

  58. Sounds like you can sign up for regular plasma donations to achieve the same thing for free, start today.

  59. A typical whole blood donation is 350 mL, takes 45 min. A plasma donation is probably similar in volume. Even if it’s larger, it’s likely not more than 500-600 mL. It takes 2 hours. Half your blood is 2.5-3 L, which is 5-10 times that volume. So yeah, you’ll be sitting there all day. Or more likely, you’ll have to come in more than once.

    The question is: How does the magnitude of the benefit vary with time after donation, as a function of the donation volume (two-parameter function: B(V,t) )? Is 1/4 enough? How about 1/10th?

  60. If it improves your overall health for a couple of months it’s still worth it doing it every quarter. Assuming it is cheap, which it could be.

  61. So, no magic juju in young people’s blood? just removing old people’s plasma and change it for clean artificial one has the same or better effects.

    Thankfully this also avoids turning old people into modern versions of vampires, and avoid having young people selling their blood to the old.

    But I guess this is better for everyone, given the therapy could become really common and relatively cheap.

  62. So – back to medieval leech therapy.
    We need more high tech solutions. Like living near a black hole or travelling at relativistic speed.

  63. Hmmmm….replacing half my blood plasma sounds like an ordeal – yet also a very simple procedure. Something that might not be accepted by the FDA quickly could be done in an underground medical clinic….might be worth keeping an eye out for. If anti-agathic medicine is suppressed by cumbersome bureaucracies, these clinics might start springing up (undoubtedly exist already – stem cell clinics seem pretty common). If those treatments actually start showing real successes, hopefully it will push mainstream medicine into pushing for the acceptance of proven treatments to combat the scourge of ageing. We all need this ASAP!

  65. IIRC in Heinlein’s “Methuselah’s Children” something of this sort was a major factor in the rejuvenation techniques that prolonged the lives of people who weren’t from the genetically long lived Howard Families.

  68. No, this is just plasma replacement, the cells stay in place. It’s removing soluble toxins. The question is what those toxins’ residence time is.

    It sounds to me like you could get some of the benefit of this by becoming a plasma donor; The albumin replacement is just to enable larger volume replacement.

    I suppose there are moral questions about donating plasma if you’re older, if it really is true your plasma is toxic. But but I believe the plasma is generally fractionated and used to supply specific factors for therapy, so maybe that’s not an issue.

  69. Whoa, I’m going to have to share this with my doctor. Finally a quite effective treatment I could probably obtain. In the mean while, I now have a strong motive to sign up for plasma donation.

    It’s been known for a while that transfusions from young donors had some serious benefits for elderly recipients. The question was whether it was supplementing factors the elderly patients weren’t producing enough of, or diluting toxins the elderly patients were producing too much of. This kind of settles the question: It’s the toxins.

    Probably spill-over from senescent cells in the tissues.

    This therapy is a LOT easier to pull off than the donation therapy, because the only thing incoming is albumin, electrolytes, and water. In theory albumin could be mass produced by cell cultures.

  70. Interesting. But will this not remove half of the immune cells of the blood as well? And leave the patient more susceptible for infections?

    And how long does the effect last?

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