Plasmapheresis for longevity

Scientific overview

Previously in 2016 A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood, blood was exchanged from young mice to old, and vice-versa. Highlight is the fact that old blood appears to contain factors which actively suppress rejuvenation. One such example is the inhibition of stem cells: when muscle stem cells are cultured in old blood, almost not a single one proliferates; and when the plasma of the old blood is diluted, they regain their function (see 2019 Conboy paper mentioned below). Transfusion of old blood had this effect even in otherwise young and healthy subjects. Conversely, young blood does not contain any instrinsic factors which can effectively mitigate this suppression, or otherwise stimulate rejuvenation again, if given to already aged subjects.

One theory for the accumulation of those factors in old blood is that they are being produced by tissue which gets damaged over time and then they propagate systemically in the rest of the body, dragging all the other organs down as well. This is partly suggested by the fact that tissue damage inflicted on young mice further amplified the systemic suppression caused by receiving old blood.

In 2019 Undulating changes in human plasma proteome profiles across the lifespan, a study screened plasma proteins in people of all ages and tracked when the levels of those proteins had a strong variance across a +/- 5 years interval window. They found that there are three significant points when plasma composition shifts significantly, before stabilizing again for a while in the new state (Fig 3c). The first one is around the age of 35.

In 2020 Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin, Irina and Michael Conboy discovered that plasmapheresis lowered multiple biomarkers of aging. The procedure consisted of replacing one volume of blood plasma (i.e 50-60%) with a neutral solution (saline + albumin). The consequence of doing this is a significant dilution of circulating proteins in the plasma. It is hypothesised that many of those proteins play signaling roles and that the therapeutic benefit emerges from interrupting signaling feedbacks. By having to secrete new signals following the procedure, the body has an opportunity to adjust their ratios and transitions spontaneously into a different steady state. Compared to manually tweaking individual signals, this process appears to be natural and self-adaptive. A rudimentary mathematical model was also used to demonstrate how steady states can arise and how interrupting the feedback loops can trigger a state transition. A further paper by the Conboys in 2022, Old plasma dilution reduces human biological age: a clinical study, showed through a small clinical trial that plasmapheresis once monthly for 6 months provided a cumulative improvement in aging biomarkers.


Plasmapheresis, also known as apheresis, is an old, well-established and safe procedure. It consists of blood being passed to a plasmapheresis machine, then centrifuged to separate plasma from cells and finally returned to the patient with some of the original plasma removed. The main risk, albeit rare, is that of triggering coagulation, due to blood leaving the closed-circuit of the circulatory system and making contact with the artificial surfaces of the device. Haemonetics is a popular supplier of low-cost, portable plasmapheresis units, which have been known to be resold occasionally on secondary market. Replacing removed plasma with a neutral saline + albumin solution appears to be optional: the Conboys demonstrated that the therapeutic benefit does not depend on the addition of exogenous, "fresh" albumin. The body is able to restore the volume of lost plasma quickly, provided sufficient hydration and dietary protein.

Unfortunately, plasmapheresis is FDA-approved only for specific conditions, such as auto-immune disorders. There are currently very limited options for obtaining the procedure off-label. In the US, the Maxwell Clinic currently offers it privately for an exorbitant price. The Conboys are working towards patenting a modified plasmapheresis method that they will offer through their startup, IMYu. Dobri Kiprov, the clinical consultant who collaborated with the Conboys, has also offered his consulting services to clinics interested in offering the procedure (it's hard to tell whether his insight actually provides better results over standard plasmapheresis); he has his own upcoming venture, Lyfspn. So far, clinical trials have only accepted middle-aged (50+) volunteers. Plasma blood donations are probably inadequte, because the limit for one donation is way below the volume required by the protocol (60%) and they also limit how often you are allowed to do it per week/month; therefore, it is unlikely that plasma donations, as currently regulated, will achieve sufficient dilution of plasma proteins. Either way, the procedure requires at the very minimum access to a plasmapheresis machine and a nurse trained in phlebotomy. As usual, it could be worthwhile to find clinics in developing countries who will provide the intervention at a considerable discount; but also with the downside of travelling costs and the risk of dangerous incompetence.

Further Reading