Humankind has been trying to figure out a way to rejuvenate older people by borrowing some youthful essence from the young for a very long time. The Old Testament describes a young virgin being rounded up to lie with King David so she could impart her warmth and moisture to the aged king, an approach which enjoyed scientific currency through the 17th century. The form of rejuvenation that is taking center stage at longevity conferences these days, therapeutic plasma exchange or TPE, has roots that go back to the mid-1800s. A French scientist developed a technique to stitch together two mice, an old one and a young one, their bodies pumping the same blood supply. The result? The old one appeared to grow younger, and the young one older, a finding that has been replicated with more precision in more recent “parabiosis” research done at Berkeley and Harvard, among other places.
It was only a matter of time before humans would attempt a similar rejuvenation, not stitching people together, but via infusion. Over the past decade, clinics have sprung up which infused blood plasma from young donors into the bodies of older clients, a decidedly risky business. While blood plasma lacks the red and white cells and platelets of whole blood, it contains plenty of proteins that play important biological roles in the body, as growth factors, hormones, antibodies, and more. Some clients appeared to have benefited, some have experienced immune reactions and other serious side-effects (in some cases, death), in all a crapshoot that prompted the FDA to warn about “unscrupulous actors” in the field.
Enter the San Francisco Bay Area company Global Apheresis and its founder immunologist Dobri Kiprov who is pioneering a more conservative, and much safer, form of plasma rejuvenation, therapeutic plasma exchange. In a handful of clinics around the country using his technology, blood plasma is removed from the patient, about 2-3 liters at each session, and then the fluid is replaced with a saline solution containing 5% albumin, the primary constituent of blood plasma. The albumin has been purified, so it carries only the relatively few proteins attached to the albumin macromolecule. Gone is the unpredictable stew of proteins that travel in the live-donor blood plasma. While the introduced albumin proteins appear to have a positive health effect, the major therapeutic benefit at this early stage of the therapy’s development is the removal of inflammatory molecules that travel the bloodstream. The older we get, the more senescent (aged, dysfunctional) cells we acquire which then spit out inflammatory factors, including usual suspects like IL-6 and TNF Alpha. As Kiprov framed it in the title of the 2022 paper detailing his collaboration with researchers from Berkeley and UCSF, “Old plasma dilution reduces human biological age.”
The beauty of this approach, from a safety and regulatory point of view, is that medicine has already been using it. For instance, physicians have for decades used plasma exchange, or plasmapheresis, to treat neurological autoimmune diseases like Guillain-Barre syndrome and myasthenia gravis. Kiprov’s novel approach was to dig deeper into the underlying biology, measuring the impact of the procedure on the molecular pathways of aging, from autophagy to inflammation and beyond.
TPE rejuvenation occurs at an epigenetic level, that is, by manipulating the chemical messengers which serve as the on/off switches determining which genes are activated and when. The factors that are withdrawn or introduced into the body (via albumin) directly affect that epigenome and hence profoundly influence how we age. Think of the blood in our system as a kind of biochemical record of how well or poorly we live. The stress we experience, the infections we suffer, the bad habits we indulge in (smoking, excessive drinking, etc.) all manifest in the make-up of these circulating factors, ditto, the good things we do, like exercise which generates health-promoting myokine proteins and peptides.
The TPE concept is straightforward and intuitively appealing (which is why the ancients were working on their own version of it). To wit, extract some bad things and introduce some good ones, or, if you like, take out some December and put in some May, such that the internal “milieu” of a 70-year-old might more closely resemble that of a 25-year-old who regularly exercises. But the details are devilishly complex. To try to unravel who would best benefit from TPE, and from which possible version of it, Kriprov has teamed up with the Buck Institute, the nation’s leading longevity research organization, to do the painstaking “-omics” analysis of the relevant molecules going in and out.
When treatments can be tailored to the individual patient and protocols established for the optimal number of treatments, then the hope is, we’ll see greater improvements in biomarkers and a greater reduction in “biological age.” (Kripov calculates a two-year drop in the biological age of the ten study patients who have undergone full-scale TPE, significant but not mind-blowing. Ditto the results from studies that have looked at TPE as an Alzheimer’s disease therapy.) There is also promising evidence that the metabolic benefits last longer than the lifespan of the proteins in question. It may be that TPE is not just akin to vacuuming the floor every time it gets dirty; it could be a way to build a more efficient vacuum cleaner.
I’m excited by the longevity breakthroughs that may be possible with TPE. We shall see. To date, none of my patients have tried it, although I’d be pleased if several of my elderly patients would consider it – the potential rewards would seem to greatly outweigh the risks. There is now a clinic in Manhattan that offers the therapy. I may just avail myself of TPE and get an experiential sense of what all the fuss is about.
Thyago R. Cardim-Pires et al. Healthy blood, healthy brain: a window into understanding and treating neurodegenerative diseases. Journal of Neurology 12 April 2024. doi.org/10.1007s00415-024-12337-w
Daehwan Kim, Dobri D. Kiprov, et al. Old plasma dilution reduces human biological age: a clinical study. GeroScience 2022 Dec; 44(6): 2701-2702. doi: 10.1007/s11357-022-00645-w
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