Feeling bad blood? Get rid of that old man plasma

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From stitched-together mice to Matt Kaeberlein’s apheresis chair

In late May, social media was blessed with an image of biogerontologist and rapamycin expert Matt Kaeberlein flashing a victory sign from a clinic chair. Dominating the foreground was a transparent collection bag, half-filled with - to use a polite euphemism - a rich, yellow-gold fluid: Kaeberlein’s own plasma, separated by an apheresis machine.

The procedure, known as therapeutic plasma exchange (TPE), was performed by Circulate Health, a startup in which Kaeberlein is an investor.

“I had my first go at therapeutic plasma exchange this morning”, Kaeberlein wrote on X.

“Look at all that old man plasma they squeezed out of me 😅 In all seriousness, I'm very optimistic about this approach both for potential positive effects on aging biology and for the possibility of diluting out environmental toxins such as microplastics. Procedure was super easy. Hardest part was sitting still for 2 1/2 hours.”

Kaeberlein isn’t one to jump on hype trains - which, at least for me, has the effect that it only makes TPE more exciting than it already was. Still, it’s too early to say what role plasma exchange might play in the broader quest to slow or reverse aging. What’s clear is that this line of research has deep roots - stretching back at least to the 1950s.

And it starts with something called parabiosis.

Parabiosis - the surgical fusion of two animals so they share a single circulatory system - sounds as if it belongs on a Fangoria cover or in a Mary Shelley novel, yet the procedure is entirely real. The word itself comes from the Greek for “living beside.”

French physiologist Paul Bert first performed the operation on two laboratory rats in the 1860s, perhaps inspired by the renowned conjoined twins Chang and Eng Bunker, whose fame gave rise to the term “Siamese twins.”

Paul Bert proved that the stitched rats naturally merged their circulatory systems, a finding that earned him accolades from the French Academy of Sciences. Despite the fanfare, the technique slipped into obscurity for decades. Only in the mid-20th century did scientists revive parabiosis as a powerful investigative tool. Since then, researchers have run thousands of such experiments to probe diabetes, transplant rejection, cancer, obesity, and a host of other conditions.

Parabiosis has sometimes yielded real breakthroughs. Between 1969 and 1973, Douglas Coleman at Jackson Laboratory in Bar Harbor, Maine, stitched together genetically obese mice, diabetic mice and their lean littermates. He reasoned that either a factor in the lean mouse’s blood would rescue the diabetic, or the healthy animal would succumb to whatever plagued its partner.

What happened was stranger: the diabetic mouse stayed morbidly obese, while its lean companion abruptly stopped eating and died of starvation. Repeating the experiment convinced Coleman that the obese mutant was spewing an extraordinarily powerful satiety signal into the shared bloodstream. (In a complementary experiment, pairing an obese mutant to a lean mouse caused the obese animal to slim down, showing the opposite effect.)

Few colleagues bought the idea - until 1994, when Jeffrey Friedman identified the hormone leptin, confirming Coleman’s hunch and cementing parabiosis in the history of metabolic science.

In the 1950s, calorie-restriction pioneer Clive McCay tried a different frontier: he surgically joined aged rats to young ones. The project produced no headline-worthy data, yet - like his earlier low-calorie-diet work - it sowed an idea that later took root as “heterochronic parabiosis.”

By the 1970s, other scientists showed that elderly rats outlived their peers simply by sharing blood with younger animals, but the result barely nudged mainstream geroscience. Real momentum arrived only in the past two decades, driven by the attention-grabbing experiments of Irina and Michael Conboy.

Modern biogerontology often drills down to molecules inside and around cells, a focus that can obscure the larger system. The Conboys’ studies re-centered the conversation: an organism’s overall internal milieu can reshape individual tissues - just as global events can reverberate through everyday life.

Because stem-cell reserves dwindle with age, Irina and Michael Conboy asked whether an old mouse’s regenerative capacity could be rekindled by sharing blood with a young partner. In their landmark 2005 Nature study, they showed that aged mice joined to juveniles repaired injured muscle and regenerated liver tissue as efficiently as youthful controls - the same old cells, re-energised by a youthful systemic milieu. Later work extended the effect to the brain.

The brain is, in fact, what catapulted parabiosis into the modern spotlight. In 2011, Saul Villeda and Tony Wyss‑Coray showed that young mice joined to aged partners experienced a sharp fall in hippocampal neurogenesis and memory, implicating blood‑borne “pro‑aging” factors.

Three years later the same group flipped the setup: brief infusions of young plasma rejuvenated synaptic plasticity and restored maze learning in old mice, proving that circulating signals can also drive brain repair.

Together, those studies convinced many sceptics that “young blood” could reach the brain and reset its circuitry.

In 2023, this line of thinking got its strongest support yet. A 3-month heterochronic parabiosis study from Vadim Gladyshev’s lab at Harvard showed that old mice stitched to young ones not only reversed multiple aging clocks by ~30%, but also lived about 10% longer - and the rejuvenation effects persisted for weeks after detachment.

Media outlets have often leaned into “vampire” tropes, and about ten years ago start-ups began selling young-plasma infusions - an unproven therapy that eventually drew the ire of the FDA.

Transfusing “young blood” into older adults remains an unproven - and, according to repeated FDA warnings, potentially risky - procedure. The ‘vampire’ theme has also unfairly tainted the broader study of heterochronic parabiosis.

And, notably, Irina and Michael Conboy later proposed that rejuvenation might stem less from youthful factors than from diluting pro-ageing components in old plasma. Some of their follow-up work confirmed this: in “neutral blood exchange,” researchers filter out aged plasma - no young blood required - and the treated mice show striking improvements.

In mouse studies, neutral plasma exchange has restored muscle repair, improved liver function, and rejuvenated hippocampal tissue - all without a single drop of young blood.

To loop back to Matt Kaeberlein: the hospital analogue is, as mentioned above, therapeutic plasma exchange (TPE), a type of plasmapheresis in which your plasma is removed and discarded while your own blood cells are returned together with an albumin-saline substitute.

All forms of plasmapheresis use the same bedside centrifuge or membrane filter, so the patient simply reclines in the familiar apheresis chair for two-to-three hours.

And, just as Kaeberlein was finishing his session, news broke of a new study on TPE. Published in Aging Cell, the trial reported that a monthly course of plasma exchange - combined with intravenous immunoglobulin (IVIG) - rolled back biological age by an average of 2.6 years, according to multiple epigenetic clocks. Participants also showed signs of immune rejuvenation. However, the longer-term durability of the effect remains untested and will require a larger, longer study to confirm.

The study was conducted by Circulate Health, the same company handling Kaeberlein’s plasma, in partnership with the Buck Institute for Research on Aging.

There’s bound to be bad blood in life - that’s just how it goes. But at least this kind can literally be washed away, half a litre at a time.