Circulate Health and Buck researchers find that TPE combined with immunoglobulin reduced biological age by more than 2.5 years on average.
A clinical study published this week in Aging Cell suggests that therapeutic plasma exchange (TPE), can significantly reduce biological age, particularly when combined with intravenous immunoglobulin (IVIG). Conducted by TPE provider Circulate Health in collaboration with the Buck Institute for Research on Aging, the single-blind human trial is believed to be the first to assess the rejuvenative potential of TPE using comprehensive molecular profiling. Participants who underwent biweekly TPE with IVIG demonstrated an average reduction in biological age of 2.61 years, outperforming the 1.32-year reduction observed in those receiving TPE alone.
Backed by Khosla Ventures, Circulate is building on research led by Dr Dobri Kiprov, a pioneer in therapeutic plasma exchange for aging. The company is led by co-founders Dr Brad Younggren and Dr Eric Verdin, who is also president and CEO of the Buck Institute, and its FDA-cleared TPE system is already used in more than 20 functional health clinics across the US.
“In this study, we examined thousands of molecular signatures to pinpoint key drivers of rejuvenation,” said Verdin. “Our characterization builds a better understanding of which baseline biomarkers are predictive of treatment response and lays a foundation upon which we can build personalized intervention plans for patients in the future.”
Longevity.Technology: TPE, also known as plasmapheresis, involves circulating a patient’s blood through an apheresis machine that separates and removes plasma before replacing it with a substitute such as albumin or donor plasma. This process is designed to eliminate disease-promoting substances like autoantibodies, inflammatory proteins or toxins, many of which accumulate with age and contribute to age-related conditions. Already well-established in the treatment of several autoimmune and neurological disorders, TPE is now being explored for its applications in aging and longevity science. To learn more, we sat down with Dr Matt Kaeberlein, CEO of Optispan and affiliate professor at the University of Washington, who recently joined Circulate’s Scientific Advisory Board.
A renowned aging researcher himself, Kaeberlein says his decision to get involved in Circulate was driven by the company’s scientific credibility and a growing personal conviction about the promise of the technology.
“The fact that Eric Verdin from the Buck Institute is a co-founder, and David Furman is involved gives me a lot of confidence that this is being approached from a scientifically rigorous perspective,” he says. “Eric and David are fantastic scientists – I have a ton of respect for them – and the fact that they’re doing these kinds of studies bears that out. So I have confidence that the company really is trying to do this in the right way.”
Kaeberlein ‘bullish’ on TPE
Beyond the people involved, the growing body of scientific evidence supporting TPE’s potential also played a role in Kaeberlein’s decision.
“Over the last 12 to 18 months, I personally have become much more bullish on the technology of therapeutic plasma exchange,” he says. “This comes in part from the preclinical literature in laboratory animals showing that you can both increase lifespan and improve function in a variety of aged tissues and organs, and then the small but growing data from human studies and small clinical trials.”
The recent trial studied 42 participants aged over 50 to explore how different TPE regimens affected biological aging markers across the epigenome, proteome, metabolome, glycome, and immune system. Physical function measures such as balance and strength were also included.
“The study was primarily a safety evaluation, but also with the goal of looking at whether TPE can have effects on biological age clocks based on multi-omic types of data,” explains Kaeberlein. “I thought it was interesting that they tested both with and without intravenous immunoglobulin, and also the fact that they looked at multiple types of omics data instead of just using epigenetic clocks.”
TPE reduced biological age in all groups
The study found that, among all treatment groups, TPE led to measurable reductions in biological age, with the most pronounced effects seen in the group receiving both TPE and IVIG. The combined treatment also restored immune cell profiles typically altered with age, modulated proteins associated with cellular senescence, and appeared to improve immune resilience.
“There was evidence for improvements in a variety of these multi-omic biological age estimates – all consistent with the idea that therapeutic plasma exchange is moving biomarkers of health in the right direction,” says Kaeberlein. “And there was a trend that the IVIG added some value.”
The study found that individuals in poorer baseline health experienced the most significant benefits. Participants with elevated bilirubin, glucose, or liver enzyme levels saw larger decreases in biological age and improvements in their health markers. Even among healthier participants, the treatment yielded gains in physical performance.
“Our findings show that plasma exchange and intravenous immunoglobulin are a powerful tool for biological age rejuvenation and provide compelling evidence that targeted plasma interventions can impact age-related molecular changes,” said Circulate CEO Younggren in a statement.
It should be noted that the data also indicated that the most substantial benefits occurred after the initial three treatment sessions, with subsequent rounds offering diminished returns. The researchers believe the pattern suggests future protocols might improve outcomes by adjusting treatment frequency or combining TPE with complementary therapies.
Potential in inflammation and neurodegeneration
Kaeberlein was also careful to note the study’s limitations, including the small size of the cohorts, a point also noted by the study’s authors, who intend to expand the research to “larger populations.” And, while he says more research is needed to determine effect size, he adds that “the limited data that I’ve seen is suggestive that, at least in those populations who are likely to be strong responders, the effect size is significant.”
When it comes to the long-term potential of TPE, Kaeberlein is clearly optimistic, particularly in areas like chronic inflammation and neurodegeneration.
“I’m pretty bullish on the likelihood that some sort of therapeutic plasma exchange – perhaps in combination with IVIG, or even in combination with delivering other factors as part of the TPE – is likely to have health benefits, at least for a subset of people,” he says. “The people who are the most obvious candidates are those with high levels of chronic, sterile inflammation, or people who are either at high risk for dementia or who are already on that path with mild cognitive impairment.”
In fact, so convinced is Kaeberlein, that he is about to see for himself what TPE can deliver.
“I’m actually going to be doing my first round of therapeutic plasma exchange on Wednesday of this week, and will be doing some biomarker comparisons before and after,” he says. “As someone who tends to be pretty conservative relative to some other people in this field about endorsing interventions, I would say I’m cautiously optimistic.”
Photographs courtesy of Circulate Health.
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