Therapeutic plasma exchange combined with intravenous immunoglobin reduces biological age

A first-of-its-kind clinical trial clinical trial shows that therapeutic plasma exchange (TPE) combined with intravenous immunoglobin reduced biological age on average by 2.6 years, as measured by multi-omic biomarkers. Results of the single-blind, placebo-controlled trial are published in the May 28, 2025, issue of Aging Cell, providing early data on the impact of TPE on biological age, supporting its potential for new disease and longevity applications. The research was led by scientists at Circulate Health, a company dedicated to harnessing the potential of TPE to advance human healthspan and lifespan, and the Buck Institute for Research on Aging. 

Unfortunately, most so-called 'longevity interventions' lack proven effectiveness in humans. By conducting clinical trials, we aim to change that-this study marks the first step in demonstrating that plasma exchange can significantly improve key mechanisms of biological aging."

David Furman, PhD, senior author of the study and Buck associate professor and director of the Institute's Bioinformatics and Data Science Core

Therapeutic plasma exchange is a procedure that separates, removes, and replaces patient plasma to treat certain diseases. The study , investigated how TPE impacts biomarkers associated with biological age, including changes across the epigenome, proteome, metabolome, glycome, and immune system, alongside physical measures like balance and strength. Research participants were assigned one of four different treatment groups: 1) biweekly TPE, 2) biweekly TPE with intravenous immunoglobulin (IVIG) 3) monthly TPE or 4) a control group.

The study found:

• Patients receiving TPE showed a reduction in biological age, as measured by multi-omics biomarkers, with the most significant reductions in those patients that received TPE with IVIG. Participants undergoing biweekly TPE-IVIG treatment exhibited an average biological age reduction of 2.61 years, compared to 1.32 years for those receiving TPE alone.
• Patients receiving TPE with IVIG experienced changes in immune cells associated with reversed age-related immune decline. This intervention modulated cellular senescence-associated proteins and restored age-associated shifts in immune cell composition. This indicates that TPE with IVIG may improve the body's ability to fight infections and other age-related diseases, particularly those related to inflammation.
• Individuals with biomarkers associated with poorer baseline health status, including higher baseline levels of circulating bilirubin, glucose, and liver enzymes, saw the greatest reduction in biological age and improvement in biomarkers. The treatment also showed a benefit for healthy individuals, including balance and strength.
• While the observed treatment effects were strongest after the initial three sessions, subsequent treatments showed diminishing returns, suggesting that spacing out treatments or combining them with other interventions may enhance long-term benefits.

"This is the first interventional multi-omics study to examine the effectiveness of therapeutic plasma exchange modalities," said Brad Younggren, MD, CEO and Co-founder of Circulate. "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."

"In this study, we examined thousands of molecular signatures to pinpoint key drivers of rejuvenation. 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," said Eric Verdin, MD, President and CEO of the Buck Institute and Co-founder of Circulate. "We are excited to expand our research to larger populations, increase access to these treatments for eligible patients, and continue to identify areas of unmet need where these therapies can make a meaningful difference."