In a first, a randomized, placebo-controlled trial has been performed to assess the safety and effects on biological age of therapeutic plasma exchange (TPE) regimens in healthy adults over 50. Therapeutic plasma exchange is a procedure that separates, removes, and replaces patient plasma to treat certain diseases. Participants received bi-weekly TPE with or without intravenous immunoglobulin (IVIG), monthly TPE, or placebo. The results of the clinical trial suggest that TPE combined with intravenous immunoglobulin reduced biological age on average by 2.6 years. The output was measured by multiomic biomarkers.
The results of this work are published in Aging Cell, in the paper, “Multi-Omics Analysis Reveals Biomarkers That Contribute to Biological Age Rejuvenation in Response to Single-Blinded Randomized Placebo-Controlled Therapeutic Plasma Exchange.”
“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,” commented David Furman, PhD, an associate professor at the Buck Institute and director of the Institute’s Bioinformatics and Data Science Core.
The study, which included 42 participants, was led by scientists at Circulate Health and the Buck Institute for Research on Aging. The research 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.
Patients receiving TPE showed a reduction in biological age, as measured by multi-omics biomarkers, with the most significant reductions in those patients who 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.
“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.”
