A groundbreaking clinical trial has demonstrated that therapeutic plasma exchange (TPE) combined with intravenous immunoglobulin can reverse biological aging, with participants showing an average reduction of 2.6 years in biological age as measured by comprehensive molecular biomarkers. The single-blind, placebo-controlled study, published in the May 28, 2025 issue of Aging Cell, represents the first interventional multi-omics investigation of TPE's effectiveness on biological aging mechanisms.
The research, led by scientists at Circulate Health and the Buck Institute for Research on Aging, examined how TPE impacts biomarkers associated with biological age across multiple biological systems, including the epigenome, proteome, metabolome, glycome, and immune system, alongside physical measures like balance and strength.
Study Design and Treatment Groups
Research participants were randomly assigned to one of four treatment groups: biweekly TPE, biweekly TPE with intravenous immunoglobulin (IVIG), monthly TPE, or a control group. The study design allowed researchers to compare different treatment frequencies and combinations to determine optimal therapeutic approaches.
Significant Biological Age Reduction
The most striking results emerged from the biweekly TPE-IVIG treatment group, which exhibited an average biological age reduction of 2.61 years compared to 1.32 years for those receiving TPE alone. This nearly two-fold improvement suggests that the combination therapy provides synergistic benefits beyond either treatment individually.
"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, senior author of the study and Buck associate professor and director of the Institute's Bioinformatics and Data Science Core.
Immune System Rejuvenation
Patients receiving TPE with IVIG experienced significant changes in immune cells associated with reversed age-related immune decline. The intervention modulated cellular senescence-associated proteins and restored age-associated shifts in immune cell composition, indicating that TPE with IVIG may improve the body's ability to fight infections and other age-related diseases, particularly those related to inflammation.
Baseline Health Status Predicts Response
The study revealed important insights about treatment response patterns. 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. However, the treatment also demonstrated benefits for healthy individuals, including improvements in balance and strength.
Treatment Optimization Insights
An important finding related to treatment scheduling emerged from the data. While the observed treatment effects were strongest after the initial three sessions, subsequent treatments showed diminishing returns. This suggests that spacing out treatments or combining them with other interventions may enhance long-term benefits, providing crucial guidance for future therapeutic protocols.
Clinical Implications and Future Directions
"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."
The comprehensive molecular analysis examined thousands of molecular signatures to identify key drivers of rejuvenation. According to Eric Verdin, MD, President and CEO of the Buck Institute and Co-founder of Circulate, "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."
Therapeutic Mechanism
Therapeutic plasma exchange is an established medical procedure that separates, removes, and replaces patient plasma to treat certain diseases. The current study expands the potential applications of this technology beyond its traditional uses, demonstrating its capacity to influence fundamental aging processes at the molecular level.
The research team plans to expand their investigations to larger populations and increase access to these treatments for eligible patients while continuing to identify areas of unmet need where these therapies can make a meaningful difference. The study's multi-omics approach provides a robust foundation for understanding the biological mechanisms underlying the observed age-reversal effects and developing personalized treatment strategies.
