Plasmapheresis is a medical procedure that separates plasma from blood cells, potentially removing pro-aging factors from circulation. Some studies suggest it may have rejuvenating effects by altering biomarkers of aging, but evidence on its impact on epigenetic aging in humans is limited. This study aimed to assess whether plasmapheresis without volume replacement with young plasma or albumin affects epigenetic age and other biomarkers in healthy adults. An automatic plasma collection system, the Haemonetics PCS2, was used for plasmapheresis. Healthy blood donors were divided into two groups using stratified randomization in a cross-over study with subjects undergoing either 8 plasmaphereses (8 pp) or 4 plasmaphereses (4 pp) for an 18-week period, with a minimum interval between plasmaphereses of 2 weeks (14 days). Samples were tested for biochemical, hematological analyses and epigenetic clocks. We documented the alteration in serum minerals, decreased serum lipids, mainly total cholesterol, non-HDL, triglycerides, apolipoprotein A levels, total proteins and albumin. Among hematologic parameters, we found an increase in Red Cell Distribution Width (RDW) and Mean Corpuscular Hemoglobin Concentration (MCHC). No significant epigenetic rejuvenation was observed based on epigenetic clock measurements. Instead, plasmapheresis was associated with increases in DNAmGrimAge, the Hannum clock, and the Dunedin Pace of Aging. Plasmapheresis can rapidly change the levels of pro-inflammatory and other pro-aging molecules in the circulation. However, the selected protocol has not provided conclusive data supporting benefits. Based on epigenetic clock parameters, it may accelerate epigenetic aging. More research into the long-term safety of this specific protocol is needed.
Borsky P. et al. “Human clinical trial of plasmapheresis effects on biomarkers of aging (efficacy and safety trial).”* Scientific Reports 15, 21059 (1 July 2025).
Why the study was done
Background. In animal work, exchanging or removing plasma can blunt pro-aging signals and rejuvenate tissues. Whether a straight plasmapheresis session (no albumin or “young” plasma replacement) does the same in people was unknown.
Goal. Test if repeated plasma donations alter biochemical markers, haematology and—crucially—DNA-methylation “epigenetic clocks,” the most widely used molecular read-outs of biological age. (nature.com)
How the trial worked
Feature
Details
Design
18-week, randomised cross-over in healthy first-time donors (Czech Republic)
Groups
G1 (n ≈ 28) – eight plasmapheresis sessions (every 2 weeks) • G2 (n ≈ 13) – four sessions (same schedule but first 9 weeks serve as control), then groups crossed over
Device
Haemonetics PCS2 automated system; 750 mL plasma typically removed per visit
Ages
40–60 y; 34 participants completed all visits
End-points
Standard chemistry, lipids, minerals, full blood count, vitamin D, and six epigenetic clocks (Horvath DNAmAge, PhenoAge, SkinBloodAge, GrimAge, Hannum, DunedinPACE)
Key findings
Domain
Main changes (post-intervention)
Lipids
↓ Total-C, ↓ non-HDL-C, ↓ triglycerides, ↓ Apo A
Proteins & minerals
↓ Total protein, ↓ albumin; shifts in Ca²⁺/Mg²⁺ consistent with citrate exposure
Haematology
↑ RDW, ↑ MCHC (sub-clinical but statistically significant)
Epigenetic clocks
No rejuvenation; in fact ↑ DNAmGrimAge, ↑ HannumAge, ↑ DunedinPACE—signals of accelerated biological ageing
Hormonal/metabolic surrogates
DNAm surrogates for PAI-1, COX and pack-years ↑; leptin surrogate ↓
No participant experienced serious adverse events, but several withdrew for unrelated health exclusions. (nature.com)
Authors’ interpretation
The two-week donation cadence that many commercial centres use is safe in the immediate term but does not deliver epigenetic rejuvenation and may even push ageing biomarkers in the wrong direction.
Lipid lowering is a clear “side benefit,” yet falls in albumin and total protein could carry longer-term risks.
Albumin replacement, longer intervals, or selective removal protocols might mitigate the apparent acceleration of epigenetic age.
Short follow-up (18 weeks) cannot reveal durable harms or benefits.
Seasonality & lifestyle confounding (trial ran spring–summer; no objective activity or diet logs).
No albumin/top-up infusion, so results apply only to “straight” donation protocols.
Take-away
Straight plasmapheresis may quickly lower atherogenic lipids but, under an every-two-weeks schedule without albumin replacement, it fails to slow—and may actually hasten—epigenetic ageing signatures. Clinically meaningful rejuvenation will likely require modified protocols; routine bi-weekly plasma donation for anti-ageing cannot be recommended on the basis of these data.
In this episode of Longevity by Design, Dr. Gil Blander welcomes Dr. Eric Verdin, President and CEO of the Buck Institute for Research on Aging. Eric discusses the science behind therapeutic plasma exchange (TPE) and its potential to slow biological aging in humans. The conversation explores findings from a recent clinical trial, including measurable age reversal using epigenetic clocks.
Eric explains how removing and replacing plasma can dilute pro-aging factors in the blood, a concept inspired by earlier animal studies on parabiosis. He also describes why rigorous, placebo-controlled human trials are crucial for validating longevity interventions and distinguishing the field from hype-driven wellness trends.
The episode also highlights how omics data, such as metabolomics and proteomics, are shaping a new era of precision aging research. Eric emphasizes the value of lifestyle interventions as a foundation and sees future opportunities in combining TPE with personalized strategies to extend healthspan."
AI Summary:
Introduction to Longevity by Design
The podcast “Longevity by Design” aims to provide listeners with access to leading scientific information in the field of longevity, focusing on how to enhance both lifespan and healthspan.
Dr. Gil Blander, the host, emphasizes the importance of scientific evidence over opinion in discussions about longevity and health.
Each episode features Dr. Blander alongside industry experts to explore key questions related to living longer and healthier lives.
Guest Introduction: Dr. Eric Verdin
Dr. Eric Verdin is introduced as a world-renowned neuroscientist and the president and CEO of the Buck Institute for Research on Aging, which is the first independent research center in the U.S. dedicated exclusively to aging biology.
His educational background includes training as a physician at the University of Leech and Harvard Medical School, and he has held significant roles at the NIH, UCSF, and the Gladstone Institute.
Dr. Verdin’s research focuses on epigenetic regulation and metabolic signals, examining their impact on immune aging and age-related diseases like Alzheimer’s.
Therapeutic Plasma Exchange Study Background
The discussion begins with Dr. Verdin explaining the rationale behind studying therapeutic plasma exchange (TPE), which is a medically approved procedure that involves removing blood plasma and reinfusing blood cells with a fresh solution.
The concept of heterochronic parabiosis, where two mice of different ages are surgically joined to share blood circulation, is referenced as foundational research that has sparked interest in the effects of young blood on aging.
Early studies suggested that factors in young blood could rejuvenate older mice, leading to speculation about similar effects in humans through TPE.
Clinical Trial Design and Methodology
The clinical trial included several arms: bi-weekly TPE, bi-weekly TPE plus immunoglobulin, monthly TPE, and a placebo group, with the aim of assessing the efficacy and safety of these interventions.
Dr. Verdin clarifies that the trial was designed to address questions regarding the frequency and effectiveness of TPE, as well as the potential side effects associated with the procedure.
The study aimed to apply rigorous scientific standards to validate the efficacy of TPE as a treatment for aging-related issues, contrasting it with many unproven supplements and interventions currently available.
Findings and Implications of the Study
The results indicated that TPE could lead to significant biological age reversals, with the most profound effects observed in participants receiving TPE plus immunoglobulin.
Dr. Verdin highlights the importance of understanding the biological markers that predict who might benefit the most from TPE, as some individuals showed more pronounced improvements than others.
The study also raised questions about the optimal frequency of TPE and the duration of its benefits, suggesting that further research is needed to refine the treatment protocol.
Future Directions and Considerations
Dr. Verdin discusses the future of TPE, suggesting that while it currently involves a broad removal of plasma, future advancements may lead to more targeted approaches that isolate and eliminate specific harmful molecules associated with aging.
He emphasizes the need for individuals to optimize their lifestyle choices before considering TPE, as these foundational health practices can significantly impact overall well-being.
The conversation concludes with a call for further research and funding in the field of longevity, highlighting the potential for new discoveries to transform healthcare and aging.
