Regenerative biologics
Therapeutic plasma exchange (plasmapheresis for aging)
Graded on: epigenetic clocks A test that estimates biological age from chemical marks on DNA (DNA methylation). and circulating biomarkers A measurable sign in the body, such as a blood test value, used to track a condition or the effect of a treatment. of aging.
Grade C: human trials exist, but they are small, mixed or not yet repeated. This is not a finding that it does not work. How to read a grade →
Compare this record with another, side by side →
How this letter has changedLatest: October 2026 · Corrected.
grade_basis counted Borsky et al. (2025; PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 40592961) as a second positive randomized trial of plasma exchange; it tested plasma removal without replacement, randomized only between 8 and 4 sessions with no untreated control, and reported GrimAge, the Hannum clock and the Dunedin pace of aging increasing. The ref now states that finding and that it does not replicate plasma exchange. Fuentealba et al. (2025; PMID 40424097) is now described as single-blinded with allocation by entry date in the ref's first sentence, and the record discloses that one author co-founded a company that sells plasma exchange, with no specific funding declared. C unchanged. Applied the written grade definition under the editor's standing instruction of October 2026 (Arnold Sandlow, D.C.).PMID 40424097 PMID 40592961
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Plasma exchange removes the liquid part of the blood and replaces it. It is promoted as an anti-aging treatment. One small study of 42 adults found that blood tests meant to estimate body age moved younger, mostly in a group that also got an immune treatment. A different procedure in another study moved those tests the wrong way. No study shows people feel or function better.
A letter describes the human evidence, not the product, the manufacturer, or the intervention's worth.
See the full evidence record →Graded on Epigenetic clocks and circulating biomarkers of aging.
Why this gradeGrade C, small or unreplicated trials. The reasoning, and what the grade does not cover.
Grade C. One small trial tested plasma exchange against sham A fake version of a procedure or device used as the comparison, so participants cannot tell which one they received. (Fuentealba et al., 2025; PMID 40424097): 42 adults, single-blinded, allocated by entry date rather than random assignment, with epigenetic clocks moving toward younger values, strongest in the arm that also received intravenous immunoglobulin. The only other human trial (Borsky et al., 2025; PMID 40592961) tested a different procedure, plasma removal without replacement, 8 against 4 sessions with no untreated control, and found the clocks moving the wrong way, so it does not replicate plasma exchange. Every endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. is a surrogate: epigenetic clocks, circulating biomarkers, immune cell composition. Surrogate-only signals cap at B under the EBL rubric, and one unreplicated pilot-scale trial is C.
WHAT AN EPIGENETIC CLOCK ISa model trained to predict chronological age and mortality across populations. Moving one has not been shown to change what happens to a person. Nothing here reports a clinical outcome, and the safety finding, which is the more solid result of the two, is not a benefit finding.
WHAT THIS GRADE DOES NOT COVERthe arm the larger trial reports as most effective combined plasma exchange with intravenous immunoglobulin, so the effect cannot be attributed to plasma exchange on its own. That trial was single-blinded and allocated participants by entry date rather than by true random assignment, both of which weaken it further, and one of its authors co-founded a company that sells plasma exchange. The other human trial, of plasma removal without replacement, reported epigenetic age accelerating rather than reversing. Neither trial reports a clinical outcome, so nothing here speaks to survival, disability, frailty, cognition or cardiovascular events. And the letter grades evidence, not procedure risk: this is an invasive extracorporeal procedure carrying the hazards that come with vascular access, citrate anticoagulation and replacement fluids, among them hypotension, hypocalcemia, bleeding, infection, and reactions to the replacement fluid or to immunoglobulin. Two participants among the 42 discontinued for adverse events, one of them related to the immunoglobulin.
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An extracorporeal procedure requiring vascular access, not a supplement. The cited trial reported long-term plasma exchange as safe in 42 healthy adults over 50, with two adverse events requiring discontinuation, one of them related to the intravenous immunoglobulin arm. Forty-two participants is the whole of the safety evidence, and it cannot detect an uncommon harm.
The evidence, in fullTwo papers, each linked to its PubMed record.
Fuentealba et al. (Aging Cell, 2025; PMID 40424097): single-blinded placebo-controlled trial in 42 healthy adults over 50, comparing bi-weekly plasma exchange with or without intravenous immunoglobulin, monthly exchange, and placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received.; allocation was by entry date rather than true random assignment. Primary objectives were long-term safety and change in biological clocks; the procedure was reported safe, with two adverse events requiring discontinuation, one related to the immunoglobulin, and 15 epigenetic clocks moved toward younger values against placebo. The regimen reported as most effective combined bi-weekly exchange with intravenous immunoglobulin. One author is co-founder and chief scientific officer of Circulate Inc., a company offering plasma exchange, and two others are members of it; no specific funding is declared. Borsky et al. (Sci Rep, 2025; PMID 40592961): a different procedure, plasma removal without replacement fluid, in healthy blood donors randomized to 8 or 4 sessions over 18 weeks with no untreated control; no epigenetic rejuvenation, and GrimAge, the Hannum clock and the Dunedin pace of aging increased, with lipids and serum proteins lower. It does not replicate plasma exchange and its direction is unfavorable. Grade C: one small, single-blinded, non-randomly allocated positive trial on surrogate clocks, unreplicated.
Nothing validated. Epigenetic clock scores are the endpoint these trials moved, and they are markers rather than outcomes.
Evidence notes: randomized trial, pilot study, not independently replicated The same finding reproduced by a separate research group. A result seen once can be chance or bias; a replicated one is harder to explain away., non random allocation
Endpoint graded: Epigenetic clocks and circulating biomarkers of aging (surrogate)
Last reviewed: August 2026
Educational use only · Not medical advice · EBL grades published human evidence and does not recommend treatment. Stopping a prescription is a decision for your physician.
Primary evidenceTwo papers, each linked to its PubMed record.
Fuentealba et al. (Aging Cell, 2025; PMID 40424097): single-blinded placebo-controlled trial in 42 healthy adults over 50, comparing bi-weekly plasma exchange with or without intravenous immunoglobulin, monthly exchange, and placebo; allocation was by entry date rather than true random assignment. Primary objectives were long-term safety and change in biological clocks; the procedure was reported safe, with two adverse events requiring discontinuation, one related to the immunoglobulin, and 15 epigenetic clocks moved toward younger values against placebo. The regimen reported as most effective combined bi-weekly exchange with intravenous immunoglobulin. One author is co-founder and chief scientific officer of Circulate Inc., a company offering plasma exchange, and two others are members of it; no specific funding is declared. Borsky et al. (Sci Rep, 2025; PMID 40592961): a different procedure, plasma removal without replacement fluid, in healthy blood donors randomized to 8 or 4 sessions over 18 weeks with no untreated control; no epigenetic rejuvenation, and GrimAge, the Hannum clock and the Dunedin pace of aging increased, with lipids and serum proteins lower. It does not replicate plasma exchange and its direction is unfavorable. Grade C: one small, single-blinded, non-randomly allocated positive trial on surrogate clocks, unreplicated.
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("plasma exchange"[tiab] OR plasmapheresis[tiab]) AND (aging[tiab] OR "biological age"[tiab] OR epigenetic[tiab]) AND (randomized controlled trial[pt] OR clinical trial[pt]) AND humans[mesh]Grades move when new trials publish. A free monthly email lists every grade EBL moved, with the reason and the trial behind it: the sign-up is on the Evidence Log →