#1

https://www.nature.com/articles/s41598-025-05396-0

Abstract

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.

2 Likes
#2

O3 summary

Citation & context

  • 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.

Limitations to keep in mind

  1. Small, homogeneous cohort (n = 34 finishers; all 40-60 y) limits generalisability.
  2. Short follow-up (18 weeks) cannot reveal durable harms or benefits.
  3. Seasonality & lifestyle confounding (trial ran spring–summer; no objective activity or diet logs).
  4. 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.

3 Likes
#3

These results are consistent with the (first?) paper looking at impact on biological age, though different protocol. No or negative effect.

1 Like