Multi-omics Analysis Reveals Biomarkers That Contribute to Biological Age Rejuvenation in Response to Single-Blinded Randomized Placebo-Controlled Therapeutic Plasma Exchange
clinical paper · 2025
LINK
SUMMARY
The central clinical trial publication for the TPE-IVIG case. Single-blind randomized placebo-controlled study of 42 healthy adults over 50 across four arms (biweekly TPE alone, biweekly TPE+IVIG, monthly TPE alone, saline placebo) with six treatment sessions over approximately three months. Primary outcomes measured across a panel of 35 epigenetic clocks (Horvath, PhenoAge, GrimAge, DunedinPACE, Systems Age, and others). Results: biweekly TPE+IVIG -2.61 years (FDR=6.22e-05); monthly TPE -1.32 years (FDR=2.42e-02); biweekly TPE alone less than monthly; placebo showed age acceleration. Systems Age clocks: immune -9.7 years, inflammatory -7.1 years in TPE-IVIG arm. Two adverse events required discontinuation. The paper states the authors received no specific funding for the work; the disclosed conflict of interest is that Furman, Verdin, and Kiprov are Circulate, Inc. members (Verdin and Kiprov co-founders), with technology support acknowledged from Edifice Health. Open-access; full text available at the Wiley link.
NOTES
The Fuentealba et al. paper is the canonical primary source for the TPE-IVIG case. The trial methodology is substantially more rigorous than the historical precedents in this archive (randomized, placebo-controlled, single-blind, multi-omics outcome measurement, false-discovery-rate correction across the multi-clock panel). The methodological strengths sit alongside the structural conflict: the paper states the authors received no specific funding for the work, but the principal investigators are members of the commercializing company (Circulate, Inc.), the paper acknowledges technology support from Edifice Health, and the primary finding is being deployed in marketing of the commercial service at the time of writing. The paper is the appropriate citation for any discussion of the TPE-IVIG protocol’s evidence base and the appropriate starting point for evaluating the case.