Fuentealba · Aging cell 2025 · single-blinded randomized placebo-controlled trial · n=42

Multi-Omics Analysis Reveals Biomarkers That Contribute to Biological Age Rejuvenation in Response to Single-Blinded Randomized Placebo-Controlled Therapeutic Plasma Exchange.

Cited 19 times in the scientific literature.

Level 2 - randomized trial

Individual randomized placebo-controlled trial

PubMed 40424097 · doi:10.1111/acel.70103 · record verified 2026-08-26

What was done

Healthy adults over 50 years old were enrolled in a single-blinded, placebo-controlled trial with randomization based on entry date (n = 42). Participants received biweekly therapeutic plasma exchange (TPE) with or without intravenous immunoglobulin (IVIG), monthly TPE, or placebo. Primary objectives assessed long-term safety and biological age alterations using epigenetic clocks. Longitudinal multi-omics profiling evaluated changes across the epigenome, proteome, metabolome, glycome, cytokines, iAge, and immune cell subsets.

What was found

Long-term TPE was reported safe, with two adverse events leading to discontinuation (one related to IVIG). TPE significantly improved biological age markers, with 15 epigenetic clocks showing rejuvenation compared to placebo (FDR < 0.05). Biweekly TPE with IVIG was the most effective regimen, reversing age-related immune decline and modulating chronic inflammation proteins. Baseline biomarkers predicted positive outcomes, showing greater benefit in individuals with poorer baseline health. Exact effect sizes and numerical values were not reported in the abstract.

Why it matters

This study provides randomized multi-omics evidence that therapeutic plasma exchange, particularly when combined with IVIG, can alter surrogate epigenetic clocks and immune aging biomarkers in older adults.

Limits

The sample size was small (42 participants across multiple treatment arms and placebo). Randomization was based on entry date rather than standard sequence generation, single-blinding was used, and outcomes were surrogate molecular markers rather than hard clinical endpoints.

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