Multi-omics Analysis Reveals Biomarkers that Contribute to Biological Age Rejuvenation in Response to Therapeutic Plasma Exchange

The rapid increase in the proportion of older adults worldwide poses a huge challenge for healthcare systems. Currently, age-related chronic diseases account for over 90% of annual healthcare expenditures (more than $4.1 trillion) in the US alone. Thus, new therapies to improve healthspan and reduce the burden of chronic disease are needed. Herein, we conducted a phase 3 controlled clinical trial to evaluate the biological age (BA) effects of different therapeutic plasma exchange (TPE) modalities in ambulatory individuals. We longitudinally profiled the subjects to measure changes in the epigenome, proteome, metabolome, glycome, and shifts in immune cell composition (cytomics). We demonstrate that administering TPE supplemented with intravenous immunoglobulin (IVIG) (TPE-IVIG) on a biweekly regime (two sessions in the first week, followed by a three-week break) is a robust therapy for BA rejuvenation. This intervention induced coordinated cellular and molecular ‘omics’ responses, reversed age-related immune decline, and modulated key cellular senescence-associated proteins. Integrative analysis revealed baseline biomarkers associated with successful responses, indicating that TPE-IVIG treatment benefits those with a poorer baseline health status. In summary, this is the first multi-omics study to examine the effectiveness of various TPE modalities, which demonstrate biological age rejuvenation and the molecular features associated with this rejuvenation.