Fig. 6.

The effect of repetitive TPE on aged blood. Aged blood has the characteristics of chronic inflammation (inflammaging), increased PBMC DNA damage and senescence, and immune deregulation, all changes that promote the high risk of diseases. TPE resets the systemic milieu to a younger state by rapidly and significantly diluting the age-elevated inhibitors of the canonical signaling pathways that regulate tissue maintenance and repair. The immediate effect is reduction of inflammation, and the subsequent effects are improvement in cellular and molecular homeostasis from calibrated cell–cell signaling crosstalks and reduction of biological noise that is defined in this study. Longitudinal studies allowed us to reveal novel broadly rejuvenative aspects of this seemingly simple procedure and to derive statistically significant conclusions with less samples than those needed in bulk comparisons. Created with BioRender.com