The loss of peroxiredoxin 2 in mice disrupts the biochemical aging phenotype in erythrocytes

Biochemical aging involves progressive declines in energy metabolism and redox maintenance. The peroxiredoxin enzyme family is critical for maintenance of cellular redox states. In mice, enucleate mature red blood cells (RBCs) persist for roughly 50 days, providing an ideal system for tracking cellular aging <i>in vivo</i>. To define the impact of impaired redox function, we analyzed the RBC metabolome across defined cellular ages using biotin labeling to isolate populations at approximately 1, 2, and 3 weeks. A total of 183 metabolites were quantified by mass spectrometry. Overall metabolic trajectories were similar between wild-type and Prdx2-deficient RBCs, with age-associated shifts involving ATP-generating pathways, redox maintenance processes, and membrane-structure-related reactions. However, these metabolic changes were consistently more pronounced in Prdx2 knockout RBCs, indicating accelerated disruption of pathways linked to energy production and redox balance. These findings indicate that Prdx2 is essential for maintaining metabolic homeostasis during RBC aging.