摘要：SummaryUnderstanding the mechanisms for cellular aging is a fundamental question in biology. Normal red blood cells (RBCs) survive for approximately 100 days, and their survival is likely limited by functional decline secondary to cumulative damage to cell constituents, which may be reflected in altered metabolic capabilities. To investigate metabolic changes duringin vivoRBC aging, labeled cell populations were purified at intervals and assessed for abundance of metabolic intermediates using mass spectrometry. A total of 167 metabolites were profiled and quantified from cell populations of defined ages. Older RBCs maintained ATP and redox charge states at the cost of altered activity of enzymatic pathways. Time-dependent changes were identified in metabolites related to maintenance of the redox state and membrane structure. These findings illuminate the differential metabolic pathway usage associated with normal cellular aging and identify potential biomarkers to determine average RBC age and rates of RBC turnover from a single blood sample.Graphical AbstractDisplay OmittedHighlights•Altered glycolytic, amino acid, and fatty acid metabolism occurs in normal RBC aging•GSH pools are maintained in spite of age-dependent shifts in enzyme synthesis•Changes in choline and GPC suggest alterations in membrane lipid metabolism•Ophthalmate, GPC, and ergothioneine are candidate metabolic clocks for RBC agingMedical Biochemistry; Metabolomics
