title: Biomarkers defining the metabolic age of red blood cells during cold storage.
abstract: Metabolomic investigations of packed red blood cells (RBCs) stored under refrigerated conditions in saline adenine glucose mannitol (SAGM) additives have revealed the presence of 3 distinct metabolic phases, occurring on days 0-10, 10-18, and after day 18 of storage. Here we used receiving operating characteristics curve analysis to identify biomarkers that can differentiate between the 3 metabolic states. We first recruited 24 donors and analyzed 308 samples coming from RBC concentrates stored in SAGM and additive solution 3. We found that 8 extracellular compounds (lactic acid, nicotinamide, 5-oxoproline, xanthine, hypoxanthine, glucose, malic acid, and adenine) form the basis for an accurate classification/regression model and are able to differentiate among the metabolic phases. This model was then validated by analyzing an additional 49 samples obtained by preparing 7 new RBC concentrates in SAGM. Despite the technical variability associated with RBC processing strategies, verification of these markers was independently confirmed in 2 separate laboratories with different analytical setups and different sample sets. The 8 compounds proposed here highly correlate with the metabolic age of packed RBCs, and can be prospectively validated as biomarkers of the RBC metabolic lesion.
authors.affiliation: Center for Biomedicine, European Academy of Bozen/Bolzano, Bolzano, Italy;
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paglia
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, University of Colorado Denver, Aurora, CO;
authors.forename: Angelo
authors.initials: A
authors.lastname: D'Alessandro
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland;
authors.forename: Óttar
authors.initials: Ó
authors.lastname: Rolfsson
authors.affiliation: The Blood Bank, Landspitali-University Hospital, Reykjavik, Iceland; School of Science and Engineering, Reykjavik Unversity, Reykajvik, Iceland; and.
authors.forename: Ólafur E
authors.initials: ÓE
authors.lastname: Sigurjónsson
authors.affiliation: Sinopia Biosciences, San Diego, CA.
authors.forename: Aarash
authors.initials: A
authors.lastname: Bordbar
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland; Sinopia Biosciences, San Diego, CA.
authors.forename: Sirus
authors.initials: S
authors.lastname: Palsson
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, University of Colorado Denver, Aurora, CO;
authors.forename: Travis
authors.initials: T
authors.lastname: Nemkov
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, University of Colorado Denver, Aurora, CO;
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Hansen
authors.affiliation: The Blood Bank, Landspitali-University Hospital, Reykjavik, Iceland;
authors.forename: Sveinn
authors.initials: S
authors.lastname: Gudmundsson
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland;
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Palsson
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001793:Blood Preservation / Q000379:methods*; D003080:Cold Temperature; D004905:Erythrocyte Aging / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D012044:Regression Analysis; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers