title: Uncoupling protein 2 deficiency results in higher neutrophil counts and lower B-cell counts during aging in mice.
abstract: Progress of age-related hematopoietic diseases such as myelodysplastic syndrome has previously been linked to enhanced levels of reactive oxygen species (ROS). Uncoupling protein 2 (UCP2) was found to reduce mitochondrial ROS production through uncoupling of the respiratory chain. The impact of UCP2 loss and elevated ROS on hematopoiesis during aging has not yet been investigated. In this study, UCP2 knockout mice were analyzed at aging stages of 3, 12, and 24 months with respect to oxidative and energy status of bone marrow cells. Further, the cellular bone marrow subpopulation composition was characterized, as were the differential blood counts at all time points. UCP2 knockout mice revealed enhanced levels of mitochondrial superoxide in elderly animals. Following oxidative stress, adenosine triphosphate (ATP) levels decreased more in the knockout mice than in the wild type. Investigation of bone marrow and blood counts of the knockout mice revealed an enhanced amount of monocytes and neutrophils, as well as a decreased amount of B cells and impaired erythropoiesis throughout aging. In summary, UCP2 induces protective effects on ROS and ATP levels during aging. Additionally, the results suggest an imbalance in hematopoiesis because of the lack of UCP2.
authors.affiliation: Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Kretzschmar
authors.affiliation: Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
authors.forename: Catrin
authors.initials: C
authors.lastname: Roolf
authors.affiliation: Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Timmer
authors.affiliation: Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
authors.forename: Anett
authors.initials: A
authors.lastname: Sekora
authors.affiliation: Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Knübel
authors.affiliation: Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
authors.forename: Hugo
authors.initials: H
authors.lastname: Murua Escobar
authors.affiliation: Division of Gastroenterology, Department of Medicine II, Rostock University Medical Center, Rostock, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Jaster
authors.affiliation: Division of Gastroenterology, Department of Medicine II, Rostock University Medical Center, Rostock, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Müller
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Fuellen
authors.affiliation: Oscar Langendorff Institute of Physiology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Köhling
authors.affiliation: Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany. Electronic address: Christian.Junghanss@med.uni-rostock.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Junghanss
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics; D016130:Immunophenotyping; D007958:Leukocyte Count; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D000071246:Uncoupling Protein 2 / Q000172:deficiency*
chemical_list: D015415:Biomarkers; D000071246:Uncoupling Protein 2; D000255:Adenosine Triphosphate