Polymorphisms of the murine mitochondrial ND4, CYTB and COX3 genes impact hematopoiesis during aging.
During aging, mitochondrial DNA (mtDNA) can accumulate mutations leading to increasing levels of reactive oxygen species (ROS). Increased ROS were described to activate formerly quiescent hematopoietic stem cells (HSC). Mutations in mtDNA were shown to enhance the risk for myelodysplastic syndrome and leukemia. However, the complex relationship between mtDNA variations, ROS and aging of the hematopoietic system is not fully understood.Herein, three mouse strains with mtDNA polymorphisms in genes of respiratory chain complexes I (ND4), III (CYTB) and IV (COX3) were compared to a reference strain during aging. Analysis focused on ROS and ATP levels, bone marrow composition and blood counts. Additionally, hematopoietic restoration capacity following cytotoxic stress was tested.Mice with polymorphisms in ND4 and CYTB gene had significantly decreasing ROS levels in bone marrow cells during aging, without effecting ATP levels. In addition, the frequency of stem and progenitor cells increased during aging but the amount of lymphocytes in the peripheral blood decreased during aging.In summary, the presence of mtDNA polymorphisms affecting the respiratory chain complexes I, III and IV was associated with altered ROS levels as well as changes in BM and peripheral blood composition during aging.
Department of Medicine III - Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Christin
C
Kretzschmar
Department of Medicine III - Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Catrin
C
Roolf
Department of Medicine III - Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Katrin
K
Timmer
Department of Medicine III - Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Anett
A
Sekora
Department of Medicine III - Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Gudrun
G
Knübel
Department of Medicine III - Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Hugo
H
Murua Escobar
Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.
Georg
G
Fuellen
Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Saleh M
SM
Ibrahim
Institute of Medical Biochemistry and Molecular Biology, Rostock University Medical Center, Rostock, Germany.
Markus
M
Tiedge
Institute of Medical Biochemistry and Molecular Biology, Rostock University Medical Center, Rostock, Germany.
Simone
S
Baltrusch
Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock, Germany.
Robert
R
Jaster
Oscar Langendorff Institute of Physiology, Rostock University Medical Center, Rostock, Germany.
Rüdiger
R
Köhling
Department of Medicine III - Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Christian
C
Junghanss
D000255:Adenosine Triphosphate / Q000378:metabolism; D000367:Age Factors; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000378:metabolism; D014450:Electron Transport Complex III / Q000235:genetics*; D005260:Female; D055786:Gene Knockout Techniques; D050259:Genes, Mitochondrial; D006410:Hematopoiesis / Q000235:genetics*; D051379:Mice; D009245:NADH Dehydrogenase / Q000235:genetics*; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism
C098483:NADH dehydrogenase subunit 4; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3; D009245:NADH Dehydrogenase; D014450:Electron Transport Complex III
Gerotarget; ROS; aging; hematopoiesis; mtDNA; stem cell