title: Endogenous ROS levels are increased in replicative senescence in human bone marrow mesenchymal stromal cells.
abstract: Cellular senescence is characterized by functional decline induced by cumulative damage to DNA, proteins, lipids, and carbohydrates. Previous studies have reported that replicative senescence is caused by excessive amounts of reactive oxygen species (ROS) produced as a result of aerobic energy metabolism. In this study, we established human bone marrow mesenchymal stromal cells (hBM-MSCs) in replicative senescence after culture over a long term to investigate the relationship between ROS levels and stem cell potential and to determine whether differentiation potential can be restored by antioxidant treatment. Intracellular ROS levels were increased in hBM-MSCs; this was accompanied by a decrease in the expression of the antioxidant enzymes catalase and superoxide dismutase (SOD)1 and 2 and of phosphorylated forkhead box O1 (p-FOXO1) as well as an increase in the expression of p53 and p16, along with a reduction in differentiation potential. When the antioxidant ascorbic acid was used to eliminate excess ROS, the levels of antioxidant enzymes (catalase, SOD1 and 2, p-FOXO1, and p53) were partly restored. Moreover, differentiation into adipocytes and osteocytes was higher in hBM-MSCs treated with ascorbic acid than in the untreated control cells. These results suggest that the decline in differentiation potential caused by increased endogenous ROS production during in vitro expansion can be reversed by treatment with antioxidants such as ascorbic acid.
authors.affiliation: Department of Biology, College of Natural Science, Chosun University, Gwangju 501-759, Republic of Korea; Department of Life Science, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Sin-Gu
authors.initials: SG
authors.lastname: Jeong
authors.affiliation: Department of Biology, College of Natural Science, Chosun University, Gwangju 501-759, Republic of Korea; Department of Life Science, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju 501-759, Republic of Korea. Electronic address: gwcho@chosun.ac.kr.
authors.forename: Goang-Won
authors.initials: GW
authors.lastname: Cho
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D016922:Cellular Senescence; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; D001205:Ascorbic Acid
keywords: Antioxidant enzyme; Mesenchymal stromal cells (MSCs); Reactive oxygen species (ROS); Replicative senescence