Adult mesenchymal stem cell ageing interplays with depressed mitochondrial Ndufs6
| العنوان: | Adult mesenchymal stem cell ageing interplays with depressed mitochondrial Ndufs6 |
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| المؤلفون: | Hung-Fat Tse, Dan Jiang, Xiaoting Liang, Yimei Hong, Yuelin Zhang, Jinqiu Zhang, Bin Yan, Liyan Guo, Ling Chen, Zhao Zhang, Can Liao, Shuo Han, Cheng Li, Jianxiang Qiu, Xin Li, Xiaoya Zhou, Qizhou Lian, Xiaoxian Zhang, Shilong Zhong |
| المصدر: | Cell Death and Disease, Vol 11, Iss 12, Pp 1-15 (2020) Cell Death & Disease |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Mitochondrial ROS, Senescence, Cancer Research, Immunology, Down-Regulation, Bone Marrow Cells, Biology, Article, Mitochondrial Proteins, Cellular and Molecular Neuroscience, Downregulation and upregulation, Animals, Humans, RNA, Messenger, lcsh:QH573-671, Cellular Senescence, NDUFS6, lcsh:Cytology, Mesenchymal stem cell, Cell Differentiation, Mesenchymal Stem Cells, NADH Dehydrogenase, Cell Biology, Mitochondria, Stem-cell research, Cell biology, Mice, Inbred C57BL, Adult Stem Cells, Protein Subunits, Ageing, Gene Knockdown Techniques, Reactive Oxygen Species, Intracellular, Signal Transduction, Adult stem cell |
| الوصف: | Mesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy to treat many degenerative diseases. Accumulating evidence shows that the function of MSCs declines with age, thus limiting their regenerative capacity. Nonetheless, the underlying mechanisms that control MSC ageing are not well understood. We show that compared with bone marrow-MSCs (BM-MSCs) isolated from young and aged samples, NADH dehydrogenase (ubiquinone) iron-sulfur protein 6 (Ndufs6) is depressed in aged MSCs. Similar to that of Ndufs6 knockout (Ndufs6−/−) mice, MSCs exhibited a reduced self-renewal and differentiation capacity with a tendency to senescence in the presence of an increased p53/p21 level. Downregulation of Ndufs6 by siRNA also accelerated progression of wild-type BM-MSCs to an aged state. In contrast, replenishment of Ndufs6 in Ndufs6−/−-BM-MSCs significantly rejuvenated senescent cells and restored their proliferative ability. Compared with BM-MSCs, Ndufs6−/−-BM-MSCs displayed increased intracellular and mitochondrial reactive oxygen species (ROS), and decreased mitochondrial membrane potential. Treatment of Ndufs6−/−-BM-MSCs with mitochondrial ROS inhibitor Mito-TEMPO notably reversed the cellular senescence and reduced the increased p53/p21 level. We provide direct evidence that impairment of mitochondrial Ndufs6 is a putative accelerator of adult stem cell ageing that is associated with excessive ROS accumulation and upregulation of p53/p21. It also indicates that manipulation of mitochondrial function is critical and can effectively protect adult stem cells against senescence. |
| اللغة: | English |
| تدمد: | 2041-4889 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f5472c7302e79d095174f5d3fa135b8 https://doaj.org/article/513bd64b4ee342efbdc276847a31fa2a |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2f5472c7302e79d095174f5d3fa135b8 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 20414889 |
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