Reactive oxygen species produced in mitochondria are involved in age-dependent changes of hematopoietic and mesenchymal progenitor cells in mice. A study with the novel mitochondria-targeted antioxidant SkQ1
Reactive oxygen species produced in mitochondria are involved in age-dependent changes of hematopoietic and mesenchymal progenitor cells in mice. A study with the novel mitochondria-targeted antioxidant SkQ1
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DOI：
10.1016/j.mad.2010.06.003
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发表时间：
2010-06-01
影响因子：
5.3
通讯作者：
Skulachev, V. P.
中科院分区：
文献类型：
--
作者：
Shipounova, I. N.;Svinareva, D. A.;Skulachev, V. P.
用有效的靶向抗氧化剂SkQ 1 [10-（6 '-plastoquinonyl）decyltriphenylphosphonium]终身治疗小鼠不会影响造血干细胞（HSC）和更分化的造血祖细胞，但会显著减缓外周血中的年龄依赖性变化。在前13个月，SkQ 1（0.9或28.8 nmol/kg/天）可防止年龄依赖性骨髓转移（粒细胞比例增加和淋巴细胞比例减少）。在下一年的治疗期间，效果消失，2岁治疗小鼠的血象与对照组没有差异。在用SkQ 1治疗的2年期间，骨髓中的间充质干细胞（MSC）的数量没有改变，但是MSC后代成纤维细胞集落形成单位（CFU-F）的浓度随着SkQ 1的剂量而增加。用SkQ 1治疗1年和2年后的CFU-F浓度是年轻小鼠的两倍。我们的数据表明，造血细胞的基质环境可能是线粒体中产生的活性氧介导的年龄依赖性变化的主要靶点。这里描述的SkQ 1的抗衰老作用与在其他模型中观察到的这种抗氧化剂对衰老的抑制作用完全一致。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Lifelong treatment of mice with the effective mitochondria-targeted antioxidant SkQ1 [10-(6'-plastoquinonyl) decyltriphenylphosphonium] does not affect hematopoietic stem cells (HSC) and more differentiated hematopoietic progenitors but significantly decelerates age-dependent changes in peripheral blood. During the first 13 months, SkQ1 (0.9 or 28.8 nmol/kg day) prevents age-dependent myeloid shift (increase in the proportion of granulocytes and decrease in the proportion of lymphocytes). During the next year of treatment the effect disappears, and the hemogram of 2-year-old treated mice does not differ from the control. The number of mesenchymal stem cells (MSC) in the bone marrow does not change during 2 years of treatment with SkQ1, but the concentration of MSC progeny fibroblast colony-forming units (CFU-F) increases with dose of SkQ1. The concentration of CFU-F after 1 and 2 years treatment with SkQ1 is twice higher than in young mice Our data indicate that the stromal environment of hematopoietic cells could be the primary target of age-dependent changes mediated by reactive oxygen species produced in mitochondria. The anti-aging effects of SkQ1 described here are in perfect agreement with the inhibitory effects of this antioxidant on aging observed in the other models. (C) 2010 Elsevier Ireland Ltd. All rights reserved.