High doses of synthetic antioxidants induce premature senescence in cultivated mesenchymal stem cells
High doses of synthetic antioxidants induce premature senescence in cultivated mesenchymal stem cells
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DOI：
10.1038/s41598-018-37972-y
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发表时间：
2019-02-04
影响因子：
4.6
通讯作者：
Lyublinskaya, O. G.
中科院分区：
文献类型：
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作者：
Kornienko, Ju. S.;Smirnova, I. S.;Lyublinskaya, O. G.
已知各种遗传毒性应激物在细胞中激活应激诱导的早衰程序，氧化应激被认为是其中主要的。为此，许多研究发现抗氧化剂作为保护性抗衰老剂。在当前的研究中，我们检查了不同抗氧化剂（Tempol、白藜芦醇、NAC、DPI）对维持在正常生理条件下的间充质干细胞的影响。我们使用了高剂量但无细胞毒性的抗氧化剂，这些抗氧化剂在实验室实践中广泛使用，以保护细胞免受氧化损伤。我们表明，这些物质诱导细胞增殖的可逆性阻滞，并没有造成任何遗传毒性作用时，适用于静止细胞。然而，相同剂量的相同物质，当应用于增殖细胞时，可以诱导不可逆的细胞周期停滞，DNA链断裂积累和DNA损伤反应激活。因此，抗氧化剂诱导的DNA损伤导致应激诱导的早衰程序激活。我们的结论是，高剂量的抗氧化剂，当应用于增殖细胞，保持生理水平的活性氧，可导致DNA损伤，诱导过早衰老，这表明重新估计相信无条件的抗衰老抗氧化剂的特性。
Stress-induced premature senescence program is known to be activated in cells by various genotoxic stressors, and oxidative stress is considered to be the main of those. To this end, many studies discover antioxidants as protective anti-aging agents. In the current study, we examined the effects of different antioxidants (Tempol, resveratrol, NAC, DPI) on the mesenchymal stem cells maintained in normal physiological conditions. We used high, but non-cytotoxic antioxidant doses which are widely used in laboratory practice to protect cells from oxidative damage. We show that these substances induce reversible block of cell proliferation and do not cause any genotoxic effects when applied to the quiescent cells. However, the same doses of the same substances, when applied to the proliferating cells, can induce irreversible cell cycle arrest, DNA strand breaks accumulation and DNA damage response activation. As a consequence, antioxidant-induced DNA damage results in the stress-induced premature senescence program activation. We conclude that high doses of antioxidants, when applied to the proliferating cells that maintain physiological levels of reactive oxygen species, can cause DNA damage and induce premature senescence which suggests to re-estimate believed unconditional anti-aging antioxidant properties.