Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food, and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel.
Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, D-70599 Stuttgart, Germany.
Int J Mol Sci. 2022 May 20;23(10):5750. doi: 10.3390/ijms23105750.
Mesenchymal stem cells (MSC) have many roles that are important for the body's proper functioning. When the MSC pool is damaged, it is often correlated with impaired development or health of the organism. MSC are known for their anti-inflammatory, immunomodulatory and trophic characteristics that play an important role in the physiological homeostasis of many tissues. Heat shock impairs MSC capacity by inducing the generation of reactive oxygen species and mitochondrial dysfunction, which, in turn, send the cells into a state of premature senescence. Here, we pre-exposed MSC to melatonin, resveratrol, or curcumin, which are natural antioxidative compounds, and tested the protective effects of these substances from oxidative stress and aging. Our data showed that pre-exposure of MSC to antioxidants decreased reactive oxygen species while mitochondrial damage remained high. Additionally, although the proliferation of the cells was slow, antioxidants protected the cells from premature senescence, and subsequent cytokine release was prevented. We conclude that while elevated temperatures directly cause mitochondrial damage, senescence is induced by elevated ROS levels. We suggest that heat shock alters cell and tissue homeostasis by several independent mechanisms; however, reducing tissue senescence will reduce damage and provide a pathway to overcome physiological challenges in animals.
间充质干细胞 (MSC) 具有许多对身体正常功能至关重要的作用。当 MSC 池受损时，通常与机体发育或健康受损有关。MSC 以其抗炎、免疫调节和营养特性而闻名，这些特性在许多组织的生理稳态中起着重要作用。热休克通过诱导活性氧的产生和线粒体功能障碍来损害 MSC 的能力，这反过来又使细胞进入过早衰老的状态。在这里，我们预先将 MSC 暴露于褪黑素、白藜芦醇或姜黄素中，这些都是天然抗氧化化合物，并测试了这些物质对氧化应激和衰老的保护作用。我们的数据表明，MSC 预先暴露于抗氧化剂可以降低活性氧，同时保持线粒体损伤。此外，尽管细胞的增殖缓慢，但抗氧化剂可以保护细胞免受过早衰老，从而防止随后细胞因子的释放。我们得出的结论是，虽然高温会直接导致线粒体损伤，但衰老却是由升高的 ROS 水平引起的。我们认为，热休克通过几种独立的机制改变细胞和组织的稳态；然而，减少组织衰老将减少损伤，并为动物克服生理挑战提供途径。
