Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Laboratory of Flow Cytometry, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy.
Cells. 2023 Feb 22;12(5):691. doi: 10.3390/cells12050691.
Life on Earth has evolved in the presence of a gravity constraint. Any change in the value of such a constraint has important physiological effects. Gravity reduction (microgravity) alters the performance of muscle, bone and, immune systems among others. Therefore, countermeasures to limit such deleterious effects of microgravity are needed considering future Lunar and Martian missions. Our study aims to demonstrate that the activation of mitochondrial Sirtuin 3 (SIRT3) can be exploited to reduce muscle damage and to maintain muscle differentiation following microgravity exposure. To this effect, we used a RCCS machine to simulate microgravity on ground on a muscle and cardiac cell line. During microgravity, cells were treated with a newly synthesized SIRT3 activator, called MC2791 and vitality, differentiation, ROS and, autophagy/mitophagy were measured. Our results indicate that SIRT3 activation reduces microgravity-induced cell death while maintaining the expression of muscle cell differentiation markers. In conclusion, our study demonstrates that SIRT3 activation could represent a targeted molecular strategy to reduce muscle tissue damage caused by microgravity.
地球上的生命是在存在重力约束的情况下进化的。这种约束值的任何变化都会对生理产生重要影响。重力降低(微重力)会改变肌肉、骨骼和免疫系统等的性能。因此,需要考虑未来的月球和火星任务,采取对策来限制微重力的这种有害影响。我们的研究旨在证明激活线粒体 Sirtuin 3(SIRT3)可用于减少微重力暴露后肌肉损伤并维持肌肉分化。为此,我们使用 RCCS 机器在地面上模拟微重力对肌肉和心肌细胞系的影响。在微重力条件下,用新合成的 SIRT3 激活剂 MC2791 处理细胞,并测量细胞活力、分化、ROS 和自噬/线粒体自噬。我们的结果表明,SIRT3 的激活可减少微重力诱导的细胞死亡,同时维持肌肉细胞分化标志物的表达。总之,我们的研究表明,SIRT3 的激活可能代表一种针对分子策略,可减少微重力引起的肌肉组织损伤。