Hsu Wei-Bin, Lin Shih-Jie, Hung Ji-Shiuan, Chen Mei-Hsin, Lin Che-Yi, Hsu Wei-Hsiu, Hsu Wen-Wei Robert
Sports Medicine Center, Chang Gung Memorial Hospital Chiayi Branch, Puzi, Taiwan.
Department of Orthopaedic Surgery, New Taipei City Municipal Tucheng Hospital, New Taipei City, Taiwan.
Bone Joint Res. 2022 Feb;11(2):121-133. doi: 10.1302/2046-3758.112.BJR-2021-0079.R2.
The decrease in the number of satellite cells (SCs), contributing to myofibre formation and reconstitution, and their proliferative capacity, leads to muscle loss, a condition known as sarcopenia. Resistance training can prevent muscle loss; however, the underlying mechanisms of resistance training effects on SCs are not well understood. We therefore conducted a comprehensive transcriptome analysis of SCs in a mouse model.
We compared the differentially expressed genes of SCs in young mice (eight weeks old), middle-aged (48-week-old) mice with resistance training intervention (MID+ T), and mice without exercise (MID) using next-generation sequencing and bioinformatics.
After the bioinformatic analysis, the PI3K-Akt signalling pathway and the regulation of actin cytoskeleton in particular were highlighted among the top ten pathways with the most differentially expressed genes involved in the young/MID and MID+ T/MID groups. The expression of , , and in the PI3K-Akt signalling pathway was higher in the young and MID+ T groups compared with the MID group. Similarly, , , and in the regulation of the actin cytoskeleton pathway had a similar bias. Moreover, the protein expression profiles of , and in each group were paralleled with the results of NGS.
Our results revealed that age-induced muscle loss might result from age-influenced genes that contribute to muscle development in SCs. After resistance training, age-impaired genes were reactivated, and age-induced genes were depressed. The change fold in these genes in the young/MID mice resembled those in the MID + T/MID group, suggesting that resistance training can rejuvenate the self-renewing ability of SCs by recovering age-influenced genes to prevent sarcopenia. Cite this article: 2022;11(2):121-133.
卫星细胞(SCs)数量减少以及其增殖能力下降会导致肌肉流失,即肌肉减少症,而卫星细胞有助于肌纤维的形成和重建。抗阻训练可以预防肌肉流失;然而,抗阻训练对卫星细胞影响的潜在机制尚不清楚。因此,我们在小鼠模型中对卫星细胞进行了全面的转录组分析。
我们使用下一代测序和生物信息学方法,比较了年轻小鼠(8周龄)、接受抗阻训练干预的中年小鼠(48周龄,MID+T)和未运动的中年小鼠(MID)卫星细胞中差异表达的基因。
经过生物信息学分析,PI3K-Akt信号通路以及肌动蛋白细胞骨架的调节在年轻/MID组和MID+T/MID组中差异表达基因最多的前十条通路中尤为突出。与MID组相比,PI3K-Akt信号通路中 、 和 的表达在年轻组和MID+T组中更高。同样,肌动蛋白细胞骨架调节通路中的 、 和 也有类似的偏向。此外,每组中 、 和 的蛋白质表达谱与NGS结果平行。
我们的结果表明,年龄诱导的肌肉流失可能源于影响卫星细胞肌肉发育的年龄相关基因。抗阻训练后,年龄受损的基因被重新激活,年龄诱导的基因被抑制。年轻/MID小鼠中这些基因的变化倍数与MID+T/MID组相似,这表明抗阻训练可以通过恢复受年龄影响的基因来恢复卫星细胞的自我更新能力,从而预防肌肉减少症。引用本文:2022;11(2):121-133。