Tarum Janelle, Degens Hans, Turner Mark D, Stewart Claire, Sale Craig, Santos Lívia
Department of Sport Science, Sport Health and Performance Enhancement Research Centre (SHAPE), School of Science and Technology, Nottingham Trent University, Nottingham, UK.
Musculoskeletal Science and Sports Medicine Research Centre, Department of Life Sciences, Manchester Metropolitan University Institute of Sport, Manchester Metropolitan University, Manchester, UK.
J Tissue Eng Regen Med. 2023 Jul 4;2023:9802235. doi: 10.1155/2023/9802235. eCollection 2023.
Healthy skeletal muscle can regenerate after ischaemic, mechanical, or toxin-induced injury, but ageing impairs that regeneration potential. This has been largely attributed to dysfunctional satellite cells and reduced myogenic capacity. Understanding which signalling pathways are associated with reduced myogenesis and impaired muscle regeneration can provide valuable information about the mechanisms driving muscle ageing and prompt the development of new therapies. To investigate this, we developed a high-throughput model to assess muscle regeneration in chemically injured C2C12 and human myotube-derived young and aged myoblast cultures. We observed a reduced regeneration capacity of aged cells, as indicated by an attenuated recovery towards preinjury myotube size and myogenic fusion index at the end of the regeneration period, in comparison with younger muscle cells that were fully recovered. RNA-sequencing data showed significant enrichment of KEGG signalling pathways, PI3K-Akt, and downregulation of GO processes associated with muscle development, differentiation, and contraction in aged but not in young muscle cells. Data presented here suggest that repair in response to injury is impaired in aged vs. young muscle cells. Our study establishes a framework that enables further understanding of the factors underlying impaired muscle regeneration in older age.
健康的骨骼肌在缺血、机械或毒素诱导的损伤后能够再生，但衰老会损害这种再生潜力。这在很大程度上归因于卫星细胞功能失调和肌生成能力降低。了解哪些信号通路与肌生成减少和肌肉再生受损相关，可以为驱动肌肉衰老的机制提供有价值的信息，并促进新疗法的开发。为了对此进行研究，我们开发了一种高通量模型，以评估化学损伤的C2C12以及人肌管衍生的年轻和衰老成肌细胞培养物中的肌肉再生。我们观察到衰老细胞的再生能力降低，与完全恢复的年轻肌肉细胞相比，在再生期结束时，向损伤前肌管大小和肌生成融合指数的恢复减弱。RNA测序数据显示，KEGG信号通路、PI3K-Akt在衰老肌肉细胞中显著富集，而与肌肉发育、分化和收缩相关的GO过程在衰老肌肉细胞中下调，在年轻肌肉细胞中则不然。此处呈现的数据表明，与年轻肌肉细胞相比，衰老肌肉细胞对损伤的修复能力受损。我们的研究建立了一个框架，能够进一步了解老年肌肉再生受损的潜在因素。
