O'Leary Mary, Greed Elsa, Pritchard Jack, Struszczak Lauren, Bozbaş Esra, Bowtell Joanna
Faculty of Health and Life Sciences, Department of Public Health and Sport Sciences, University of Exeter, Exeter, Devon, UK.
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
Exp Physiol. 2025 Mar;110(3):438-453. doi: 10.1113/EP092328. Epub 2024 Dec 11.
Resistance training (RT) is the gold standard intervention for ameliorating sarcopenia. Outstanding mechanistic questions remain regarding the malleability of the molecular determinants of skeletal muscle function in older age. Discovery of proteomics can expand such knowledge. We aimed to compare the effect of RT on the skeletal muscle proteome and neuromuscular function (NMF) in older and younger women. Seven young (22 ± 6 years) and eight older (63 ± 5 years) women completed 8 weeks' leg RT. Pre- and post-training, measures of leg and handgrip strength, NMF and vastus lateralis (VL) biopsies were obtained. Tandem-mass-tagged skeletal muscle proteomic analyses were performed. Data were analysed using differential expression and weighted gene co-expression network approaches. Proteins related to skeletal muscle contraction were lower in older skeletal muscle; this was not normalised by RT. Following RT, older women had higher expression of VL mitochondrial biogenesis proteins compared to the young, a reversal of pre-training observations. Seventy proteins were differentially expressed between age groups. VL expression of these proteins in older women was consistently and significantly associated with poorer leg strength/NMF. Conversely, VL expression of these proteins in older women was often associated with greater handgrip strength. This study has identified important differences in the molecular responses of young and old skeletal muscle to RT. We have demonstrated their close relationship with skeletal muscle function. Proteins that are refractory to RT may represent targets to ameliorate sarcopenia. We have described a 'proteomic-function' relationship that appears to be muscle-specific. Future research should further unpick these complex relationships.
抗阻训练（RT）是改善肌肉减少症的金标准干预措施。关于老年骨骼肌功能分子决定因素的可塑性，仍存在突出的机制问题。蛋白质组学的发现可以扩展此类知识。我们旨在比较RT对老年和年轻女性骨骼肌蛋白质组和神经肌肉功能（NMF）的影响。7名年轻女性（22±6岁）和8名老年女性（63±5岁）完成了为期8周的腿部抗阻训练。在训练前后，分别测量腿部和握力、神经肌肉功能，并获取股外侧肌（VL）活检样本。进行串联质量标签骨骼肌蛋白质组分析。使用差异表达和加权基因共表达网络方法分析数据。与骨骼肌收缩相关的蛋白质在老年骨骼肌中含量较低；抗阻训练未能使其恢复正常。抗阻训练后，老年女性股外侧肌线粒体生物发生蛋白的表达高于年轻女性，这与训练前的观察结果相反。年龄组之间有70种蛋白质存在差异表达。这些蛋白质在老年女性股外侧肌中的表达与较差的腿部力量/神经肌肉功能始终显著相关。相反，这些蛋白质在老年女性股外侧肌中的表达通常与较强的握力相关。本研究确定了年轻和老年骨骼肌对抗阻训练分子反应的重要差异。我们证明了它们与骨骼肌功能的密切关系。对抗阻训练无反应的蛋白质可能是改善肌肉减少症的靶点。我们描述了一种似乎具有肌肉特异性的“蛋白质组-功能”关系。未来的研究应进一步剖析这些复杂关系。
