Expression of protocadherin gamma in skeletal muscle tissue is associated with age and muscle weakness. Expression of protocadherin gamma in skeletal muscle tissue is associated with age and muscle weakness

The skeletal muscle system plays an important role in the independence of older adults. In this study we examine differences in the skeletal muscle transcriptome between healthy young and older subjects and (pre‐)frail older adults. Additionally, we examine the effect of resistance‐type exercise training on the muscle transcriptome in healthy older subjects and (pre‐)frail older adults. Baseline transcriptome profiles were measured in muscle biopsies collected from 53 young, 73 healthy older subjects, and 61 frail older subjects. Follow‐up samples from these frail older subjects (31 samples) and healthy older subjects (41 samples) were collected after 6 months of progressive resistance‐type exercise training. Frail older subjects trained twice per week and the healthy older subjects trained three times per week. At baseline genes related to mitochondrial function and energy metabolism were differentially expressed between older and young subjects, as well as between healthy and frail older subjects. Three hundred seven genes were differentially expressed after training in both groups. Training affected expression levels of genes related to extracellular matrix, glucose metabolism, and vascularization. Expression of genes that were modulated by exercise training was indicative of muscle strength at baseline. Genes that strongly correlated with strength belonged to the protocadherin gamma gene cluster (r = −0.73). Our data suggest significant remaining plasticity of ageing skeletal muscle to adapt to resistance‐type exercise training. Some age‐related changes in skeletal muscle gene expression appear to be partially reversed by prolonged resistance‐type exercise training. The protocadherin gamma gene cluster may be related to muscle denervation and re‐innervation in ageing muscle. Overall design: Gene expression was profiled in human skeletal muscle (vastus lateralis) in young and older subjects. Older subjects (frail and healthy) participated in progressive resistance-type exercise training.

骨骼肌系统对老年人的日常独立生活能力具有关键作用。本研究旨在探究健康青年与老年受试者，以及衰弱前期（pre-frail）和衰弱老年受试者之间的骨骼肌转录组差异。此外，本研究还考察了抗阻型运动训练对健康老年受试者及衰弱前期、衰弱老年受试者肌肉转录组的调控效应。本研究共采集53名青年、73名健康老年受试者以及61名衰弱老年受试者的肌肉活检样本，以检测其基线转录组特征。在接受6个月的渐进式抗阻运动训练后，分别采集两类老年受试者的随访样本：其中衰弱老年受试者31份，健康老年受试者41份。衰弱老年受试者的训练频率为每周2次，健康老年受试者则为每周3次。基线分析显示，老年与青年受试者之间、健康老年与衰弱老年受试者之间，均存在与线粒体功能及能量代谢相关的差异表达基因。两组受试者训练后共筛选出307个差异表达基因。运动训练可调控与细胞外基质、糖代谢及血管生成相关的基因表达水平。运动训练所调控的基因表达特征，可反映受试者基线时的肌肉力量水平。与肌肉力量强相关的基因属于原钙粘蛋白γ基因簇（protocadherin gamma gene cluster），二者相关系数r=-0.73。本研究数据表明，衰老骨骼肌对渐进式抗阻运动训练的适应性仍具有显著可塑性。部分与衰老相关的骨骼肌基因表达改变，可通过长期抗阻运动训练得到部分逆转。原钙粘蛋白γ基因簇可能与衰老肌肉的神经支配丧失及再支配过程密切相关。研究整体设计：对青年及老年受试者的人体骨骼肌（股外侧肌，vastus lateralis）开展基因表达谱分析。老年受试者（涵盖健康与衰弱群体）均参与了渐进式抗阻运动训练。