Transcriptomic meta-analysis of disuse muscle atrophy vs. resistance exercise-induced hypertrophy in young and older humans.
Transcriptomic meta-analysis of disuse muscle atrophy vs. resistance exercise-induced hypertrophy in young and older humans.
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年轻人和老年人废用性肌肉萎缩与抗阻运动引起的肥大的转录组荟萃分析。
DOI：
10.1002/jcsm.12706
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Etheridge T
中科院分区：
文献类型：
--
作者：
Deane CS;Willis CRG;Phillips BE;Atherton PJ;Harries LW;Ames RM;Szewczyk NJ;Etheridge T
骨骼肌萎缩表现在许多疾病中；然而，在萎缩条件之间的因果机制的相似/差异的程度尚不清楚。衰老和不使用是两种最普遍和最昂贵的萎缩性疾病，而抗阻运动训练（RET）是最有效的生活方式对策。我们采用基因水平和网络水平的荟萃分析来对比废用和RET，以及年轻和老年RET的转录组特征，以建立对高度社会经济相关性条件下肌肉萎缩的分子特征和治疗靶点的共识。整合基因水平和网络水平的荟萃分析对公开的微阵列数据集进行，这些数据集来自年轻（18-35岁）的股外侧肌，这些肌肉被废弃（单侧肢体固定或卧床休息）持续≥7天或RET持续≥3周，以及阻力训练的老年（≥60岁）肌肉。Disuse和RET主要表现出单独的转录反应，并且转录物在不同条件下的改变大多是单向的。然而，废用和RET直接诱导线粒体功能和翻译调节基因的表达谱倒置，其中COX4I1、ENDOG、GOT2、MRPL12和NDUFV2是线粒体网络改变的中心枢纽成分，ZMYND11是翻译调节改变的枢纽基因。大量基因（n = 140）在年轻肌肉中上调后RET，而在老年肌肉中没有类似的上调，年轻肌肉表现出更明显的细胞外基质（ECM）和免疫/炎症基因表达反应。年轻人和老年人的肌肉都表现出与相关的PWP1、PSMB1和RAF1枢纽基因相似的RET诱导的泛素化/RNA加工基因特征。尽管相对的基因图谱有限，但废用的转录特征并不是简单地与RET相反。因此，卸载的机制不能仅通过研究肌肉负荷而得出，这为理解为什么RET不能靶向废用的所有转录特征提供了分子基础。RET诱导的ECM机械转导和炎症谱的丧失也可能导致衰老肌肉对RET的适应不理想。废用和年龄依赖的候选分子进一步建立了理解和治疗废用/老化萎缩的框架。
Skeletal muscle atrophy manifests across numerous diseases; however, the extent of similarities/differences in causal mechanisms between atrophying conditions in unclear. Ageing and disuse represent two of the most prevalent and costly atrophic conditions, with resistance exercise training (RET) being the most effective lifestyle countermeasure. We employed gene‐level and network‐level meta‐analyses to contrast transcriptomic signatures of disuse and RET, plus young and older RET to establish a consensus on the molecular features of, and therapeutic targets against, muscle atrophy in conditions of high socio‐economic relevance. Integrated gene‐level and network‐level meta‐analysis was performed on publicly available microarray data sets generated from young (18–35 years) m. vastus lateralis muscle subjected to disuse (unilateral limb immobilization or bed rest) lasting ≥7 days or RET lasting ≥3 weeks, and resistance‐trained older (≥60 years) muscle. Disuse and RET displayed predominantly separate transcriptional responses, and transcripts altered across conditions were mostly unidirectional. However, disuse and RET induced directly inverted expression profiles for mitochondrial function and translation regulation genes, with COX4I1, ENDOG, GOT2, MRPL12, and NDUFV2, the central hub components of altered mitochondrial networks, and ZMYND11, a hub gene of altered translation regulation. A substantial number of genes (n = 140) up‐regulated post‐RET in younger muscle were not similarly up‐regulated in older muscle, with young muscle displaying a more pronounced extracellular matrix (ECM) and immune/inflammatory gene expression response. Both young and older muscle exhibited similar RET‐induced ubiquitination/RNA processing gene signatures with associated PWP1, PSMB1, and RAF1 hub genes. Despite limited opposing gene profiles, transcriptional signatures of disuse are not simply the converse of RET. Thus, the mechanisms of unloading cannot be derived from studying muscle loading alone and provides a molecular basis for understanding why RET fails to target all transcriptional features of disuse. Loss of RET‐induced ECM mechanotransduction and inflammatory profiles might also contribute to suboptimal ageing muscle adaptations to RET. Disuse and age‐dependent molecular candidates further establish a framework for understanding and treating disuse/ageing atrophy.
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DOI：
10.1113/jp272857
发表时间：
2016-12-15
期刊：
The Journal of physiology
影响因子：
--
作者：
Brook MS;Wilkinson DJ;Mitchell WK;Lund JN;Phillips BE;Szewczyk NJ;Greenhaff PL;Smith K;Atherton PJ
通讯作者：
Atherton PJ
影响因子：
4.6
作者：
Cahill KM;Huo Z;Tseng GC;Logan RW;Seney ML
通讯作者：
Seney ML
影响因子：
16.6
作者：
Agudelo, Leandro Z.;Ferreira, Duarte M. S.;Ruas, Jorge L.
通讯作者：
Ruas, Jorge L.
影响因子：
3
作者：
Damas, Felipe;Phillips, Stuart M.;Ugrinowitsch, Carlos
通讯作者：
Ugrinowitsch, Carlos
影响因子：
4.9
作者：
Bell RA;Al-Khalaf M;Megeney LA
通讯作者：
Megeney LA