Ageing in relation to skeletal muscle dysfunction: redox homoeostasis to regulation of gene expression.
Ageing in relation to skeletal muscle dysfunction: redox homoeostasis to regulation of gene expression.
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DOI：
10.1007/s00335-016-9643-x
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
McDonagh B
中科院分区：
文献类型：
--
作者：
Goljanek-Whysall K;Iwanejko LA;Vasilaki A;Pekovic-Vaughan V;McDonagh B
衰老与骨骼肌质量、质量和功能的逐渐丧失有关--骨质疏松症，与老年人的独立性和生活质量降低有关。更好地了解这一过程背后的遗传和表观遗传机制将有助于开发治疗干预措施，以防止、减缓或扭转与衰老相关的肌肉萎缩。目前，运动是唯一已知的延缓石棺减少进展的有效干预措施。运动后肌肉纤维中发生的细胞反应为调节肌肉内稳态的分子机制提供了有价值的线索，并可能导致骨骼肌减少症的进展。氧化还原信号是肌肉收缩时内源性产生ROS/RNS的结果，已被认为是运动适应性反应的关键调节因素，突显了氧化还原环境是在衰老过程中维持肌肉内稳态的潜在核心治疗方法。更新颖和有吸引力的候选包括对microRNA表达的操纵。MicroRNAs是参与控制健康和疾病相关生物过程的有效基因调节器，其治疗潜力已在各种疾病的背景下进行研究，包括与衰老相关的肌肉萎缩。最后，我们讨论了生物钟对骨骼肌基因表达调控的影响，以及周围肌钟的中断是否会影响骨骼肌肌纤维减少和运动反应的改变。干预措施包括改变氧化还原信号随着年龄的变化，并纳入遗传机制，如基于昼夜节律和基于microRNA的基因调控，可能提供潜在的有效治疗与年龄相关的石棺减少。
Ageing is associated with a progressive loss of skeletal muscle mass, quality and function—sarcopenia, associated with reduced independence and quality of life in older generations. A better understanding of the mechanisms, both genetic and epigenetic, underlying this process would help develop therapeutic interventions to prevent, slow down or reverse muscle wasting associated with ageing. Currently, exercise is the only known effective intervention to delay the progression of sarcopenia. The cellular responses that occur in muscle fibres following exercise provide valuable clues to the molecular mechanisms regulating muscle homoeostasis and potentially the progression of sarcopenia. Redox signalling, as a result of endogenous generation of ROS/RNS in response to muscle contractions, has been identified as a crucial regulator for the adaptive responses to exercise, highlighting the redox environment as a potentially core therapeutic approach to maintain muscle homoeostasis during ageing. Further novel and attractive candidates include the manipulation of microRNA expression. MicroRNAs are potent gene regulators involved in the control of healthy and disease-associated biological processes and their therapeutic potential has been researched in the context of various disorders, including ageing-associated muscle wasting. Finally, we discuss the impact of the circadian clock on the regulation of gene expression in skeletal muscle and whether disruption of the peripheral muscle clock affects sarcopenia and altered responses to exercise. Interventions that include modifying altered redox signalling with age and incorporating genetic mechanisms such as circadian- and microRNA-based gene regulation, may offer potential effective treatments against age-associated sarcopenia.