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微小RNA:肌肉减少症潜在病理生理学的调节因子?

microRNAs: Modulators of the underlying pathophysiology of sarcopenia?

作者信息

Brown David M, Goljanek-Whysall Katarzyna

机构信息

Medical Research Council-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

出版信息

Ageing Res Rev. 2015 Nov;24(Pt B):263-73. doi: 10.1016/j.arr.2015.08.007. Epub 2015 Sep 2.

Abstract

Skeletal muscle homeostasis depends on an intricate balance between muscle hypertrophy, atrophy and regeneration. As we age, maintenance of muscle homeostasis is perturbed, resulting in a loss of muscle mass and function, termed sarcopenia. Individuals with sarcopenia exhibit impaired balance, increased falls (leading to subsequent injury) and an overall decline in quality of life. The mechanisms mediating sarcopenia are still not fully understood but clarity in our understanding of the precise pathophysiological changes occurring during skeletal muscle ageing has improved dramatically. Advances in transcriptomics has highlighted significant deregulation in skeletal muscle gene expression with ageing, suggesting epigenetic alterations may play a crucial and potentially causative role in the skeletal muscle ageing process. microRNAs (miRNAs, miRs), novel regulators of gene expression, can modulate many processes in skeletal muscle, including myogenesis, tissue regeneration and cellular programming. Expression of numerous evolutionary conserved miRNAs is disrupted in skeletal muscle with age. Given that a single miRNA can simultaneously affect the functionality of multiple signaling pathways, miRNAs are potent modulators of pathophysiological changes. miRNA-based interventions provide a promising new therapeutic strategy against alterations in muscle homeostasis. The aim of this review is two-fold; firstly to outline the latest understanding of the pathophysiological alterations impacting the deregulation of skeletal muscle mass and function with ageing, and secondly, to highlight the mounting evidence for a role of miRNAs in modulating muscle mass, and the need to explore their specific role in sarcopenia.

摘要

骨骼肌稳态取决于肌肉肥大、萎缩和再生之间的复杂平衡。随着年龄的增长,肌肉稳态的维持受到干扰,导致肌肉质量和功能丧失,即肌肉减少症。患有肌肉减少症的个体表现出平衡受损、跌倒增加(导致随后的损伤)以及生活质量整体下降。介导肌肉减少症的机制仍未完全了解,但我们对骨骼肌衰老过程中发生的精确病理生理变化的理解有了显著提高。转录组学的进展突出了随着年龄增长骨骼肌基因表达的显著失调,表明表观遗传改变可能在骨骼肌衰老过程中起关键且潜在的致病作用。微小RNA(miRNA,miRs)是基因表达的新型调节因子,可调节骨骼肌中的许多过程,包括肌发生、组织再生和细胞编程。随着年龄的增长,许多进化保守的miRNA在骨骼肌中的表达会受到破坏。鉴于单个miRNA可以同时影响多个信号通路的功能,miRNA是病理生理变化的有效调节因子。基于miRNA的干预为对抗肌肉稳态改变提供了一种有前景的新治疗策略。本综述的目的有两个;首先概述对影响骨骼肌质量和功能随年龄失调的病理生理改变的最新理解,其次强调越来越多的证据表明miRNA在调节肌肉质量中的作用,以及探索它们在肌肉减少症中的具体作用的必要性。

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