Soriano-Arroquia Ana, House Louise, Tregilgas Luke, Canty-Laird Elizabeth, Goljanek-Whysall Katarzyna
MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Apex Building, West Derby Road, Liverpool, L8 7TX, UK.
Biogerontology. 2016 Jun;17(3):641-54. doi: 10.1007/s10522-016-9638-8. Epub 2016 Feb 27.
A common characteristic of ageing is disrupted homeostasis between growth and atrophy of skeletal muscle resulting in loss of muscle mass and function, which is associated with sarcopenia. Sarcopenia is related to impaired balance, increased falls and decline in quality of life of older people. Ageing-related transcriptome and proteome changes in skeletal muscle have been characterised, however the molecular mechanisms underlying sarcopenia are still not fully understood. microRNAs are novel regulators of gene expression known to modulate skeletal muscle development and homeostasis. Expression of numerous microRNAs is disrupted in skeletal muscle with age however, the functional consequences of this are not yet understood. Given that a single microRNA can simultaneously affect multiple signalling pathways, microRNAs are potent modulators of pathophysiological changes occurring during ageing. Here we use microRNA and transcript expression profiling together with microRNA functional assays to show that disrupted microRNA:target interactions play an important role in maintaining muscle homeostasis. We identified miR-181a as a regulator of the sirtuin1 (Sirt1) gene expression in skeletal muscle and show that the expression of miR-181a and its target gene is disrupted in skeletal muscle from old mice. Moreover, we show that miR-181a:Sirt1 interactions regulate myotube size. Our results demonstrate that disrupted microRNA:target interactions are likely related to the pathophysiological changes occurring in skeletal muscle during ageing.
衰老的一个共同特征是骨骼肌生长与萎缩之间的稳态被破坏，导致肌肉质量和功能丧失，这与肌肉减少症相关。肌肉减少症与老年人平衡能力受损、跌倒增加及生活质量下降有关。骨骼肌中与衰老相关的转录组和蛋白质组变化已得到表征，然而，肌肉减少症的分子机制仍未完全明确。微小RNA是已知可调节骨骼肌发育和稳态的新型基因表达调节因子。随着年龄增长，骨骼肌中许多微小RNA的表达受到干扰，但其功能后果尚不清楚。鉴于单个微小RNA可同时影响多个信号通路，微小RNA是衰老过程中发生的病理生理变化的有效调节因子。在此，我们使用微小RNA和转录本表达谱分析以及微小RNA功能测定，以表明被破坏的微小RNA：靶标相互作用在维持肌肉稳态中起重要作用。我们鉴定出miR-181a是骨骼肌中沉默调节蛋白1（Sirt1）基因表达的调节因子，并表明miR-181a及其靶基因的表达在老年小鼠的骨骼肌中受到干扰。此外，我们表明miR-181a：Sirt1相互作用调节肌管大小。我们的结果表明，被破坏的微小RNA：靶标相互作用可能与衰老过程中骨骼肌发生的病理生理变化有关。
