MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
Institute of Inflammation and Ageing, MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, Queen Elizabeth Hospital, The University of Birmingham, Birmingham, UK.
Geroscience. 2021 Feb;43(1):85-110. doi: 10.1007/s11357-021-00322-4. Epub 2021 Feb 2.
Sarcopenia, broadly defined as the age-related decline in skeletal muscle mass, quality, and function, is associated with chronic low-grade inflammation and an increased likelihood of adverse health outcomes. The regulation of skeletal muscle mass with ageing is complex and necessitates a delicate balance between muscle protein synthesis and degradation. The secretion and transfer of cytokines, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), both discretely and within extracellular vesicles, have emerged as important communication channels between tissues. Some of these factors have been implicated in regulating skeletal muscle mass, function, and pathologies and may be perturbed by excessive adiposity. Indeed, adipose tissue participates in a broad spectrum of inter-organ communication and obesity promotes the accumulation of macrophages, cellular senescence, and the production and secretion of pro-inflammatory factors. Pertinently, age-related sarcopenia has been reported to be more prevalent in obesity; however, such effects are confounded by comorbidities and physical activity level. In this review, we provide evidence that adiposity may exacerbate age-related sarcopenia and outline some emerging concepts of adipose-skeletal muscle communication including the secretion and processing of novel myokines and adipokines and the role of extracellular vesicles in mediating inter-tissue cross talk via lncRNAs and miRNAs in the context of sarcopenia, ageing, and obesity. Further research using advances in proteomics, transcriptomics, and techniques to investigate extracellular vesicles, with an emphasis on translational, longitudinal human studies, is required to better understand the physiological significance of these factors, the impact of obesity upon them, and their potential as therapeutic targets in combating muscle wasting.
肌肉减少症广义上被定义为与年龄相关的骨骼肌质量、质量和功能下降,与慢性低度炎症和不良健康结果的可能性增加有关。随着年龄的增长,骨骼肌质量的调节是复杂的,需要在肌肉蛋白合成和降解之间保持微妙的平衡。细胞因子、长链非编码 RNA(lncRNA)和 microRNAs(miRNA)的分泌和转移,无论是离散的还是在细胞外囊泡内,都已经成为组织间重要的通讯渠道。其中一些因素被认为参与调节骨骼肌质量、功能和病理,并且可能会被过度肥胖所干扰。事实上,脂肪组织参与广泛的器官间通讯,肥胖会促进巨噬细胞的积累、细胞衰老以及促炎因子的产生和分泌。值得注意的是,与年龄相关的肌肉减少症在肥胖中更为普遍;然而,这些影响受到合并症和身体活动水平的影响。在这篇综述中,我们提供了证据表明肥胖可能会加重与年龄相关的肌肉减少症,并概述了一些新兴的脂肪-骨骼肌通讯概念,包括新型肌因子和脂肪因子的分泌和加工,以及细胞外囊泡在介导肌肉减少症、衰老和肥胖背景下组织间交叉对话中的 lncRNA 和 miRNA 的作用。需要使用蛋白质组学、转录组学和研究细胞外囊泡的技术的进展进行进一步研究,重点是转化、纵向的人类研究,以更好地理解这些因素的生理意义、肥胖对它们的影响以及它们作为对抗肌肉消耗的治疗靶点的潜力。