Hesketh Stuart J
University of Central Lancashire, School of Medicine, Preston, UK.
Sports Med Health Sci. 2024 Jan 28;6(1):1-15. doi: 10.1016/j.smhs.2024.01.006. eCollection 2024 Mar.
Muscle atrophy exacerbates disease outcomes and increases mortality, whereas the preservation of skeletal muscle mass and function play pivotal roles in ensuring long-term health and overall quality-of-life. Muscle atrophy represents a significant clinical challenge, involving the continued loss of muscle mass and strength, which frequently accompany the development of numerous types of cancer. Cancer cachexia is a highly prevalent multifactorial syndrome, and although cachexia is one of the main causes of cancer-related deaths, there are still no approved management strategies for the disease. The etiology of this condition is based on the upregulation of systemic inflammation factors and catabolic stimuli, resulting in the inhibition of protein synthesis and enhancement of protein degradation. Numerous necessary cellular processes are disrupted by cachectic pathology, which mediate intracellular signalling pathways resulting in the net loss of muscle and organelles. However, the exact underpinning molecular mechanisms of how these changes are orchestrated are incompletely understood. Much work is still required, but structured exercise has the capacity to counteract numerous detrimental effects linked to cancer cachexia. Primarily through the stimulation of muscle protein synthesis, enhancement of mitochondrial function, and the release of myokines. As a result, muscle mass and strength increase, leading to improved mobility, and quality-of-life. This review summarises existing knowledge of the complex molecular networks that regulate cancer cachexia and exercise, highlighting the molecular interplay between the two for potential therapeutic intervention. Finally, the utility of mass spectrometry-based proteomics is considered as a way of establishing early diagnostic biomarkers of cachectic patients.
肌肉萎缩会加剧疾病后果并增加死亡率,而保持骨骼肌质量和功能对于确保长期健康和总体生活质量起着关键作用。肌肉萎缩是一项重大的临床挑战,涉及肌肉质量和力量的持续丧失,这常常伴随多种癌症的发展。癌症恶病质是一种高度普遍的多因素综合征,尽管恶病质是癌症相关死亡的主要原因之一,但针对该疾病仍没有获批的管理策略。这种情况的病因基于全身炎症因子和分解代谢刺激的上调,导致蛋白质合成受到抑制以及蛋白质降解增强。恶病质病理破坏了许多必要的细胞过程,这些过程介导细胞内信号通路,导致肌肉和细胞器的净损失。然而,对于这些变化是如何协调的的确切分子机制仍不完全清楚。仍需要做大量工作,但有组织的运动有能力抵消与癌症恶病质相关的许多有害影响。主要是通过刺激肌肉蛋白质合成、增强线粒体功能以及释放肌动蛋白。结果,肌肉质量和力量增加,从而改善活动能力和生活质量。本综述总结了调节癌症恶病质和运动的复杂分子网络的现有知识,强调了两者之间的分子相互作用以进行潜在的治疗干预。最后,基于质谱的蛋白质组学的实用性被视为建立恶病质患者早期诊断生物标志物的一种方法。