Abstract：
Skeletal muscle wasting, whether related to physiological ageing, muscle disuse or to an underlying chronic disease, is a key determinant to quality of life and mortality. However, cellular basis responsible for increased catabolism in myocytes often remains unclear. Although myocytes represent the vast majority of skeletal muscle cellular population, they are surrounded by numerous cells with various functions. Animal models, mostly rodents, can help to decipher the mechanisms behind this highly dynamic process, by allowing access to every muscle as well as time-course studies. Satellite cells (SCs) play a crucial role in muscle regeneration, within a niche also composed of fibroblasts and vascular and immune cells. Their proliferation and differentiation is altered in several models of muscle wasting such as cancer, chronic kidney disease or chronic obstructive pulmonary disease (COPD). Fibro-adipogenic progenitor cells are also responsible for functional muscle growth and repair and are associated in disease to muscle fibrosis such as in chronic kidney disease. Other cells have recently proven to have direct myogenic potential, such as pericytes. Outside their role in angiogenesis, endothelial cells and pericytes also participate to healthy muscle homoeostasis by promoting SC pool maintenance (so-called myogenesis-angiogenesis coupling). Their role in chronic diseases muscle wasting has been less studied. Immune cells are pivotal for muscle repair after injury: Macrophages undergo a transition from the M1 to the M2 state along with the transition between the inflammatory and resolutive phase of muscle repair. T regulatory lymphocytes promote and regulate this transition and are also able to activate SC proliferation and differentiation. Neural cells such as terminal Schwann cells, motor neurons and kranocytes are notably implicated in age-related sarcopenia. Last, newly identified cells in skeletal muscle, such as telocytes or interstitial tenocytes could play a role in tissular homoeostasis. We also put a special focus on cellular alterations occurring in COPD, a chronic and highly prevalent respiratory disease mainly linked to tobacco smoke exposure, where muscle wasting is strongly associated with increased mortality, and discuss the pros and cons of animal models versus human studies in this context. Finally, we discuss resident cells metabolism and present future promising leads for research, including the use of muscle organoids.
摘要：
骨骼肌萎缩,是否与生理衰老有关，肌肉废用或潜在的慢性疾病，是生活质量和死亡率的关键决定因素。然而,导致肌细胞分解代谢增加的细胞基础通常尚不清楚。虽然肌细胞代表了绝大多数的骨骼肌细胞群，它们被许多具有各种功能的细胞包围。动物模型,主要是啮齿动物,可以帮助破译这个高度动态过程背后的机制，通过允许进入每一块肌肉以及时程研究。卫星细胞（SCs）在肌肉再生中起着至关重要的作用，在一个小生境内也由成纤维细胞和血管和免疫细胞组成。它们的增殖和分化在几种肌肉萎缩模型中发生了改变，例如癌症，慢性肾脏疾病或慢性阻塞性肺疾病（COPD）。纤维-脂肪生成祖细胞还负责功能性肌肉生长和修复,并且在疾病中与肌肉纤维化相关,例如在慢性肾病中。其他细胞最近被证明具有直接的生肌潜能，例如周细胞。除了它们在血管生成中的作用之外，内皮细胞和周细胞还通过促进SC池维持(所谓的肌生成-血管生成偶联)参与健康的肌肉稳态。它们在慢性疾病肌肉萎缩中的作用研究较少。免疫细胞对于损伤后的肌肉修复至关重要：巨噬细胞经历从M1状态到M2状态的转变，以及肌肉修复的炎症阶段和缓解阶段之间的转变。T调节淋巴细胞促进和调节这种转变,并且还能够激活SC增殖和分化。神经细胞，如终末施万细胞，运动神经元和红细胞与年龄相关的肌少症有显著的关系。最后,新发现的骨骼肌细胞，如端音细胞或间质肌腱细胞可能在组织稳态中发挥作用。我们还特别关注COPD中发生的细胞改变，一种主要与烟草烟雾接触有关的慢性和高度流行的呼吸道疾病，肌肉萎缩与死亡率增加密切相关，并在此背景下讨论动物模型与人体研究的利弊。最后,我们讨论了常驻细胞的新陈代谢，并提出了未来有希望的研究线索，包括使用肌肉类器官。
