Rai Mamta, Demontis Fabio
Division of Developmental Biology, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105; email:
Annu Rev Physiol. 2016;78:85-107. doi: 10.1146/annurev-physiol-021115-105305. Epub 2015 Nov 2.
Homeostatic systems mount adaptive responses to meet the energy demands of the cell and to compensate for dysfunction in cellular compartments. Such surveillance systems are also active at the organismal level: Nutrient and stress sensing in one tissue can lead to changes in other tissues. Here, we review the emerging understanding of the role of skeletal muscle in regulating physiological homeostasis and disease progression in other tissues. Muscle-specific genetic interventions can induce systemic effects indirectly, via changes in the mass and metabolic demand of muscle, and directly, via the release of muscle-derived cytokines (myokines) and metabolites (myometabolites) in response to nutrients and stress. In turn, myokines and myometabolites signal to various target tissues in an autocrine, paracrine, and endocrine manner, thereby determining organismal resilience to aging, disease, and environmental challenges. We propose that tailoring muscle systemic signaling by modulating myokine and myometabolite levels may combat many degenerative diseases and delay aging.
稳态系统会产生适应性反应，以满足细胞的能量需求，并补偿细胞区室中的功能障碍。此类监测系统在机体水平也很活跃：一个组织中的营养和应激感知可导致其他组织发生变化。在此，我们综述了对骨骼肌在调节生理稳态和其他组织疾病进展中作用的新认识。肌肉特异性基因干预可通过肌肉质量和代谢需求的变化间接诱导全身效应，也可通过响应营养和应激释放肌肉衍生的细胞因子（肌动蛋白）和代谢产物（肌代谢产物）直接诱导全身效应。反过来，肌动蛋白和肌代谢产物以自分泌、旁分泌和内分泌方式向各种靶组织发出信号，从而决定机体对衰老、疾病和环境挑战的恢复力。我们提出，通过调节肌动蛋白和肌代谢产物水平来调整肌肉全身信号传导，可能有助于对抗许多退行性疾病并延缓衰老。
