Ji Li Li, Kang Chounghun
Laboratory of Physiological Hygiene and Exercise Science, School of Kinesiology, University of Minnesota, Minneapolis, Minn., USA.
Gerontology. 2015;61(2):139-48. doi: 10.1159/000365947. Epub 2014 Dec 6.
Sarcopenia is age-associated deterioration of muscle mass and function caused by a wide scope of physiological and pathological changes ranging from hormonal disorders to loss of subcellular homeostasis. Recent research indicates that mitochondrial dysregulation with advanced age plays a central role in the development of sarcopenia due to the multifactorial functions of this organelle in energy supply, redox regulation, crosstalk with nuclear gene expression and apoptosis. In order to fulfill these roles, it is crucial that mitochondria maintain their own structural and functional integrity through biogenesis, antioxidant defense, fusion/fission dynamics and autophagy (mitophagy). Unfortunately, mitochondria undergo age-associated changes that compromise the above-mentioned properties that eventually contribute to the development of sarcopenia. The peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is involved in the transcriptional regulation of numerous nuclear and mitochondrial gene products participating in the cellular events that control muscle mass and function. Thus, it is not surprising that maintaining an optimal intracellular PGC-1α level and signaling activity is crucial in protecting the muscle from many degradative and destructive processes, such as proteolysis, oxidative damage, inflammation, uncontrolled autophagy and apoptosis. Physical exercise is a powerful stimulus to PGC-1α expression and signaling. Recent research indicates that PGC-1α-controlled mitochondrial biogenesis is not limited by old age per se and that elderly individuals can still benefit from increased muscular activity in terms of skeletal muscle health that ultimately contributes to quality of life in old age.
肌肉减少症是一种与年龄相关的肌肉质量和功能衰退，由从激素紊乱到亚细胞稳态丧失等广泛的生理和病理变化引起。最近的研究表明，随着年龄增长，线粒体功能失调在肌肉减少症的发生发展中起核心作用，因为该细胞器在能量供应、氧化还原调节、与核基因表达的相互作用以及细胞凋亡等多方面发挥作用。为了履行这些职责，线粒体通过生物发生、抗氧化防御、融合/裂变动态以及自噬（线粒体自噬）来维持自身结构和功能的完整性至关重要。不幸的是，线粒体发生与年龄相关的变化，损害了上述特性，最终导致肌肉减少症的发生。过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）参与众多参与控制肌肉质量和功能的细胞事件的核基因和线粒体基因产物的转录调控。因此，维持最佳的细胞内PGC-1α水平和信号活性对于保护肌肉免受许多降解和破坏过程（如蛋白水解、氧化损伤、炎症、不受控制的自噬和细胞凋亡）至关重要，这并不奇怪。体育锻炼是PGC-1α表达和信号传导的有力刺激因素。最近的研究表明，PGC-1α控制的线粒体生物发生本身并不受年龄增长的限制，老年人仍然可以从增加肌肉活动中受益，这对骨骼肌健康有益，并最终有助于提高老年生活质量。
