Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
J Physiol. 2017 Oct 15;595(20):6391-6399. doi: 10.1113/JP274337. Epub 2017 Sep 24.
Skeletal muscle is important for overall functionality and health. Ageing is associated with an accumulation of damage to mitochondrial DNA and proteins. In particular, damage to mitochondrial proteins in skeletal muscle, which is a loss of mitochondrial proteostasis, contributes to tissue dysfunction and negatively impacts systemic health. Therefore, understanding the mechanisms underlying the regulation of mitochondrial proteostasis and how those mechanisms change with age is important for the development of interventions to promote healthy ageing. Herein, we examine how impairment in the selective degradation of damaged/dysfunctional mitochondria through mitophagy may play a central role in the loss of mitochondrial proteostasis in skeletal muscle ageing, as well as its broader implications for systemic health. Further, we explore how stimulating mitophagy through exercise may promote healthy ageing.
骨骼肌对于整体功能和健康至关重要。随着年龄的增长,线粒体 DNA 和蛋白质的损伤会逐渐积累。特别是骨骼肌中线粒体蛋白质的损伤,即线粒体蛋白稳态的丧失,会导致组织功能障碍,并对全身健康产生负面影响。因此,了解调控线粒体蛋白稳态的机制以及这些机制随年龄变化的方式,对于开发促进健康衰老的干预措施非常重要。本文中,我们探讨了通过线粒体自噬选择性降解受损/功能障碍线粒体的能力受损如何在骨骼肌衰老中线粒体蛋白稳态丧失中发挥核心作用,以及其对全身健康的更广泛影响。此外,我们还探讨了通过运动刺激线粒体自噬如何促进健康衰老。