MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
Sci Rep. 2019 Oct 8;9(1):14461. doi: 10.1038/s41598-019-51035-w.
To determine the role of denervation and motor unit turnover in the age-related increase in skeletal muscle oxidative stress, the hydrogen peroxide (HO) specific, genetically-encoded, fluorescent cyto-HyPer2 probe was expressed in mouse anterior tibialis (AT) muscle and compared with ex vivo measurements of mitochondrial oxidant generation. Crush of the peroneal nerve induced increased mitochondrial peroxide generation, measured in permeabilised AT fibers ex vivo and intra vital confocal microscopy of cyto-HyPer2 fluorescence showed increased cytosolic HO in a sub-set (~24%) of individual fibers associated with onset of fiber atrophy. In comparison, mitochondrial peroxide generation was also increased in resting muscle from old (26 month) mice compared with adult (6-8 month) mice, but no age effect on fiber cytosolic HO in vivo was seen. Thus ageing is associated with an increased ability of muscle fibers to maintain cytosolic redox homeostasis in the presence of denervation-induced increase in mitochondrial peroxide generation.
为了确定去神经支配和运动单位更替在骨骼肌氧化应激与年龄相关增加中的作用，在小鼠前胫骨（AT）肌肉中表达了过氧化氢（HO）特异性、基因编码的荧光细胞-Hyper2 探针，并与线粒体氧化剂生成的离体测量进行了比较。腓总神经压榨导致线粒体过氧化物生成增加，在体外渗透 AT 纤维中测量，并在细胞内共聚焦显微镜下观察细胞-Hyper2 荧光显示，与纤维萎缩开始相关的个别纤维亚群（约 24%）中细胞浆中的 HO 增加。相比之下，与成年（6-8 个月）小鼠相比，老年（26 个月）小鼠的静息肌肉中的线粒体过氧化物生成也增加，但在体内未观察到纤维细胞浆 HO 随年龄的变化。因此，衰老与在去神经支配诱导的线粒体过氧化物生成增加的情况下，肌肉纤维维持细胞浆氧化还原稳态的能力增加有关。
