Promotion of oxidative stress is associated with mitochondrial dysfunction and muscle atrophy in aging mice
Promotion of oxidative stress is associated with mitochondrial dysfunction and muscle atrophy in aging mice
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DOI：
10.1111/ggi.13818
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发表时间：
2019-11-22
影响因子：
3.3
通讯作者：
Daida, Hiroyuki
中科院分区：
文献类型：
--
作者：
Kadoguchi, Tomoyasu;Shimada, Kazunori;Daida, Hiroyuki
目的研究小鼠衰老过程中氧化应激、线粒体功能和肌肉萎缩的变化。方法采用6月龄、12月龄和24月龄（6 M、12 M和24 M）C57 BL/6 J小鼠。从下肢取出骨骼肌，用于定量实时聚合酶链反应、免疫印迹和组织学分析。结果与6 M小鼠相比，12 M和24 M小鼠的肌重和肌细胞横截面积均显著降低。氧化应激标志物烟酰胺腺嘌呤二核苷酸磷酸氧化酶2、烟酰胺腺嘌呤二核苷酸磷酸氧化酶4、线粒体4-羟基-2-壬烯醛和3-硝基酪氨酸的水平在24 M小鼠中显著高于6 M小鼠。此外，24 M小鼠的线粒体标志物、过氧化物酶体增殖物激活受体γ共激活因子1（PGC）-α、过氧化物酶体增殖物激活受体γ共激活因子-1 β、沉默调节蛋白-1、三磷酸腺苷合酶线粒体F1复合物α亚基1和线粒体细胞色素c氧化酶1水平较低。泛素-蛋白酶体途径基因muscle ring finger-1和atrogin-1在12 M和24 M小鼠中显著上调，蛋白质合成标志物（磷酸化Akt和-p70核糖体S6激酶）在24 M小鼠中显著低于6 M小鼠（均P < 0.05）。结论这些发现对肌少症和脆弱过程的机制具有重要意义。Geriatr Gerontol Int 2019;中心点中心点：中心点中心点-中心点中心点。
Aim We examined the changes in oxidative stress, mitochondrial function and muscle atrophy during aging in mice. Methods We used 6-, 12- and 24-month (6 M, 12 M and 24 M)-old C57BL/6J mice. Skeletal muscles were removed from the lower limb and used for quantitative real-time polymerase chain reaction, immunoblotting and histological analyses. Results The muscle weight and myocyte cross-sectional area were significantly decreased in the 12 M and 24 M mice compared with those of the 6 M mice. The levels of the oxidative stress markers, nicotinamide adenine dinucleotide phosphate oxidase 2, nicotinamide adenine dinucleotide phosphate oxidase 4, mitochondrial 4-hydroxy-2-nonenal and 3-nitrotyrosine, were significantly higher in the 24 M mice compared with those of the 6 M mice. Furthermore, the 24 M mice had lower levels of mitochondrial markers, peroxisome proliferator-activated receptor gamma coactivator 1 (PGC)-alpha, peroxisome proliferator-activated receptor gamma coactivator-1 beta, sirtuin-1, adenosine triphosphate synthase mitochondria F1 complex alpha subunit 1 and mitochondrial cytochrome c oxidase 1. The ubiquitin-proteasome pathway genes muscle ring finger-1 and atrogin-1 were significantly upregulated in the 12 M and 24 M mice, and protein synthesis markers (phosphorylated-Akt and -p70 ribosomal S6 kinase) were significantly lower in the 24 M mice compared with the 6 M mice (all P < 0.05). Conclusions These findings have important implications for the mechanisms that underlie sarcopenia and frailty processes. Geriatr Gerontol Int 2019; center dot center dot: center dot center dot-center dot center dot.