Abstract

A decrease in muscle mass and its functionality (strength, endurance, and insulin sensitivity) is one of the integral signs of aging. One of the triggers of aging is an increase in the production of mitochondrial reactive oxygen species. Our study was the first to examine age-dependent changes in the production of mitochondrial reactive oxygen species related to a decrease in the proportion of mitochondria-associated hexokinase-2 in human skeletal muscle. For this purpose, a biopsy was taken from m. vastus lateralis in 10 young healthy volunteers and 70 patients (26-85 years old) with long-term primary arthrosis of the knee/hip joint. It turned out that aging (comparing different groups of patients), in contrast to inactivity/chronic inflammation (comparing young healthy people and young patients), causes a pronounced increase in peroxide production by isolated mitochondria. This correlated with the age-dependent distribution of hexokinase-2 between mitochondrial and cytosolic fractions, a decrease in the rate of coupled respiration of isolated mitochondria and respiration when stimulated with glucose (a hexokinase substrate). It is discussed that these changes may be caused by an age-dependent decrease in the content of cardiolipin, a potential regulator of the mitochondrial microcompartment containing hexokinase. The results obtained contribute to a deeper understanding of age-related pathogenetic processes in skeletal muscles and open prospects for the search for pharmacological/physiological approaches to the correction of these pathologies.

中文翻译：

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人类骨骼肌线粒体活性氧产生的年龄依赖性变化

摘要

肌肉质量及其功能（力量、耐力和胰岛素敏感性）的减少是衰老的重要迹象之一。衰老的诱因之一是线粒体活性氧产生的增加。我们的研究首次检验了线粒体活性氧产生的年龄依赖性变化，该变化与人类骨骼肌中线粒体相关己糖激酶-2 比例的下降有关。为此，对 m 进行了活组织检查。研究人员对 10 名年轻健康志愿者和 70 名患有长期原发性膝/髋关节关节炎的患者（26-85 岁）进行了股外侧肌的研究。事实证明，与不活动/慢性炎症（比较年轻健康人和年轻患者）相比，衰老（比较不同的患者群体）会导致孤立线粒体产生的过氧化物显着增加。这与线粒体和胞质部分之间的己糖激酶-2 的年龄依赖性分布、分离线粒体的耦合呼吸速率和用葡萄糖（己糖激酶底物）刺激时的呼吸速率降低相关。据讨论，这些变化可能是由于心磷脂含量随年龄的减少而引起的，心磷脂是含有己糖激酶的线粒体微区室的潜在调节剂。获得的结果有助于更深入地了解骨骼肌中与年龄相关的发病过程，并为寻找纠正这些病理的药理学/生理学方法开辟了前景。