ROS STRESS AND DAMAGE TO OLD MUSCLE AFTER CONTRACTION

肌肉萎缩和无力通过福尔斯跌倒造成无数的伤害，并损害生活质量，但肌肉萎缩和无力的原因尚不清楚。目的是确定有氧收缩方案对8月龄（年轻/成年）和28月龄（老年）小鼠骨骼肌中活性氧（ROS）产生、ROS诱导的损伤和热休克蛋白（HSPs）适应性的影响。将在野生型（WT）小鼠和具有缺陷或增强的线粒体和胞质抗氧化系统的基因敲除和转基因小鼠之间进行比较。 在需氧生物中，ROS不断产生，其中85%在线粒体中产生，其余来自线粒体外来源。线粒体和细胞质中的抗氧化系统是复杂的、多样的和适应性强的。因此，特别是在具有完整或增强的抗氧化系统的年轻健康动物中，即使在要求严格的收缩方案的增加的ROS产生的情况下，超氧阴离子的产生ROS应激，但没有ROS损伤。相反，老年动物或抗氧化系统受损的动物，ROS应激有可能在休息或收缩时产生损伤。工作假设是年龄（年轻/成年或老年），代谢状态（静止或收缩）和抗氧化状态（完整，线粒体或胞质敲除，或通过遗传修饰的调节增强）将对ROS应激的大小以及ROS损伤的严重性和持久性产生相互作用。为了严格检验工作假设，将比较具有完整抗氧化系统或在线粒体（SodTg+/0、Sod 2 +/-和Sod 2D 3-/-小鼠）或胞质溶胶（Sod 1 +/-和Sod 1-/-小鼠）中具有增强或受损的抗氧化系统的年轻/成年和老年小鼠的骨骼肌，同时静止或遵循有氧收缩的要求方案。五个具体的假设将进行测试，这将提供主要的新的见解，ROS压力和抗氧化状态的条件下，导致严重和永久性损伤骨骼肌纤维后，一个苛刻的有氧收缩协议。非常重要的假设是，只有抗氧化系统完整的小鼠才会出现条件反射。

Atrophy and weakness cause countless injuries through falls and impair the quality of life, yet the cause of muscle atrophy and weakness is unknown. The purpose is to determine the effect of a aerobic contraction protocol on the generation of reactive oxygen (ROS), ROS-induced damage and the adaptations of heat shock proteins (HSPs) in skeletal muscles of 8-month old (young/adult) and 28-month-old (old) mice. Comparisons will be made among wild type (WT) mice and knockout and transgenic mice with deficient or enhanced mitochondrial and cytosolic antioxidant systems. In aerobic organisms, ROS are generated constantly with 85% generated in the mitochondria and the remainder from extra mitochondrial sources. The antioxidant systems are complex, diverse and adaptable in both the mitochondria and the cytosol. Consequently, particularly in young healthy animals with intact or enhanced antioxidant systems, even with the increased ROS generation of a demanding contraction protocol, the generation of superoxide anion produces an ROS stress, but no ROS damage. In contrast, old animals, or animals with impaired antioxidant systems, ROS stress has the potential to produce damage at rest or with contraction protocols. The working hypothesis is that age (young/adult or old), metabolic status (quiescent or contracting), and antioxidant status (intact, mitochondrial or cytosolic knock out, or enhanced through conditioning of genetic modification), will interact on the magnitude of the ROS stress and the severity and permanence of the ROS damage. To test the working hypothesis rigorously, skeletal muscles of young/adult and old mice with intact antioxidant systems, or with antioxidant systems enhanced or impaired in either the mitochondria (SodTg+/0, Sod2+/- and Sod2D3-/- mice) or cytosol (Sod1+/- and Sod1-/- mice) will be compared while quiescent or following a demanding protocol of aerobic contractions. Five specific hypotheses will be tested that will provide major new insights as to the conditions of ROS stress and antioxidant status that lead to severe and permanent damage to skeletal muscle fibers following a demanding aerobic contraction protocol. Of great importance is the hypothesis that only mice with intact antioxidant systems will condition.