The effect of oxidative stress on muscle damage and functional senesence.

描述（由申请人提供）：我提出的研究解决了我们对氧化应激如何导致肌肉损伤和功能性衰老的理解中的具体差距。虽然有相当多的信息是关于活性氧（ROS）的形成和氧化应激的潜在负面影响，很少有研究联系代谢密集型运动的积累肌肉损伤，细胞保护机制的活动，肌肉性能在动物的寿命。我将用蜜蜂（Apis mellifera）来检验这些问题。蜜蜂是研究运动诱导的氧化应激的极好生物体，因为它们在飞行期间产生动物王国中测量的最高质量特定代谢率。此外，可以通过简单的群体操作来分离蜜蜂的活动和年龄，从而允许在很少飞行的群体内工蜂与每天飞行高达8公里同时收集花蜜和花粉的同龄觅食蜂之间进行比较。我将确定是否氧化损伤和细胞保护机制的活动在飞行肌肉是依赖于活动，而不是年龄，通过测量标记的氧化应激和抗氧化能力在日常觅食活动中的高代谢的飞行肌肉和代谢活跃的大脑组织觅食，因为他们的发展，然后衰老。然后，我将确定活动水平，线粒体ROS形成和氧化损伤，而不是年龄，与飞行肌肉组织的功能下降有关，通过测量飞行性能，代谢，氧化应激标志物，飞行肌肉质量，线粒体有氧能力和ROS形成在整个觅食者的生活中的几个点。为了分离重复飞行活动和年龄对累积的肌肉损伤和衰老的影响，还将检查年龄匹配的、很少飞行的蜂巢内工蜂。将蜜蜂的细胞保护机制与氧化损伤和肌肉性能联系起来，将整合由于重复活动和/或衰老引起的氧化损伤的细胞效应与肌肉衰老。这项研究将深入了解人类肌肉老化以及与氧化应激相关的肌肉疾病的机制。

DESCRIPTION (provided by applicant): My proposed research addresses specific gaps in our understanding of how oxidative stress contributes to muscle damage and functional senescence. Although considerable information is available regarding the formation of reactive oxygen species (ROS) and potential negative effects of oxidative stress, few studies link metabolically-intensive exercise to the accumulation of muscle damage, activity of cellular protective mechanisms, and muscle performance over the course of an animal's life span. I will examine these questions using the honey bee, Apis mellifera. Honey bees are extremely good organisms for studies of exercise induced oxidative stress because they produce the highest mass-specific metabolic rate measured in the animal kingdom during flight. In addition, activity and age can be separated in honey bees through a simple colony manipulation, allowing comparisons between in-colony workers, that rarely fly, and same- aged foragers that fly up to 8 km a day while gathering nectar and pollen. I will determine if oxidative damage and the activity of cellular protective mechanisms in flight muscle are dependant on activity rather than age by measuring markers of oxidative stress and antioxidant capacity during daily foraging activity in the highly metabolic flight muscles and less metabolically active brain tissue of foragers as they develop and then senesce. I will then determine if activity level, mitochondrial ROS formation, and oxidative damage, rather than age, are linked to functional declines in flight muscle tissue by measuring flight performance, metabolism, markers of oxidative stress, flight muscle mass, and mitochondrial aerobic capacity and ROS formation at several points throughout a forager's life. To separate the affect of repeated flight activity and age on accrued muscle damage and senescence, aged-matched, in-hive worker bees that rarely fly will also be examined. Linking mechanisms of cellular protection with oxidative damage and muscle performance in honey bees will integrate the cellular effects of oxidative damage due to repeated activity and/or aging with muscle senescence. This research will provide insight into muscle aging in humans and mechanisms underlying muscular diseases associated with oxidative stress.