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

描述(由申请人提供)：我提议的研究解决了我们在了解氧化应激如何导致肌肉损伤和功能衰老方面的具体空白。尽管有大量关于活性氧簇(ROS)的形成和氧化应激的潜在负面影响的信息，但很少有研究将代谢密集型运动与动物一生中肌肉损伤的积累、细胞保护机制的活动和肌肉表现联系起来。我将用蜜蜂--意大利蜜蜂来研究这些问题。蜜蜂是研究运动引起的氧化应激的极好生物，因为它们在飞行过程中产生的质量比代谢率是动物界测量到的最高的。此外，通过简单的蜂群操作，可以将蜜蜂的活动和年龄分开，这使得很少飞行的蜂群内的工蜂和每天飞行长达8公里、采集花蜜和花粉的同龄觅食者进行比较。我将通过测量日常觅食活动中高度新陈代谢的飞行肌肉和代谢活性较低的觅食者大脑组织发育和衰老过程中的氧化应激和抗氧化能力的标记物，来确定飞行肌肉中的氧化损伤和细胞保护机制的活性是否取决于活动，而不是年龄。然后，我将通过测量飞行表现、新陈代谢、氧化应激标记物、飞行肌肉质量以及线粒体有氧能力和ROS形成，来确定活动水平、线粒体ROS形成和氧化损伤是否与飞行肌肉组织的功能下降有关，而不是年龄。为了区分重复飞行活动和年龄对累积的肌肉损伤和衰老的影响，也将检查很少飞行的年龄匹配的蜂箱内的工蜂。蜜蜂的细胞保护机制与氧化损伤和肌肉功能相联系，将把由于重复活动和/或衰老引起的氧化损伤的细胞效应与肌肉衰老结合起来。这项研究将提供对人类肌肉衰老的洞察，以及与氧化应激相关的肌肉疾病的潜在机制。

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.