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

氧化应激对肌肉损伤和功能衰老的影响。

• 批准号: 7497989
• 负责人: Jason Williams
• 金额: $ 4.96万
• 依托单位: UNIVERSITY OF NEVADA LAS VEGAS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-10 至 2009-04-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497989
• 关键词: Address; Aerobic; Affect; Age; Aging; Animals; Antioxidants; Apis; Bees; Daily; Exercise; Honey; Human; Life; Link; Longevity; Measures; Metabolic; Metabolism; Mitochondria; Muscle; Myopathy; Organism; Oxidative Stress; Performance; Pollen; Rate; Reactive Oxygen Species; Research; Stress; Time; Tissues; Urticaria; aged; brain tissue; day; fly; functional decline; insight; relating to nervous system; senescence

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.

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衰老的理解中的具体差距。尽管关于活性氧（ROS）的形成和氧化应激的潜在负面影响有大量信息，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性能联系起来。我将使用蜜蜂（Apis mellifera）来研究这些问题。蜜蜂是研究运动引起的氧化应激的极好的生物体，因为它们在飞行过程中产生动物界中最高的质量特定代谢率。此外，通过简单的蜂群操作，可以区分蜜蜂的活动和年龄，从而可以对很少飞行的蜂群内工蜂和每天飞行长达 8 公里收集花蜜和花粉的同龄采集工进行比较。我将通过测量日常觅食活动期间高代谢飞行肌和代谢不活跃的觅食者脑组织在发育和衰老过程中的氧化应激和抗氧化能力标志物，来确定飞行肌中的氧化损伤和细胞保护机制的活性是否依赖于活动而不是年龄。然后，我将通过测量觅食者一生中几个时间点的飞行表现、新陈代谢、氧化应激标志物、飞行肌肉质量、线粒体有氧能力和ROS形成，确定活动水平、线粒体ROS形成和氧化损伤（而不是年龄）是否与飞行肌肉组织的功能下降有关。为了区分重复飞行活动和年龄对肌肉损伤和衰老的影响，还将对年龄匹配、很少飞行的蜂巢内工蜂进行检查。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/或衰老与肌肉衰老而导致的氧化损伤的细胞效应。这项研究将深入了解人类肌肉衰老以及与氧化应激相关的肌肉疾病的机制。