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性衰老的理解中的具体空白。尽管关于活性氧（ROS）的形成和氧化应激的潜在负面影响有相当多的信息，但很少有研究将代谢强度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（Apis mellifera）来检验这些问题。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特定代谢率在动物王国中是最高的。此外，通过简单的蜂群操作，可以将蜜蜂的活动和年龄区分开来，从而可以比较蜂群内很少飞行的工蜂和每天飞行8公里采集花蜜和花粉的同龄觅食者。我将通过测量觅食者在高代谢飞行肌肉和低代谢大脑组织的日常觅食活动中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，通过测量飞行性能、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形成在觅食者一生中的几个阶段。为了分离重复飞行活动和年龄对累积肌肉损伤和衰老的影响，也将对年龄匹配的、很少飞行的蜂巢内工蜂进行研究。将蜜蜂细胞保护与氧化损伤和肌肉表现联系起来的机制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。这项研究将为人类肌肉衰老和与氧化应激相关的肌肉疾病的机制提供见解。