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。

基本信息

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
项目类别：
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

项目摘要

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有助于肌肉损害和功能衰老的理解时的特定差距。尽管有大量有关活性氧（ROS）形成的信息（ROS）和氧化应激的潜在负面影响，但很少有研究将代谢强度的运动与肌肉损伤的积累，细胞保护机制的活性以及在动物寿命过程中的肌肉表现联系起来。我将使用Honey Bee，Apis Mellifera研究这些问题。蜜蜂是非常好的生物，用于研究运动诱导的氧化应激，因为它们在飞行过程中产生了在动物界中测得的最高质量特异性代谢率。此外，可以通过简单的菌落操纵在蜜蜂中分离活动和年龄，从而可以在殖民地工人之间进行比较，这些工人很少飞行，并且在收集花蜜和花粉的同时每天飞行到每天高达8 km。我将确定飞行肌肉中细胞保护机制的活性是否取决于活性而不是年龄，通过测量在高度代谢飞行肌肉中的氧化应激和抗氧化能力的标志物以及觅食者发育和参议员的觅食者的较低代谢活性脑组织中。然后，我将确定活动水平，线粒体ROS的形成和氧化损伤，而不是年龄是否通过测量飞行性能，代谢，氧化应激，氧化肌肉质量和线粒体有氧运动能力和ROS在多个生命中的多个点形成，与飞行肌肉组织的功能下降有关。为了区分重复的飞行活动和年龄对应计肌肉损害和衰老的影响，还将检查很少有飞翔的老年人匹配的内蜜蜂。将细胞保护的机制与蜂蜜蜜蜂中的氧化损伤和肌肉性能联系起来将整合由于反复活性和/或衰老而随着肌肉衰老而引起的氧化损伤的细胞效应。这项研究将洞悉人类的肌肉衰老以及与氧化应激相关的肌肉疾病的基础机制。