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

点击翻译按钮获取中文摘要

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.