Thesis: The Effects of Reactive Oxygen Species (ROS) on Insulin-like Growth Factor 1 (IGF-1) Signaling: Implication in Age Related Skeletal Muscle Wasting
Oxidative stress, caused by the activities of a group of reactive compounds known as ROS, has been proposed as a key intermediary in age-related skeletal muscle wasting (sarcopenia). ROS can impact on signal transduction networks as many signalling proteins can be reversibly modified by ROS. We propose that ROS can interact with signalling pathways to depress protein synthesis and enhance protein catabolism. In the IGF-1 signalling pathway that regulates protein synthesis and muscle growth, AKT and phosphatases can be reversibly oxidized by ROS, leading to activation or inhibition of the pathway. We hypothesize that ROS contribute to sarcopenia via interference with IGF-1 signalling.
The aim of this study is to investigate the effects of ROS on IGF-1 signalling in skeletal muscle using both tissue culture (C2C12 myotubes) and in vivo (transgenic mice with ubiquitous overexpression of mitochondrial catalase) studies.
Why my research is important
This research will extend our knowledge on the role of reactive oxygen species (ROS) in age-related skeletal muscle wasting by studying their interaction with the Insulin-like Growth Factor 1 (IGF-1) signaling pathway. It has become evident in the past decade that ROS are not simply by-products of metabolism, but also play critical role in signal transduction networks. Clarification of the interactions between ROS and the IGF-1 signaling pathway in skeletal muscle (research still in infancy) will provide new insights into the molecular mechanisms involved in the control of oxidative stress in muscle wasting and identify new targets for the development of novel antioxidant therapies. This research will also ultimately allow us to test in vivo if decreased oxidative stress attenuates age-related skeletal muscle wasting.