Acute exercise signaling in old and young muscle

Exercise is the most effective treatment for sarcopenia, the age-related loss of muscle mass and function. Despite its positive effects, many studies indicate that adaptive signaling with exercise is altered or attenuated with age. We and others have found that aging muscle presents with increased mitochondrial reactive oxygen species (ROS) generation, decreased mitochondrial function, and an oxidized redox status, and tends to be more susceptible to exercise related injury and inflammation. Evidence suggests that exercise results in increased oxidative modifications to protein thiols, which may alter the activity of transcription factors, kinases, and the function of contractile proteins. In this study, we are investigating the types of post-translational modifications that occur in muscle after a single bout of intense muscle stimulation, and how these modifications differ with age. We will use targeted molecules to interrogate the role of mitochondrial ROS and NADPH oxidase-derived ROS on exercise signaling. Combined with sophisticated proteomics techniques, and high resolution respirometry and magnetic imaging, this study will help elucidate the mechanisms associated with the altered exercise responsiveness with age and provide us with therapeutic targets for the treatment and prevention of sarcopenia.

This study is being performed in collaboration with Ravneet Vohra and Donghoon Lee (Radiology, UW), Miguel Martin Perez and Judit Villen (Genome Sciences, UW), and Jicheng Duan and Weijun Qian (Pacific Northwest National Labs, Richland, WA).

Mitochondrial redox in skeletal muscle aging

Redox homeostatis and signaling with age

Chronic domoic acid exposure

Modeling human domoic acid consumption levels