Project 454381

Diabetes and osteoarthritis (OA) are two of the most common diseases affecting approximately 11 million and 4 million Canadians, respectively. Diabetes is associated with several serious complications, including eye disease, nerve damage, foot ulcers, kidney disease, heart attack, and stroke. OA can cause chronic pain, making it challenging for individuals to exercise, walk, and carry out daily activities such as getting dressed or bathing. Furthermore, both diabetes and OA are associated with depression and can significantly impact a person's quality of life. Despite how common and debilitating these conditions are, there is no cure for either. Therefore, we need to understand their underlying causes better to identify more effective treatment targets and earlier detection. Diabetes (specifically type 2 diabetes (T2D)) and OA often occur together, and both are associated with a condition called sarcopenia. Sarcopenia refers to the loss of muscle mass and strength that occurs with aging. We, therefore, thought that sarcopenia and changes within the muscle might provide a common link between T2D and OA. Autophagy is a process that basically "cleans out" damaged components of cells. When autophagy is reduced or not working properly in muscle, damaged cell components accumulate, and this contributes to sarcopenia. This team project aims to determine how problems with muscle autophagy contribute to T2D and OA. To do this, we will study mouse models in which genes regulating autophagy have been altered in muscle. We will also test if we can treat or reverse T2D and OA using gene therapy to correct the defect in autophagy in muscle. Finally, we will take samples of muscle and blood from individuals suffering from these conditions and analyze them to identify common genetic links between T2D and OA to identify new drug targets.