Project 436933

Over 1.5 million of Canadians are affected by osteoporosis, a disease that is caused by weak bones and leads to increased risk of fracture. As the Canadian population ages, the burden of osteoporotic fractures is predicted to increase. One of the hallmarks of age-related bone loss is cellular senescence; a process characterized by cells that can no longer divide. In bone, there is normally a balance between building bone (i.e. bone formation) and destroying bone (i.e. bone resorption). When bone cells senesce, the mechanisms that destroy bone overwhelm the mechanisms that build bone and there is a decrease in bone strength. Like age-related bone loss, there is a decrease in bone strength when bones are not being used, this is called disuse-related bone loss. Whenever we walk or stand, our bones experience pressure (a load) and this helps them to stay strong. In patients who are bedridden or have limited mobility, however, these forces are no longer present and bone strength decreases. When the bone is no longer experiencing these forces, it is said to be unloaded. Age-related bone loss and disuse-related bone loss share many similarities, and the combination of the two can lead to even worse outcomes for elderly patients. Hence, finding ways to prevent either or both types of bone loss is imperative. Senolytic drugs, such as dasatinib and quercetin, are compounds that will selectively kill senescent cells. When administered to aged mice, they are found to be protective of bone strength. To date, the role of senescence on the skeletal system in response to unloading has not been examined. Since, age- and disuse-related bone loss share many similarities, it is possible that senolytics may exert a similar protective effect on disuse-induced bone loss in young and aged mice. The relationship between senescence, disuse and age-related bone loss has the potential to elucidate mechanisms of osteoporosis and identify novel therapeutic targets.