Investigating senescent cell fragmentation as a new contributor to aging and disease – SenFrag

Cellular senescence is a complex cellular program best known for its role in promoting tissue aging, damage and disease. Critically, the manipulation or elimination of senescent cells is emerging as having significant clinical potential in treating aging and age-associated diseases. However, there are still major gaps in our understanding of how the program of senescence is controlled at the cellular and molecular level, how senescence contributes to disease, and how senescent cells can be identified. Here, we propose a novel and timely project to investigate new cellular features and models of senescence, identified by both partner labs. We will combine the unique expertise of two groups researching senescence, aging and disease models (Cerebral Cavernous Malformation), with the underexplored link with cell adhesion, mechanotransduction and inflammation. This will involve cell and animal models of disease and aging, high-throughput proteomic and genomic profiling, in vivo and live cell imaging, and intricate functional manipulation of senescent cells. This project has the significant potential to uncover new core regulators of the senescence program, and identify how senescence can contribute to aging and disease.