Senescence is one cellular response to stress like wounds at the tissue level or DNA damage to a cell. When we are young, our immune system clears out senescent cells. But as we age, our immune system loses this capacity and senescent cells accumulate. They cause chronic sterile inflammation, fueling most chronic diseases and frailty. We can help the body clear senescent cells, potentially delaying disease and frailty with senolytic drugs. The Niedernhofer lab is testing a large variety of approaches to clear senescent cells, while mapping and characterizing senescent cells in human and mouse tissues to optimize senolytics. For this research, we developed mouse models of diabetes, chronic kidney disease, neurodegenerative diseases, lung fibrosis, liver fibrosis, age-related macular degeneration, and cardiomyopathy.
Another important aspect of our research is studying diseases of accelerated aging caused by genome instability like xeroderma pigmentosum and Cockayne syndrome. Our hope is to deploy therapeutics that target aging biology, like senolytics, to help these patients. Additionally, we develop assays to measure DNA repair to help with diagnosis of these diseases.