Genetic dissection of the insulin/IGF1-mTOR pathway in mammalian aging
Over the last two decades, manipulation of the Insulin and the mechanistic target of rapamycin complex 1 (mTORC1) pathways has emerged as one of the most promising approaches to increase the healthspan and lifespan. Using genetic, pharmaceutical, and dietary approaches, studies have demonstrated that silencing these molecular pathways can protect from age-related metabolic decline, muscle loss and that it can extend lifespan of organisms from worms to mice. However, the molecular mechanisms and whether these two pathways are linked in their influence over mammalian longevity remains largely unknown. In this proposed research, Dr. Cormerais will use a novel genetically engineered mouse model that specifically disconnects these two pathways. This project will seek to determine if reduced insulin signaling in mammals favors increased health-span and longevity due primarily to a reduction in mTORC1 signaling. These studies will provide critical new insight into the consequences of the Insulin-mTORC1 pathway during aging.
