Defining molecular alterations in apoptotic cell clearance signaling in the aging immune system

2011 new Scholar Award in aging

Apoptosis is a form of programmed cell death necessary for the deletion of damaged, defective or expired cells. Cells undergoing apoptosis must be removed swiftly in order to prevent leakage of potentially toxic and inflammatory contents from the expired cells into the surrounding tissue. A primary means for this removal is phagocytosis- a complex and highly efficient process whereby healthy cells (phagocytes) first “find” then “eat” the dying cells. In addition to the physical removal of cell debris, this process also actively shapes the immune response and local tissue environment by suppressing inflammation and promoting immune tolerance and tissue homeostasis.

An array of degenerative diseases, including atherosclerosis, age-associated inflammation and autoimmunity and Alzheimer’s disease are associated with excess numbers of uncleared apoptotic cells in affected tissues. However, very little is known about how the clearance process changes with age or how this process impacts the initiation and progression of degenerative diseases. Recent advances in our understanding of the molecular and cellular events that control apoptotic cell clearance have made it possible to study the relationship between aging and cell clearance, thus opening up a fascinating and under-explored area of aging research. The goal of this project is to define age-associated changes in key signaling events that regulate the “find,” “eat” and immune resolution phases of the apoptotic cell clearance process. We will study changes in clearance signaling pathways in specific immune phagocyte populations- macrophages and dendritic cells- in aging animals. We anticipate that this work will aid in the development of novel approaches to control age-related disease initiation and activity through the targeted modulation of the pathways that control the clearance of apoptotic cells.

Michael Elliott Ph.D.
University of Rochester