Grant: Operating Grant

The proposed study seeks to understand the role of reactive oxygen species (ROS) in the aging process. ROS are also often called 'free radicals' and are important regulators of the function of cells, but they are also potentially toxic. In the past, people have believed that it is the toxicity of ROS that is most important in the aging process. However, we have recently shown that it is the action of ROS as regulators that might be the most important. If fact we have shown that ROS can have a beneficial effect and act to increase lifespan. Furthermore, we have shown that, in this role, ROS act through a mechanism that is normally used by our bodies to get rid of damaged cells. Cells die when the mechanism is turned on and are later replaced by new cells. But, when the action of ROS modulates the activation of this mechanism in response to damage, the result is an increase in stress resistance and repair, which helps the cell to overcome the damage. Such an alternative use of the mechanism might be important for cells that cannot be replaced, which is true for example for many brain and spinal cord cells. When such cells are lost in disease situations this results in permanent cognitive or movement deficits because they cannot be replaced. In the proposed study we will try to understand in detail how and when ROS act on the mechanism, and how this can sometimes result in cell death and sometimes in increased cell survival. Understanding this will open the door to learn how to modulate the action of the mechanism in a way that is favorable for cell survival, for example in brain diseases.