The long term goal of this work is to define a molecular basis for the process of cellular aging by identifying and characterizing age specific changes in cell surface components. In particular we will use monoclonal antibodies, directed against human fibroblast cell surface antigens, to identify antigens that are expressed as a function of cellular age. Once identified, by gel electrophoresis and immunofluorescence, we will determine the role of extracellular growth factors and matrix components on antigen expression. Further, we will use the antibodies to select homogeneously aged cell populations. In addition to the work with human fibroblasts we will examine parameters of in vitro age in cultured vascular smooth muscle cells. A correspondence between smooth muscle cell activation and cardiovascular disease has been implied from earlier work. We find that, in culture, one step of that activation stage is absent in aged cells. We propose to examine the mechanism of regulation of that step by identifying antigenic and biochemical markers for its initiation. Further, we propose to determine the role of the extracellular matrix in smooth muscle cell differentiation and aging.
