The objectives of this project are to investigate the mechanisms of aging at the cellular level in a differentiated endocrine cell type, the adrenocortical cell. Our aim is to develop a culture system that will allow this endocrine cell to complete its culture life span with preservation of all normal differentiated features. This will allow us to define the factors that are responsible for the observed age-related changes in cell surface receptors and in the enzymes responsible for steroid synthesis. To date, bovine cells have been used in these studies. During the coming year, we will attempt to establish a fetal human adrenal culture system to extend these studies from cattle to man. Our work during the past year has demonstrated that changes in differentiated functions which occur during cell culture aging of bovine adrenocortical cells, even though such changes may be irreversible, may be the result of the environment to which the cells are subjected. "Environment" here includes such features as cell density as well as changes in the microenvironment caused by the cells themselves, such as the secretion of steroids. These studies contribute to an understanding of the nature of cell culture aging and its relevance to in vivo aging.