The hallmark of cancer cells are their capacity for unlimited growth and their potential to invade other tissues. In contrast, normal cells display a limited capacity for growth and then undergo a process called cellular senescence or aging. Immortal cells, those with an unlimited lifespan, have escaped from normal aging controls. Such an escape mechanism may also be one of the major changes leading normal cells to become malignant tumors. Consequently, an understanding of the genes and mechanisms involved in aging and immortality would provide information about important steps in the development of cancer. Recent experimental evidence shows that several genes originally discovered as tumor suppressors, p53 and an RB-like protein, are involved in regulating cellular senescence. The long term objective is to define the molecular basis of cellular senescence in human fibroblasts and epithelial cells, with the long term goal of applying this knowledge to the biology of cancer. By identifying the protein(s) involved in cellular senescence, the proposed research should result in a better understanding if the molecular biology of human aging and cancer.