Human aging is correlated with reduced proliferation of various cell types, a phenomenon that can be reproduced in in vitro models of replicative senescence. We study senescence of several human primary cell types by analysis of age-related changes in gene expression and gene function. In a second approach, my group uses immortalizing oncogenes derived from DNA tumor viruses as genetic tools to study genetic and biochemical mechanisms underlying the progression of cells into senescence. Specifically, our work is guided by the hypothesis that cellular proteins binding to the E7 gene product of human papillomavirus are good candidates for senescence-inducing cellular factors. For several of these cellular factors, e.g. the inhibitor of cyclin-dependent kinases p21(WAF-1), a functional role in senescence has already been demonstrated.