BACKGROUND Prostate cancer is the most frequently diagnosed neoplasm and the second leading cause of cancer-related mortality in men. Although the incidence of prostate cancer increases with age, the link between aging and prostate cancer is poorly understood. METHODS Affymetrix oligonucleotide microarrays were used to analyze the mRNA expression levels in the dorsolateral prostates from 6- and 18-month-old ACI rats. Real-time RT-PCR and immunohistochemistry was performed to validate microarray data in a select set of genes. RESULTS Microarray analysis revealed changes in gene expression associated with inflammation, oxidative stress, tissue remodeling, and energy metabolism. Most of these changes have been related to increased proliferative status of the prostate, anti-apoptosis, activated stroma, and alteration of the energy metabolism. CONCLUSIONS Age-associated alterations in the gene expression profile may put the aging prostate in risk for the initiation, promotion, and progression of neoplastic transformation in both our animal model and humans. © 2004 Wiley-Liss, Inc.