Aging is one of the least clearly understood biological processes. Alteration of oxidation/reduction (redox) enzymes has been demonstrated with aging; however, a systematic analysis of expression patterns has not been performed. The liver plays a key role in homeostasis and detoxification; therefore alteration of hepatic gene expression with aging may affect outcome after surgery. The purpose of our study was to assess changes in gene expression patterns in aged livers from both rats and humans using gene array analysis. Total RNA was extracted from young (2-month-old) and aged (2-year-old) rat livers, as well as young (1-year-old) and aged (78-year-old) human livers. Gene expression patterns were compared using Affymetrix GeneChip arrays. The expression pattern of selected genes was confirmed by reverse transcription-polymerase chain reaction. A threefold or greater change in gene expression was noted in 582 genes in the aged rat livers and 192 genes in the aged human livers. Comparison of the genes that were increased with aging demonstrated some similar patterns of expression in the rat and human livers, particularly in members of the antioxidant family and the cytochrome P-450 genes. Our findings demonstrate changes in the expression pattern of genes in the liver with aging. Concomitant increases in the expression of important antioxidant and detoxifying genes were noted in the livers of both rats and humans. This induction pattern suggests a complex link between changing hepatic detoxification/redox capability and senescence.