BACKGROUND. Aging, a universal phenomenon of all living organisms, is one of the least clearly understood biological processes. Changes in expression (either increase or decrease) have been noted in various genes with aging. The expression of antioxidant enzymes and their ability to limit oxygen-derived free radical damage with aging has been the focus of much investigation; however, a systematic analysis of expression patterns has not been performed. The liver plays a key role in overall homeostasis; therefore, alteration of hepatic gene expression and function with aging may greatly affect outcome from stress (eg, acute injury or surgery). The purpose of our study was to assess changes in gene expression patterns in aged liver of both rat and human using gene array analysis.
METHODS. 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 (human array = 12, 626 genes and rat array = 8, 799 genes).
RESULTS. Three-fold or greater change in gene expression was noted in 582 genes in the aged rat liver (552 genes increased and 30 genes decreased) and 192 genes in the aged human liver (43 genes increased and 149 genes decreased). Comparison of gene expression changes in both the rat and human aged liver demonstrated some similar patterns of gene expression. For example, the antioxidant gene UDP-glucuronosyltransferase was increased 3-fold in the human liver and 29-fold in the rat liver with aging. Glutathione S-transferase, another antioxidant enzyme important for detoxification, was increased 19-fold and 61-fold in the livers of aged human and rat, respectively. In addition, increases were noted in the expression of the cytochrome P450 family of genes in the aged human liver. In the rat liver, increases were noted in Cu/Zn superoxide dismutase (56-fold), NADH-cytochrome b5 reductase (48-fold) and heat shock protein 70 precursor (32-fold).
CONCLUSIONS. Our findings demonstrate, by gene array methods, changes in the expression pattern of genes in the liver with aging. Concomitant increases in the expression of important antioxidant and stress-related genes were noted in the liver of both the rat and the human. This induction pattern suggests a complex link between changing hepatic detoxification/redox capability and senescence.
