Identifying the Changes in Gene Profiles Regulating the Amelioration of Age-Related Oxidative Damages in Kidney Tissue of Rats by the Intervention of Adult-Onset Calorie Restriction

Abstract

This study was initiated to investigate gene expression profiles that are involved in the molecular mechanisms regulating the amelioration of age-related oxidative damages in male Fischer-344 rats (12 months) through adult-onset calorie restriction (CR) intervention for 6 months. The adult-onset CR was initiated with 10 and 25% restriction for the first and second weeks, respectively, and then maintained at 40% throughout the experiment. The adult-onset CR significantly (p < 0.05) decreased urinary 8-isoprostane and protein carbonyl in kidney for the markers of lipid peroxidation and protein oxidation, respectively, in rats from the CR group when compared with control group. Based on Yu's and Melk's methods, the age-related renal pathological changes in the kidney of rats from CR group were retarded by adult-onset CR. Such changes could result from the decrease of plasminogen activation inhibition-1 and clusterin and the increase of kallikrein mRNA expressions significantly (p < 0.05) in the kidneys of rats from the CR group. They were further confirmed by quantitative RT-PCR. Moreover, inflammatory response pathway was down-regulated significantly (p < 0.05) in rats from the CR group, while fatty acid synthesis, mitochondrial fatty acid betaoxidation, glycolysis, and gluconeogenesis were considerably up-regulated in kidney tissue of rats. In conclusion, the adult-onset CR could retard the age-related oxidative damages and renal pathological changes due to variations in gene expressions and biological pathways.