EXPRESSION OF HEAT-SHOCK GENES IN HEPATOCYTES IS AFFECTED BY AGE AND FOOD RESTRICTION IN RATS

The objective of this study was to determine how food restriction alte red the age-related changes in the basal and heat-induced expression o f heat shock genes (hsc70, grp78, and ubiquitin) by hepatocytes isolat ed from young (4 to 6 mo old) and old (26 to 28 mo old) male Fischer 3 44 rats. The basal levels of the mRNA transcripts for hsc70 and ubiqui tin were similar for hepatocytes isolated from young and old rats fed with free access to the diet (control) or from rats fed a restricted d iet (40% restriction of food intake). However, the induction of the mR NA transcripts for hsc70 and ubiquitin by a heat shock (42.5 degrees C for 30 min) was significantly higher for hepatocytes isolated from ol d rats fed the restricted diet compared with old rats fed with free ac cess to the diet. The changes in hsc70 mRNA levels were paralleled by similar changes in hsc70 transcription by isolated nuclei; therefore, the greater induction of hsc70 expression by food restriction results from changes in the transcription of hsc70 gene. In contrast with hsc7 0 and ubiquitin, the basal levels of grp78 were reduced with age and b y food restriction. Therefore, the effect of aging and food restrictio n on the basal and heat-induced expression of heat shock genes varies considerably from gene to gene.