Caloric restriction increases the expression of heat shock protein in the gut

Objective: The authors determined whether caloric restriction (CR), either acutely or chronically, alters heat shock protein 70 (hsp70) gene expression in the gut. Summary Background Data: Caloric restriction prolongs the life span and delays age related disease (e.g., cancer) in mammals; the mechanisms responsible for these effects are not known. Heat shock proteins are a group of stress responsive genes of which the most prominent member is hsp70. Methods: In the first experiment, adult (4-month old) rats (n = 3/group) were killed after a 48-hour fast or 6 and 24 hours after refeeding. In addition, three rats (controls) were killed without fasting or refeeding. The stomach was removed and RNA was extracted for hsp70 gene expression in the second experiment, aged (22 to 26-month-old) rats were fed ad libitum (AL) or a CR diet (60% calorie intake of AL diet). Rats were killed, the stomach and duodenum were removed, and RNA was extracted for determination of hsp70 gene expression. Results: In the first experiment, hsp70 mRNA levels were increased approximately threefold in the stomach of rats fasted for 48 hours; levels decreased to control values by 6 and 24 hours after refeeding. In the second experiment, hsp70 mRNA levels were increased significantly in both the stomach and duodenum of aged CR rats compared with AL controls. Conclusions: The authors have demonstrated that hsp70 mRNA levels are increased in the proximal gut of young and old rats, either acutely (with fasting) or with CR. Increased expression of the cytoprotective hsp70 gene in the gut may provide a possible cellular mechanism for the beneficial effects noted with CR.