Age-associated reduction of stimulatory effect of ghrelin on food intake in mice

Abstract Aging is associated with a progressive decrease in appetite and food intake. We focused on the age-associated changes of the stimulatory effect of the appetite-regulating peptide, ghrelin. Food intake and the concentrations of acyl ghrelin and desacyl ghrelin in the plasma and in the stomach were measured with and without overnight fasting in young and old mice. Moreover, the food intake in response to the intraperitoneal administration of graded doses of acyl ghrelin was compared between young and old mice. Fasting drives food intake in young mice, but not in old mice. The concentrations of acyl ghrelin and desacyl ghrelin in the plasma and in the stomach were higher in the old mice than in the young mice. Food intake did not increase in old mice when stimulated by the administration of 1–3 nmol of acyl ghrelin, which could produce a significant increase in food intake in young mice. In conclusion, food intake did not increase in old mice after either overnight fasting or the administration of acyl ghrelin. The release and synthesis of ghrelin seem to be rather higher in old mice compared to young mice. These increases might be the results of compensation for the decline of receptor (and/or post-receptor) functions.