MODERATE CALORIC RESTRICTION ALTERS THE SUBCELLULAR-DISTRIBUTION OF SOMATOSTATIN MESSENGER-RNA AND INCREASES GROWTH-HORMONE PULSE AMPLITUDE IN AGED ANIMALS

Although growth hormone secretion decreases with age in both animals and man, its potential role in the regulation of biological aging is unknown. In a series of experiments, age-related changes in growth hormone secretory dynamics were compared in ad libitum fed and moderately calorically restricted male Brown-Norway rats. These animals exhibit an increase in both mean and maximal lifespan in response to caloric restriction. In addition, the subcellular distribution of somatostatin mRNA was compared since previous data indicated that somatostatin secretion increases with age and has an important role in the age-related decline in growth hormone pulse amplitude. In ad libitum fed animals, growth hormone secretory dynamics decreased with age and were associated with a decline in total somatostatin mRNA levels. However, analysis of somatostatin mRNA precipitating with polyribosomes revealed a significant increase with age (p < 0.05). When data were expressed as polysomal/total mRNA, levels in 25-month-old animals increased 94 and 104% compared to 6- or 16-month-old animals, respectively (p < 0.01). Growth hormone secretory dynamics decreased in young animals maintained on a moderate caloric restricted diet, but by 26 months growth hormone pulse amplitude increased and was indistinguishable from young ad libitum fed animals. In addition, the moderate caloric-restricted animals failed to exhibit the decline in total somatostatin mRNA or the increase in polyribosome-associated somatostatin mRNA characteristic of the ad libitum fed 25-month-old animals. Our results suggest that altered regulation of somatostatin mRNA at the translational level may be a contributing factor in the decrease in growth hormone secretion observed in aging animals. In addition, we conclude that part of the actions of moderate caloric restriction in delaying physiological changes associated with age are related to increased growth hormone secretion.