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

Although growth hormone secretion decreases with age in both animals a nd man, its potential role in the regulation of biological aging is un known. In a series of experiments, age-related changes in growth hormo ne secretory dynamics were compared in ad libitum fed and moderately c alorically restricted male Brown-Norway rats. These animals exhibit an increase in both mean and maximal lifespan in response to caloric res triction. In addition, the subcellular distribution of somatostatin mR NA was compared since previous data indicated that somatostatin secret ion increases with age and has an important role in the age-related de cline in growth hormone pulse amplitude. In ad libitum fed animals, gr owth hormone secretory dynamics decreased with age and were associated with a decline in total somatostatin mRNA levels. However, analysis o f somatostatin mRNA precipitating with polyribosomes revealed a signif icant increase with age (p < 0.05). When data were expressed as polyso mal/total mRNA, levels in 25-month-old animals increased 94 and 104% c ompared 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 pul se amplitude increased and was indistinguishable from young ad libitum fed animals. In addition, the moderate caloric-restricted animals fai led 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 reg ulation of somatostatin mRNA at the translational level may be a contr ibuting factor in the decrease in growth hormone secretion observed in aging animals. In addition, we conclude that part of the actions of m oderate caloric restriction in delaying physiological changes associat ed with age are related to increased growth hormone secretion.