Moderate Caloric Restriction Alters the Subcellular Distribution of Somatostatin mRNA and Increases Growth Hormone Pulse Amplitude in Aged Animals

Abstract

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.

Leptin alters the response of the growth hormone releasing factor- growth hormone--insulin-like growth factor-I axis to fasting

“…IGF-I is also depressed (Underwood et al 1986, Vance et al 1992, Ohashi et al 1995 during fasting. It has been recently reported that impaired somatostatin distribution and release may also contribute to changes seen in the GH axis in nutritionally deprived animals (Aguila & McCann 1987, Sonntag et al 1995.…”

Insights into a role of GH secretagogues in reversing the age-related decline in the GH/IGF-I axis

“…One problem common to many studies on aging is that different animal strains are used and submitted to different nutritional conditions. It has been reported that moderate caloric restriction altered the subcellular distribution of SS mRNA and increased GH pulse amplitude in aged animals (53).…”

Dietary restriction maintains the basal rate of somatotrope renewal in later life in male rats

“…The synthesis and secretion of GHRH in the hypothalamus is thought to be reduced in aged rats fed ad libitum (23,24). There is no direct evidence that GHRH is secreted in aged DR animals in a fashion similar to that observed in young counterparts fed ad libitum However, a recent study reported that pulsatile secretion of GH similar to that in young AL rats is present in aged DR rats, but not in aged AL rats (25), suggesting that GHRH is secreted efficiently in DR rats in later life. Thus, preservation of the hypothalamic function may be attributed to maintaining the basal rate of somatotrope renewal in aging DR rats, leading to the protection of impaired pituitary response to GHRH during aging.…”