Cellular and molecular correlates of the decline in responsiveness of cartilage and thymus to growth hormone in aged animals

Abstract

The responses in vitro of cartilage to somatomedin and of thymocytes to growth hormone have been studied in tissues derived from rats of various ages. The basal and somatomedin stimulated incorporation of radioactive proline into proteins and of sulphate into mucopolysaccharides diminishes markedly with age. Chondrocytes per unit area in cartilage of old rats are about 4- to 5-fold reduced in number as compared to those in cartilage from 1-day old rats. The organ size and yield of thymocytes are reduced in aged rats. Besides the fall in number of cells, the average metabolic activity of cells as measured by uridine incorporation into RNA in vitro is also diminished. There is a progressive decline in stimulation by growth hormone of uridine incorporation in isolated thymocytes with age. Immunocytochemical studies reveal the location of the hormone along the membrane. The amount of the hormone bound by thymocytes, estimated by immunoenzymatic methods is 3- to 9-fold lower in thymocytes from 14-months old rats as compared to similar preparations from 4-week old rats. Thymocytes from both young and old rats are composed of subpopulations, one of which binds growth hormone. The proportion of the hormone binding cells is higher in thymocytes from young rats as compared to those from aged animals.