Age-dependent dietary regulation of glucocorticoid receptors in the liver of mice.

Dietary restriction (DR) increases the resistance to different stresses, retards various age-related diseases and extends life span in a variety of animals. Here we have investigated the effect of DR (alternate days of feeding for 3 months) on glucocorticoid receptors (GRs) in the liver of adult (5 months) and old (20 months) male mice. A significant decrease was observed in the level of receptors in old mice (25%) as compared to the adult ones. DR subjected mice of both age groups showed a marked increase in the GR concentration (37% in adult and 31% in old mice) as compared to the ad libitum (AL) fed mice, whereas the affinity remained the same in both groups of animals at both ages. Scatchard analyses and the protein slot blot experiment confirmed the increase in the receptor level in AL and DR fed animals for both age groups. The magnitude of heat and salt activation of GR was higher in the adult mice as compared to the old mice who were fed AL. DR, however, significantly increased (40%) the magnitude of activation of GR in the older mice as compared to the AL fed animals, whereas no such change was observed in the adult animals. Further, DNase I digestion and extraction of nuclear bound GR-complexes showed a higher degree of extraction in adult animals (57%-59%) as compared to the old (31%-33%) animals. Mice subjected to DR revealed no significant change at either age. These findings indicate that DR regulates GR in an age-dependent manner and that it may allow animals to better adapt to metabolic regulation in older ages.