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.

The effects of age and dietary restriction (alternate days of feeding for 3 months) on the concentration, activation, and DNase I digestion of nuclear-bound glucocorticoid receptors (GRs) in the kidney of male mice at two different ages (5 months as adult and 20 months as old) were investigated. A significant decrease (30%) in the concentration of renal GRs was observed in older ad libitum (AL)-fed mice as compared to the adult mice. Dietary restriction (DR) of older mice significantly increased (28%) the level of GRs as compared to the AL-fed control animals. The affinity of the receptor for the hormone remained the same for both AL- and DR-fed animals at both ages. Scatchard and slot blot analyses of the data confirmed the decreased level of renal GRs in older mice compared to the adult mice as well as an increased level of receptor in older DR mice. Activation studies of GRs by both salt and heat indicated a decreased (15-20%) activation of renal GRs in older animals compared to the adult mice in the AL-fed group. It was further observed that DR significantly enhanced (30%) the degree of both salt- and heat-dependent activation of GRs in older animals compared to the AL-fed animals of the age-matched group. DNase I digestion and extraction of nuclear-bound GR complexes showed a lower degree (26%) of extraction in older AL-fed animals compared to the adult animals. However, DR did not alter the pattern of digestibility of bound GR complexes. These above findings indicate that DR could reverse the decrease of GR function in older animals and may provide better adaptability of kidney in water and electrolyte balance.

The specific binding of [3H] dexamethasone to its receptor, activation of the hormone-receptor complexes and DNase I digestion of nuclear bound hormone-receptor complexes were studied in the liver of mice during dietary restriction (alternate days of feeding for 3 months) compared to animals fed ad libitum. Results indicate an increase of receptor level (fmol/mg protein) in the diet-restricted (DR) animals as compared to those fed ad libitum (AL). Scatchard analyses confirm the increase in the level of receptors in DR animals, while the affinity (Kd) remained same in both groups of mice. Protein slot-blot analysis also depicts the increase of the receptor level in DR fed compared to the AL fed animals. The extent of temperature- and salt-dependent activation of receptors showed no marked difference in AL- and DR-fed mice. DNase I extraction of bound hormone-receptor complexes from nuclei revealed similar pattern of digestion in both groups of animals.