Age-dependent decrease in renal glucocorticoid receptor function is reversed by dietary restriction in mice.

Abstract

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.