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.

Interdependence of the peripheral metabolism of glucocorticoids and thyroid hormones under calorie deficit in rats at different ages

“…On the other hand, a lower renal GR concentration was found in 20-month-old fed mice as compared with 5-month-old mice. Interestingly, dietary restriction (feeding the animals on alternate days for three months) upregulated liver GRs in older mice (Sharma and Dutta, 2006). Lower GR concentrations were also observed in the livers of old 120-week-old mice, as compared with young 4-week-old ones (Ranhotra and Sharma, 2001).…”

“…Various laboratories have shown that calorie restriction (CR) significantly extends the life span in different groups of animals. Some of the effects of dietary restriction, such as protection against insulin-dependent diabetes in rodents, anti-inflammatory and antineoplastic effects, neurological impairments, and reproductive senescence, are parallel to the consequences of elevated levels of GCs (Sharma and Dutta, 2006). During calorie restriction, a decrease in thyroid activity, coupled with a decrease in liver 5'deiodination and an increase in 5 deiodination, among others, has been observed.…”

Late onset of dietary restriction reverses age-related decline of malate–aspartate shuttle enzymes in the liver and kidney of mice

“…In an earlier report from this laboratory, it has been shown that an age-dependent decrease in renal glucocorticoid receptor function is reversed by DR in mice. Glucocorticoids are gluconeogenic hormones and their increased function during late onset DR in older animals may provide better adaptability of kidney in such responses (Sharma and Dutta 2006).…”