Abstract
Numerous beneficial effects of food restriction on aging and age-related pathologies are well documented. It is also well-established that both short- and long-term food restriction regimens induce elevated circulating levels of glucocorticoids, stress-induced hormones produced by adrenal glands that can also exert deleterious effects on the brain. In the present study, we examined the effect of long-term food restriction on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the cortex during aging, in 18- and 24-month-old rats. Corticosterone level was increased in the cortex of aged ad libitum-fed rats. Food restriction induced its further increase, accompanied with an increase in the level of 11β-hydroxysteroid dehydrogenase type 1. However, alterations in the level of GR phosphorylated at Ser232 were not detected in animals on food restriction, in line with unaltered CDK5 level, the decrease of Hsp90, and an increase in a negative regulator of GR function, FKBP51. Moreover, our data revealed that reduced food intake prevented age-related increase in the levels of NFκB, gfap, and bax, confirming its anti-inflammatory and anti-apoptotic effects. Along with an increase in the levels of c-fos, our study provides additional evidences that food restriction affects cortical responsiveness to glucocorticoids during aging.
Highlights
Moderate reduction in food intake [food restriction (FR)] is widely accepted as one of the few effective approaches to extend lifespan, slow-down physiological aging, and to delay the onset or reduce the severity of age-associated diseases [1,2]
This is in line with well-established detrimental effects of chronic exposure to excess glucocorticoids on the brain, which were further associated with learning and memory impairments, and various pathologies including age-related neurodegenerative diseases, dementia, and psychosis [18,19,20,21]
The aim of the present study was to provide a broad analysis of the effects of food restriction on cortical responsiveness to glucocorticoids, relevant changes in glucocorticoid hormone/glucocorticoid receptor (GR) system, and to reveal the pattern of these changes during aging in order to identify their involvement in age-related cognitive decline and numerous well-known neuroprotective effects of FR
Summary
Moderate reduction in food intake [food restriction (FR)] is widely accepted as one of the few effective approaches to extend lifespan, slow-down physiological aging, and to delay the onset or reduce the severity of age-associated diseases [1,2]. Among specific cellular and molecular mechanisms that may account for beneficial anti-aging and neuroprotective effects of FR, the most extensively reported are the decrease in metabolic rate, increase in insulin sensitivity, and those resulting in promoting anti-oxidative and anti-inflammatory capacity [1] Both acute and long-term FR regimens are known to induce moderate elevation of glucocorticoids in the blood [13,14,15]. The majority of age-related studies were, focused on the role of dysregulated GR signaling in impaired spatial memory and structural changes in the hippocampus [31,32,37,38], with just a few studies addressing relevant alterations in the cortex, brain region highly vulnerable to the effects of stress and aging and involved in cognition and regulation of the HPA axis [27,28,29,33]. The aim of the present study was to provide a broad analysis of the effects of food restriction on cortical responsiveness to glucocorticoids, relevant changes in glucocorticoid hormone/glucocorticoid receptor (GR) system, and to reveal the pattern of these changes during aging in order to identify their involvement in age-related cognitive decline and numerous well-known neuroprotective effects of FR
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
