Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic"-National Institute of Republic of Serbia, University of Belgrade, Bul. despota Stefana 142, 11060 Belgrade, Serbia.
Department of Neurophysiology, Institute for Biological Research "Sinisa Stankovic"-National Institute of Republic of Serbia, University of Belgrade, Bul. despota Stefana 142, 11060 Belgrade, Serbia.
Nutrients. 2021 Dec 17;13(12):4526. doi: 10.3390/nu13124526.
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 Ser 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, , and , confirming its anti-inflammatory and anti-apoptotic effects. Along with an increase in the levels of , our study provides additional evidences that food restriction affects cortical responsiveness to glucocorticoids during aging.
限制食物摄入对衰老和与衰老相关的病理有许多有益的影响，这一点已得到充分证实。此外，短期和长期的食物限制方案都会导致循环中糖皮质激素水平升高，糖皮质激素是肾上腺产生的应激激素，也会对大脑造成有害影响。在本研究中，我们研究了长期食物限制对 18 个月和 24 个月大的大鼠大脑皮层中糖皮质激素激素/糖皮质激素受体 (GR) 系统在衰老过程中的影响。自由进食的老年大鼠皮质酮水平升高。食物限制进一步增加了其水平，同时 11β-羟甾体脱氢酶 1 水平也增加。然而，在限制食物的动物中，GR 的丝氨酸磷酸化水平没有改变，与 CDK5 水平不变、Hsp90 减少以及 GR 功能的负调节因子 FKBP51 增加一致。此外，我们的数据表明，减少食物摄入可以防止与年龄相关的 NFκB、 和 的水平增加，证实了其抗炎和抗凋亡作用。随着水平的增加，我们的研究提供了更多的证据，表明食物限制会影响大脑对衰老过程中糖皮质激素的反应。
