Cellular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Antioxid Redox Signal. 2013 Sep 10;19(8):813-22. doi: 10.1089/ars.2012.4996. Epub 2013 Feb 5.
A decline in both cognitive and motor functions is one of the characteristics of aging. This results in changes in learning and memory, as well as deficits in balance and coordination that significantly impact the quality of life. Importantly, age is the greatest risk factor for a number of neurodegenerative diseases. Alterations in redox homeostasis, protein modification and processing, mitochondrial function, and the immune response have all been implicated in the decline of the aging brain.
Brain glutathione (GSH) decreases with age in humans, and a loss of GSH can impact cognitive function. Decreases in GSH are also associated with microglial activation and endothelial dysfunction, both of which can contribute to impairments in brain function. Changes in redox homeostasis can also potentiate the accumulation of advanced glycation endproducts, resulting in defects in protein processing and function as well as a further increase in inflammation.
We argue here that many of the changes in brain function associated with age are linked through GSH metabolism.
Further research focused on better understanding how age affects GSH homeostasis with a particular emphasis on the key transcription factors involved in GSH metabolism is needed.
认知和运动功能的下降是衰老的特征之一。这导致学习和记忆的变化，以及平衡和协调的缺陷，极大地影响生活质量。重要的是，年龄是许多神经退行性疾病的最大风险因素。氧化还原平衡、蛋白质修饰和加工、线粒体功能和免疫反应的改变都与衰老大脑的衰退有关。
人类大脑中的谷胱甘肽 (GSH) 随年龄的增长而减少，GSH 的损失会影响认知功能。GSH 的减少也与小胶质细胞激活和血管内皮功能障碍有关，这两者都可能导致大脑功能障碍。氧化还原平衡的改变也会增强晚期糖基化终产物的积累，导致蛋白质加工和功能的缺陷以及炎症的进一步增加。
我们在这里认为，与年龄相关的许多大脑功能变化都与 GSH 代谢有关。
需要进一步研究，以更好地了解年龄如何影响 GSH 动态平衡，特别是要特别强调参与 GSH 代谢的关键转录因子。
