Błaszczyk Janusz Wiesław
Department of Human Motor Behavior, Jerzy Kukuczka Academy of Physical Education, 40-065 Katowice, Poland.
Metabolites. 2020 Nov 7;10(11):450. doi: 10.3390/metabo10110450.
There is a growing body of evidencethat indicates that the aging of the brain results from the decline of energy metabolism. In particular, the neuronal metabolism of glucose declines steadily, resulting in a growing deficit of adenosine triphosphate (ATP) production-which, in turn, limits glucose access. This vicious circle of energy metabolism at the cellular level is evoked by a rising deficiency of nicotinamide adenine dinucleotide (NAD) in the mitochondrial salvage pathway and subsequent impairment of the Krebs cycle. A decreasing NAD level also impoverishes the activity of NAD-dependent enzymes that augments genetic errors and initiate processes of neuronal degeneration and death.This sequence of events is characteristic of several brain structures in which neurons have the highest energy metabolism. Neurons of the cerebral cortex and basal ganglia with long unmyelinated axons and these with numerous synaptic junctions are particularly prone to senescence and neurodegeneration. Unfortunately, functional deficits of neurodegeneration are initially well-compensated, therefore, clinical symptoms are recognized too late when the damages to the brain structures are already irreversible. Therefore, future treatment strategies in neurodegenerative disorders should focus on energy metabolism and compensation age-related NAD deficit in neurons. This review summarizes the complex interrelationships between metabolic processes on the systemic and cellular levels and provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.
越来越多的证据表明，大脑衰老源于能量代谢的下降。特别是，神经元对葡萄糖的代谢稳步下降，导致三磷酸腺苷（ATP）生成日益不足，这反过来又限制了葡萄糖的摄取。线粒体补救途径中烟酰胺腺嘌呤二核苷酸（NAD）缺乏加剧，随后三羧酸循环受损，引发了细胞水平上这种能量代谢的恶性循环。NAD水平降低还会削弱NAD依赖酶的活性，增加基因错误，并引发神经元变性和死亡过程。这一系列事件是几个神经元能量代谢最高的脑结构的特征。具有长无髓轴突的大脑皮层和基底神经节神经元以及具有众多突触连接的神经元尤其容易衰老和发生神经变性。不幸的是，神经变性的功能缺陷最初得到了很好的代偿，因此，当脑结构损伤已经不可逆转时，临床症状才被发现，为时已晚。因此，神经退行性疾病未来的治疗策略应侧重于能量代谢和弥补神经元中与年龄相关的NAD缺乏。本综述总结了全身和细胞水平代谢过程之间的复杂相互关系，并就如何降低神经变性风险和保护老年人免受神经退行性疾病侵害提供了指导。
