Shankar S K
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore - 560 029, Karnataka, India.
Indian J Pathol Microbiol. 2010 Oct-Dec;53(4):595-604. doi: 10.4103/0377-4929.71995.
Normal aging of the nervous system is associated with some degree of decline in a number of cognitive functions. With the present day attempts to increase the life span, understanding the metabolic interactions and various mechanisms involved in normal neuronal aging continues to be a challenge. Loss of neurons is now recognized to be more modest than the initial estimates suggested and the loss only affected some of the specific neuroanatomical areas like hippocampus and prefrontal cortex. Individual neurons in addition show reduced size of dendritic and axonal arborization. Neurons have significant homeostatic control of the essential physiological functions like synaptic excitability, gene expression and metabolic regulation. Deviation in these normal events can have severe consequences as observed in aging and neurodegeneration. Based on experimental evidence, the evolution of aging is probably the result of altered metabolic triad: the mitochondria, reactive oxygen species and intracellular calcium homeostasis. Perturbations in the metabolic and functional state of this triad lead to a state of decreased homeostatic reserve, where the aged neurons still could maintain adequate function during normal activity. However, these neurons become vulnerable to the stress of excessive metabolic loads associated with spells of ischemia, trauma progressing to neuronal degeneration. Age-related neuronal dysfunction probably involves a host of subtle changes involving the synapses, receptors, neurotransmitters, cytological alterations, electrical transmission, leading to cognitive dysfunction. An exaggeration of it could be the clinical manifestation of dementia, with intraneuronal accumulation of protein aggregates deranging the metabolic state. This review deals with some of the structural, functional and metabolic features of aging nervous system and discusses briefly the functional consequences.
神经系统的正常衰老与多种认知功能在一定程度上的衰退有关。随着当今延长寿命的尝试，了解正常神经元衰老过程中涉及的代谢相互作用和各种机制仍然是一项挑战。现在人们认识到神经元的丧失比最初估计的要轻微，而且这种丧失只影响了一些特定的神经解剖区域，如海马体和前额叶皮层。此外，单个神经元的树突和轴突分支大小也会减小。神经元对突触兴奋性、基因表达和代谢调节等基本生理功能具有重要的稳态控制。正如在衰老和神经退行性变中所观察到的，这些正常事件的偏差可能会产生严重后果。基于实验证据，衰老的演变可能是代谢三联体改变的结果：线粒体、活性氧和细胞内钙稳态。这个三联体的代谢和功能状态的扰动会导致稳态储备减少的状态，在这种状态下，衰老的神经元在正常活动期间仍能维持适当的功能。然而，这些神经元容易受到与缺血发作、创伤相关的过度代谢负荷的压力，进而发展为神经元变性。与年龄相关的神经元功能障碍可能涉及一系列细微的变化，包括突触、受体、神经递质、细胞学改变、电传递，从而导致认知功能障碍。其过度表现可能是痴呆的临床表现，神经元内蛋白质聚集体的积累会扰乱代谢状态。这篇综述探讨了衰老神经系统的一些结构、功能和代谢特征，并简要讨论了其功能后果。
