Miller D B, O'Callaghan J P
Chronic Stress and Neurotoxicology Laboratories, TMBB-HELD, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health-CDC-NIOSH, Morgantown, WV 26505, USA.
Ageing Res Rev. 2005 May;4(2):123-40. doi: 10.1016/j.arr.2005.03.002.
Functional loss often occurs in many body systems (e.g., endocrine, cognitive, motor) with the passage of years, but there is great individual variation in the degree of compromise shown. The current focus on brain aging will continue because demographic trends indicate that the average lifespan will show a continued increase. There is increasing emphasis on understanding how aging contributes to a decline in brain functions, cognition being a prime example. This is due in part to the fact that dementias and other losses in brain function that sometimes accompany aging cause an obvious decline in the quality of life and these deficits are of more concern as the number of elderly increase. Stress also is a ubiquitous aspect of life and there is now a greater interest in understanding the role of stress and the stress response in brain aging. The key role of the hippocampus and its related brain structures in cognition, as well as in the feedback control of the response to stress, have made this brain area a logical focus of investigation for those interested in the impact of stress on brain aging. Here, we describe how the hippocampus changes with age and we examine the idea that age-related changes in the secretion patterns of the hypothalamic-pituitary adrenal (HPA) axis can contribute to aging of this structure. We also examine the proposal that stress, perhaps due to compromised HPA axis function, can contribute to hippocampal aging through exposure to excessive levels of glucocorticoids. The aging hippocampus does not appear to suffer a generalized loss of cells or synapses, although atrophy of the structure may occur in humans. Thus, age-related cognitive impairments are likely related to other neurobiological alterations that could include changes in the signaling, information encoding, plasticity, electrophysiological or neurochemical properties of neurons or glia. Although excessive levels of glucocorticoids are able to interfere with cognition, as well as hippocampal neuronal integrity, and aging is sometimes accompanied by an increase in these steroids because of inadequate feedback control of the HPA axis, none of these are a foregone consequence of aging. The general preservation of cells and the plastic potential of the hippocampus provide a focus for the development of pharmacological, nutritive or lifestyle strategies to combat age-related declines in the hippocampus as well as other brain areas.
随着岁月的流逝，许多身体系统（如内分泌、认知、运动系统）常常会出现功能丧失，但个体所表现出的功能受损程度存在很大差异。当前对大脑衰老的关注仍将持续，因为人口趋势表明平均寿命将持续增长。人们越来越重视了解衰老如何导致大脑功能衰退，认知能力下降就是一个主要例子。部分原因在于，痴呆症和其他有时伴随衰老出现的大脑功能丧失会导致生活质量明显下降，而且随着老年人数量的增加，这些缺陷更令人担忧。压力也是生活中普遍存在的一个方面，现在人们对了解压力及其应激反应在大脑衰老过程中的作用更感兴趣。海马体及其相关脑结构在认知以及应激反应的反馈控制中起着关键作用，这使得该脑区成为那些关注压力对大脑衰老影响的研究人员的一个合理研究重点。在此，我们描述海马体如何随年龄变化，并探讨下丘脑 - 垂体 - 肾上腺（HPA）轴分泌模式的年龄相关变化可能导致该结构衰老的观点。我们还研究了这样一种观点，即压力可能由于HPA轴功能受损，通过暴露于过量的糖皮质激素而导致海马体衰老。尽管在人类中可能会出现海马体结构萎缩，但衰老的海马体似乎并未普遍出现细胞或突触丧失。因此，与年龄相关的认知障碍可能与其他神经生物学改变有关，这些改变可能包括神经元或神经胶质细胞的信号传导、信息编码、可塑性、电生理或神经化学特性的变化。虽然过量的糖皮质激素能够干扰认知以及海马体神经元的完整性，并且由于HPA轴反馈控制不足，衰老有时会伴随着这些类固醇水平的升高，但这些都不是衰老的必然结果。海马体细胞的普遍保留及其可塑性为开发药理学、营养或生活方式策略提供了重点，以对抗海马体以及其他脑区与年龄相关的衰退。
