Gene-expression profile of the ageing brain in mice
Gene-expression profile of the ageing brain in mice
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DOI：
10.1038/77046
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发表时间：
2000-07-01
期刊：
影响因子：
30.8
通讯作者：
Prolla, TA
中科院分区：
文献类型：
--
作者：
Lee, CK;Weindruch, R;Prolla, TA
大脑老化导致认知和运动技能受损，是几种常见神经系统疾病（如阿尔茨海默病（AD）和帕金森病（PD））的主要风险因素。最近的研究表明，正常的大脑衰老与特定神经元回路中的细微形态和功能改变有关，而不是大规模的神经元损失。事实上，不同哺乳动物中枢神经系统的衰老有许多共同的特征，如锥体神经元萎缩、突触萎缩、纹状体多巴胺受体减少等。荧光色素积累、细胞骨架异常、反应性星形胶质细胞和小胶质细胞（2）。为了在分子水平上提供大脑衰老的第一个全球分析，我们使用代表6，347个基因的寡核苷酸阵列来确定小鼠衰老新皮层和小脑的基因表达谱。衰老导致的基因表达谱指示炎症反应，氧化应激和减少两个大脑区域的神经营养支持。在转录水平上，小鼠的大脑衰老与人类神经退行性疾病相似。热量限制，延缓哺乳动物的衰老过程，选择性地减弱了与年龄相关的炎症和应激反应基因的诱导。
Ageing of the brain leads to impairments in cognitive and motor skills, and is the major risk factor for several common neurological disorders such as Alzheimer disease (AD) and Parkinson disease (PD). Recent studies suggest that normal brain ageing is associated with subtle morphological and functional alterations in specific neuronal circuits, as opposed to large-scale neuronal loss'. In fact, ageing of the central nervous system in diverse mammalian species shares many features, such as atrophy of pyramidal neurons, synaptic atrophy, decrease of striatal dopamine receptors. accumulation of fluorescent pigments, cytoskeletal abnormalities, and reactive astrocytes and microglia(2). To provide the first global analysis of brain ageing at the molecular level, we used oligonucleotide arrays representing 6,347 genes to determine the gene-expression profile of the ageing neocortex and cerebellum in mice. Ageing resulted in a gene-expression profile indicative of an inflammatory response, oxidative stress and reduced neurotrophic support in both brain regions. At the transcriptional level, brain ageing in mice displays parallels with human neurodegenerative disorders. Caloric restriction, which retards the ageing process in mammals, selectively attenuated the age-associated induction of genes encoding inflammatory and stress responses.