SAGE in aging cerebellum

小脑的主要功能是整合感觉输入和运动输出，从而调节运动和平衡。小脑的衰老变化被认为会导致老年人中经常观察到的平衡和运动协调能力受损。小脑中与衰老相关的神经元特性变化以及由此产生的神经元损失已得到充分记录，并且已经描述了特定分子成分的功能或水平的改变。小脑衰老似乎是许多基因表达累积变化的结果。迄今为止，仅通过 DNA 微阵列检测了构成人类基因组的一小部分基因的衰老变化。 由于 DNA 微阵列技术是一个“封闭”系统，只能检测已知基因，因此我们建议使用 SAGE（基因表达系列分析）对成年和老年小鼠小脑中的基因表达进行全局分析。 SAGE 是一个“开放”系统，能够发现和数字量化已知和未知的基因。拟议的实验涉及 5 个月和 30 个月大小鼠小脑 SAGE 文库的构建、测序和生物信息学分析。由此产生的全面、定量的 SAGE 基因表达数据库，其中包括成年和老年小鼠小脑中的新基因，将通过 NCBI 网站传播。 未来的实验将研究热量限制对衰老小鼠小脑基因表达的影响，并全面表征其表达在衰老过程中发生显着改变的新基因。

The major function of the cerebellum is to integrate sensory input and motor output, thus modulating movement and balance. Senescent changes in the cerebellum are thought to contribute to the impairment in balance and motor coordination frequently observed in aged individuals. Aging-related changes in neuronal properties and resulting neuronal loss have been well documented in the cerebellum, and alterations in the function, or levels, of specific molecular components have been described. It is plausible that cerebellar senescence is the result of cumulative changes in the expression of many genes. To date only a fraction of the genes comprising the human genome have been assayed by DNA microarrays for senescent changes. Because DNA microarray technology is a "closed" system capable of detecting only known genes, we propose to conduct a global analysis of gene expression in the adult and aged mouse cerebellum using SAGE (Serial Analysis of Gene Expression). SAGE is an "open" system capable of discovering and digitally quantifying both known and, as yet, unknown genes. The proposed experiments involve the construction, sequencing and bioinformatic analysis of cerebellar SAGE libraries from a 5-month and 30-month old mouse. The resulting comprehensive and quantitative SAGE database of gene expression, which includes that of novel genes in the adult and aged mouse cerebellum, will be disseminated via the NCBI website. Future experiments will examine the effect of caloric restriction on gene expression in the aged mouse cerebellum, and a full characterization of novel genes whose expression is substantially altered during aging.