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是老年人经常观察到的平衡和运动协调能力受损的原因之一。在小脑中，与衰老相关的神经元特性的变化和由此导致的神经元丢失已经被很好地记录下来，并且特定分子成分的功能或水平的变化已经被描述。看来，小脑衰老是许多基因表达累积变化的结果。到目前为止，只有一小部分组成人类基因组的基因被DNA微阵列检测到了衰老变化。 由于DNA微阵列技术是一个封闭的系统，只能检测已知的基因，我们建议使用SAGE(基因表达序列分析)对成年和老年小鼠小脑的基因表达进行全局分析。SAGE是一个“开放”的系统，能够发现已知和未知的基因，并对其进行数字量化。所提出的实验涉及5月龄和30月龄小鼠小脑SAGE文库的构建、测序和生物信息学分析。由此产生的全面和定量的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网站发布。 未来的实验将检验卡路里限制对衰老小鼠小脑基因表达的影响，并全面描述在衰老过程中表达显著改变的新基因。

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.