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导致老年人经常观察到的平衡和运动协调障碍的原因。在小脑中已经充分记录了神经元特性的衰老相关变化和导致的神经元损失，并且已经描述了特定分子组分的功能或水平的改变。小脑衰老是许多基因表达累积变化的结果，这似乎是合理的。迄今为止，只有一小部分的基因组成的人类基因组已被测定的DNA微阵列的衰老变化。 由于DNA微阵列技术是一个“封闭”的系统，能够检测只有已知的基因，我们建议进行全球分析的基因表达在成年和老年小鼠小脑使用SAGE（基因表达系列分析）。SAGE是一个“开放”的系统，能够发现和数字量化已知和未知的基因。所提出的实验涉及来自5个月和30个月大的小鼠的小脑SAGE文库的构建、测序和生物信息学分析。由此产生的基因表达的全面和定量SAGE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老年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实质性变化的新基因。

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.