SAGE in aging cerebellum

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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.