Serial analysis of gene expression profiles of adult and aged mouse cerebellum.

Abstract Changes in specific cerebellar molecules contribute to impaired balance and motor coordination frequently observed in aged individuals. Serial analysis of gene expression (SAGE) was used to construct six libraries from adult and aged mouse cerebella. Combined unique tags for each group revealed 325 genes that were differentially expressed ( p -chance ≤ 0.05). Four additional tests (mixed effect model, t -test, Wilcoxon rank-sum and z -test) were used to reduce the likelihood of false positives. The first two tests accounted for intra-group variation, the third for outliers and the fourth was a probability test similar to p -chance. Twenty-nine genes were identified by at least two of the four tests as being differentially expressed in the aged cerebellum. Three of these genes are, as yet, unidentified and likely to represent novel genes involved in the cerebellar aging process. The largest group of genes revealed by the combined tests was related to glycerophospholipid metabolism, and included phosphoethanolamine, phosphatidic acid and diacylglycerol synthetic enzymes, suggesting that alterations in lipid biosynthesis may, at least in part, underlie changes in conductivity in the aged cerebellum.