for 24 month- vs. 6 month-old mice samples. Percentile ranks of these expression fold changes relative to expression changes of all 8932 genes assayed in each tissue are shown. (a) Genes predicted to be targeted by seq_735943_x3. (b) Genes predicted to be targeted by 14 novel downregulated miRNAs. Yellow: genes demonstrating expression fold change falling in the top or bottom 5th percentile of all gene expression changes. Green: gene demonstrating significant expression change in 24 month- vs. 6 month-old animals (P-value ,0.05, Welch’s two sample t-test). Red: gene also found in Lee et al. [6] as demonstrating increased expression with age in the neocortex (1.8-fold increase in 30- vs. 5- month old mice). Of the 43 insulin signaling pathway genes predicted to be targeted by downregulated novel miRNAs, 11 References 1. Yankner BA, Lu T, Loerch P (2008) The aging brain. Annu Rev Pathol 3: 41– 66. 2. Obeso JA, Rodriguez-Oroz MC, Goetz CG, Marin C, Kordower JH, et al. 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