Mechanisms of Transcriptome Aging Figure 3. Unsupervised clustering of gene expression signatures from humans and mice reveals that aging effects are predominantly species-specific. We generated gene expression profiles for aging in human and mouse skin and compared these with 25 aging profiles from human tissues and 28 aging profiles from mouse tissues. All human profiles (black labels) were generated based on data from the Affymetrix Human Genome U133 Plus 2.0 array platform and all mouse profiles (red labels) were generated based on data from the Affymetrix Mouse Genome 430 2.0 array platform (Tables S1 and S2). The cluster analysis is based upon a total of 3785 human-mouse transcript pairs, which collectively, were associated with 3646 unique human genes and 3580 unique mouse genes. All human-mouse transcript pairs were significantly altered by aging with respect to at least three separate human profiles or at least three separate mouse profiles (FDR-adjusted P,0.05). Heat map colors denote an adjusted fold-change ratio (old/young) in units of standard deviations to permit visual and quantitative comparison across tissues and species. In humans, adjusted ratios were obtained by calculating the estimated 40-year fold change (old/young) for each transcript and dividing this ratio by the standard deviation of all 3785 ratios calculated in a given profile (i.e., each row of the heatmap). Similarly, in mice, adjusted ratios were obtained by calculating the 2-year fold change (old/young) for each transcript and dividing this ratio by the standard deviation of all 3785 ratios calculated in a given profile (i.e., each row of the heatmap). Further details on the experimental datasets used to generate human and mouse aging profiles is provided in the Methods section, Table S1 and Table S2. doi:10.1371/journal.pone.0033204.g003 PLoS ONE | www.plosone.org 6 March 2012 | Volume 7 | Issue 3 | e33204