Mechanisms of Transcriptome Aging Figure 1. In silico inflammation profiles of aging in human tissues: Sex-specific lymphocyte signatures in skin. An algorithm for calculation of inflammation profiles based on microarray data was used to establish a gene expression-based mapping of inflammation events associated with aging in human skin and other tissue types (see Methods section and Figure 2 from Swindell et al. [31]). Colors reflect age-associated gene expression patterns among ‘‘signature transcripts’’ that exhibit elevated expression in different cell populations (listed in left margin). Dark red colors indicate cases in which signature transcripts for a given cell population increase with age (i.e., the ratio of age-increased to age-decreased signature transcripts is greater than one). Filled black circles indicate significant bias towards age-increased expression among signature transcripts (FDR-adjusted P,0.05; Fisher’s exact test), suggesting increased abundance or infiltration of that cell population with aging. The opposite pattern, in which signature transcripts are disproportionately decreased with age, is indicated by green squares within the chart (indicative of decreased cell type abundance with age). For most cell population categories (rows), data from multiple cell populations was available, which permitted calculation of several signature transcript ratios (r1, r2…rn). In these cases, the maximum ratio is displayed in the chart if the median value of r1, r2… rn is greater than 0.50 (since, in this case, most evidence suggests bias towards age-increased expression among the n replicate sets of signature transcripts). The minimum ratio is displayed if the median value of r1, r2… rn is less than 0.50 (since, in this case, most evidence suggests bias towards age-decreased expression among the n replicate sets of signature transcripts). doi:10.1371/journal.pone.0033204.g001 Zeb1, AP-2 and YY1 motifs have female-specific associations with the expression profile of intrinsic human skin aging The intracellular expression response to aging is coordinated, in part, by the activation or repression of transcription by sequence- specific transcription factors [8,19,27]. To identify candidate transcriptional regulators in aging skin, we assembled a dictionary of 541 DNA binding site motifs for mammalian transcription factors from the UniPROBE and Jaspar databases [32–34], and investigated whether abundance of each individual motif within 2 kb upstream and 200 bp downstream of transcription start sites was associated with increased or decreased expression with age PLoS ONE | www.plosone.org 3 March 2012 | Volume 7 | Issue 3 | e33204