Mechanisms of Transcriptome Aging Figure 7. In silico inflammation profiles of aging in mouse skin and other tissues: Tail skin aging leads to decreased expression of genes associated with antigen-presenting cells. 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 mouse tail skin (CB6F1 strain) and other tissue types [31] (see Methods). This figure can be interpreted as described in the Figure 1 legend and is based upon the influence of aging on the expression of ‘‘signature transcripts’’ associated with different cell populations (listed in left margin). Red colors in the chart denote evidence for an age-related expansion or infiltration of the cell population type listed in each row (sees color scale and Figure 1 legend). The opposite trend is denoted by green colors (see color scale and Figure 1 legend). doi:10.1371/journal.pone.0033204.g007 decreased expression among (human) female subjects, but not males (Figures S5A and S5B). In mice, however, Zeb1 motif abundance was linked to age-increased expression in both males and females, contrasting strongly with the result obtained in human females (Figures S16A and S16B). Age-related shifts in estrogen dominance might contribute to the sex-specific Zeb1-expression association observed in humans. For instance, the gene encoding Zeb1 (Tcf8) is induced by estrogen and/or progesterone in chick oviduct, mouse uterus, human smooth muscle cells, and an osteosarcoma cell line, although these effects vary among estrogen- sensitive cell lines [52–54]. These Zeb1-mediated estrogen effects could impact skin aging phenotypes, since Zeb1 represses cellular senescence in mouse embryonic fibroblasts [55] and also represses the synthesis of Col1a1 in osteoblasts [56], Col1a2 in vascular smooth muscle cells [57], and both Col2a1 and Col11a2 in cartilage [58,59]. Mechanistic correspondence between senescent processes in humans and mice is an important issue in aging biology, since functional studies of individual genes and their influence on aging frequently use mice, and because mice are used to screen drugs PLoS ONE | www.plosone.org 10 March 2012 | Volume 7 | Issue 3 | e33204