title: Meta-profiles of gene expression during aging: limited similarities between mouse and human and an unexpectedly decreased inflammatory signature.
abstract: BACKGROUND
  Skin aging is associated with intrinsic processes that compromise the structure of the extracellular matrix while promoting loss of functional and regenerative capacity. These processes are accompanied by a large-scale shift in gene expression, but underlying mechanisms are not understood and conservation of these mechanisms between humans and mice is uncertain.
  
  
  RESULTS
  We used genome-wide expression profiling to investigate the aging skin transcriptome. In humans, age-related shifts in gene expression were sex-specific. In females, aging increased expression of transcripts associated with T-cells, B-cells and dendritic cells, and decreased expression of genes in regions with elevated Zeb1, AP-2 and YY1 motif density. In males, however, these effects were contrasting or absent. When age-associated gene expression patterns in human skin were compared to those in tail skin from CB6F1 mice, overall human-mouse correspondence was weak. Moreover, inflammatory gene expression patterns were not induced with aging of mouse tail skin, and well-known aging biomarkers were in fact decreased (e.g., Clec7a, Lyz1 and Lyz2). These unexpected patterns and weak human-mouse correspondence may be due to decreased abundance of antigen presenting cells in mouse tail skin with age.
  
  
  CONCLUSIONS
  Aging is generally associated with a pro-inflammatory state, but we have identified an exception to this pattern with aging of CB6F1 mouse tail skin. Aging therefore does not uniformly heighten inflammatory status across all mouse tissues. Furthermore, we identified both intercellular and intracellular mechanisms of transcriptome aging, including those that are sex- and species-specific.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America. wswindell@genetics.med.harvard.edu
authors.forename: William R
authors.initials: WR
authors.lastname: Swindell
authors.forename: Andrew
authors.initials: A
authors.lastname: Johnston
authors.forename: Liou
authors.initials: L
authors.lastname: Sun
authors.forename: Xianying
authors.initials: X
authors.lastname: Xing
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Fisher
authors.forename: Martha L
authors.initials: ML
authors.lastname: Bulyk
authors.forename: James T
authors.initials: JT
authors.lastname: Elder
authors.forename: Johann E
authors.initials: JE
authors.lastname: Gudjonsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016000:Cluster Analysis; D051152:Clusterin / Q000235:genetics; D003872:Dermatitis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D059372:Nucleotide Motifs; D012737:Sex Factors; D015595:Skin Aging / Q000235:genetics; D013045:Species Specificity; D050656:Transcription Factor AP-2 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome; D050986:YY1 Transcription Factor / Q000235:genetics; D055815:Young Adult; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D051152:Clusterin; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; C115469:Prrx2 protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C486307:ZEB1 protein, human; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1