Meta-Profiles of Gene Expression during Aging Limited Similarities between Mouse and Human and an Unexpectedly Decreased Inflammatory Signature 英文参考文献.docVIP

Meta-ProfilesofGeneExpressionduringAging:Limited SimilaritiesbetweenMouseandHumanandan UnexpectedlyDecreasedInflammatorySignature WilliamR.Swindell1*,AndrewJohnston2,LiouSun3,XianyingXing2,GaryJ.Fisher2,MarthaL.Bulyk4,5,6, JamesT.Elder2,JohannE.Gudjonsson2 1Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America, 2Department of Dermatology, University of Michigan Medical School,AnnArbor,Michigan,UnitedStatesofAmerica,3DepartmentofPathology,UniversityofMichiganMedicalSchool,AnnArbor,Michigan,UnitedStatesofAmerica, 4Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 5DepartmentofPathology,BrighamandWomen’sHospitalandHarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica,6DivisionofHealthSciences andTechnology,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica 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 alarge-scale shift in geneexpression,butunderlyingmechanismsarenotunderstoodandconservationofthesemechanismsbetweenhumans andmiceisuncertain. Results: We used genome-wide expression profiling to investigate the aging skin transcriptome. In humans, age-related shiftsingeneexpressionweresex-specific.Infemales,agingincreasedexpressionoftranscriptsassociatedwithT-cells,B- cellsanddendriticcells,anddecreasedexpressionofgenesinregionswithelevatedZeb1,AP-2andYY1motifdensity.In males,however, theseeffects werecontrasting orabsent. Whenage-associatedgene expressionpatterns inhuman skin were compared to those in tail skin from CB6F1 mice, overall human-mouse correspondence was weak. Moreover, inflammatorygeneexpressionpatternswerenotinducedwithagingofmousetailskin,andwell-knownagingbiomarkers wereinfactdecreased(e.g.,Clec7a,Lyz1andLyz2).