|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
24
|
|
pubmed:dateCreated |
2007-12-14
|
|
pubmed:databankReference |
|
|
pubmed:abstractText |
Aging is characterized by specific alterations in gene expression, but their underlying mechanisms and functional consequences are not well understood. Here we develop a systematic approach to identify combinatorial cis-regulatory motifs that drive age-dependent gene expression across different tissues and organisms. Integrated analysis of 365 microarrays spanning nine tissue types predicted fourteen motifs as major regulators of age-dependent gene expression in human and mouse. The motif most strongly associated with aging was that of the transcription factor NF-kappaB. Inducible genetic blockade of NF-kappaB for 2 wk in the epidermis of chronologically aged mice reverted the tissue characteristics and global gene expression programs to those of young mice. Age-specific NF-kappaB blockade and orthogonal cell cycle interventions revealed that NF-kappaB controls cell cycle exit and gene expression signature of aging in parallel but not sequential pathways. These results identify a conserved network of regulatory pathways underlying mammalian aging and show that NF-kappaB is continually required to enforce many features of aging in a tissue-specific manner.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-10896778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-11226216,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-11309499,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-11795524,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-12297622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-12520026,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-12673201,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-12736221,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-12845331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-12855472,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-14500985,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-14724177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-14730301,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-14744759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-14872484,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15004229,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15031306,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15044709,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15084260,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15152190,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15190254,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15308101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15371334,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15479644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15520862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15574883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15685170,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15699216,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15716955,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15734678,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-15920529,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-16048372,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-16183991,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-16199517,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-16449570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-16704453,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-1675604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-17086191,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-17520024,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-17707233,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18055696-7568133
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
0890-9369
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
21
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
3244-57
|
|
pubmed:dateRevised |
2011-3-29
|
|
pubmed:meshHeading |
pubmed-meshheading:18055696-Aging,
pubmed-meshheading:18055696-Amino Acid Motifs,
pubmed-meshheading:18055696-Amino Acid Sequence,
pubmed-meshheading:18055696-Animals,
pubmed-meshheading:18055696-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:18055696-Gene Expression Regulation,
pubmed-meshheading:18055696-Humans,
pubmed-meshheading:18055696-Immunohistochemistry,
pubmed-meshheading:18055696-Mice,
pubmed-meshheading:18055696-Molecular Sequence Data,
pubmed-meshheading:18055696-NF-kappa B,
pubmed-meshheading:18055696-Phenotype
|
|
pubmed:year |
2007
|
|
pubmed:articleTitle |
Motif module map reveals enforcement of aging by continual NF-kappaB activity.
|
|
pubmed:affiliation |
Program in Epithelial Biology and Cancer Biology Program, Stanford University School of Medicine, Stanford, California 94305, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
