Unknown,Transcriptomics,Genomics,Proteomics

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Role of NF-kB in aging

ABSTRACT: To address the role of NF-kB in aging in vivo, we utilized a well-characterized system that allows inducible and site-specific inhibition of NF-kB activity in murine skin. The hormone binding domain of the mutant estrogen receptor that is responsive to 4-hydroxytamoxifen (4-OHT) was fused to a mutant of p50 (IDNkB, inducible dominant negative NF-kB) that dimerizes with other NF-kB subunits but is unable to bind DNA, thus dominantly inhibiting NF-kB activity. Expression was driven within the basal layer of murine epidermis by the keratin 14 promoter in transgenic mice. To test whether NF-kB activity is required to maintain age-associated gene expression, we applied topical 4-OHT and ethanol vehicle (EtOH) for two weeks to the right (R) and left (L) dorsal flanks, respectively, of chronologically aged transgenic mice (O, 18-23 months). Young transgenic mice (Y, 1 month) were treated in parallel as control. Skin samples were harvested and analyzed for gene expression using mouse cDNA microarrays containing 35,217 elements, representing 18,880 unique genes. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set Computed

ORGANISM(S): Mus musculus

SUBMITTER: Adam Adler

PROVIDER: E-GEOD-3845 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Motif module map reveals enforcement of aging by continual NF-kappaB activity.

Adler Adam S AS Sinha Saurabh S Kawahara Tiara L A TL Zhang Jennifer Y JY Segal Eran E Chang Howard Y HY

Genes & development 20071130 24

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 s ...[more]

PMID: 18055696

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Role of NF-kB in aging

Publications

Motif module map reveals enforcement of aging by continual NF-kappaB activity.

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