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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Adler, AS; Sinha, S; Kawahara, TLA; Zhang, JY; Segal, E; Chang, HY

Published Date

  • December 15, 2007

Published In

Volume / Issue

  • 21 / 24

Start / End Page

  • 3244 - 3257

PubMed ID

  • 18055696

Pubmed Central ID

  • 18055696

International Standard Serial Number (ISSN)

  • 0890-9369

Digital Object Identifier (DOI)

  • 10.1101/gad.1588507

Language

  • eng

Conference Location

  • United States