| First Author | Adler AS | Year | 2007 |
| Journal | Genes Dev | Volume | 21 |
| Issue | 24 | Pages | 3244-57 |
| PubMed ID | 18055696 | Mgi Jnum | J:128484 |
| Mgi Id | MGI:3767336 | Doi | 10.1101/gad.1588507 |
| Citation | Adler AS, et al. (2007) Motif module map reveals enforcement of aging by continual NF-{kappa}B activity. Genes Dev 21(24):3244-57 |
| 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. |
