Cited by 466Genetics, Aging, and Longevity in Model OrganismsGenomics and Chromatin DynamicsNF-κB Signaling Pathways

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

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Adler, Adam S., Sinha, Saurabh, Kawahara, Tiara L.A., Zhang, Jennifer Y., Segal, Eran, Chang, Howard Y.·2007·Genes & Development

Abstract

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-κB. Inducible genetic blockade of NF-κB 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-κB blockade and orthogonal cell cycle interventions revealed that NF-κB 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-κB is continually required to enforce many features of aging in a tissue-specific manner.

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  • NF-κB is the transcription factor most activated with aging.

    “Interestingly, NF-κB is the transcription factor that is most activated with aging (Adler et al., 2007).”

    From DNA damage-how and why we age? (2021) · cites this paper as Adler et al., 2007

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Authors
Adler, A. S., Sinha, S., Kawahara, T. L. A., Zhang, J. Y., Segal, E., & Chang, H. Y.
Affiliations
  • Stanford Medicine (US)
  • University of Illinois Urbana-Champaign (US)
  • Duke University (US)
  • Weizmann Institute of Science (IL)
Venue
Genes & Development
Published
2007-11-30
Volume
21
Issue
24
Pages
000.1-000
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2140323371
Cited by
466
References
43
Citations by year
2026: 12 · 2025: 16 · 2024: 16 · 2023: 26 · 2022: 26 · 2021: 25 · 2020: 17 · 2019: 25 · 2018: 27 · 2017: 23 · 2016: 26 · 2015: 38 · 2014: 25 · 2013: 32 · 2012: 36
Type
posted content
Language
en
Open access
Licence
other-oa
Locations
  • Genes & Development (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health and Human Services
  • American Cancer Society
  • Damon Runyon Cancer Research Foundation
  • California Breast Cancer Research Program
  • National Institutes of Health
  • National Cancer Institute
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (K01AR051470, K08AR050007)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
aging, NF-κB, cis-regulatory motifs, age-related gene expression, cell cycle exit, epidermis, tissue-specific aging, transcriptional regulation, gene expression signatures, human
MeSH terms
Aging, Amino Acid Sequence, Animals, Gene Expression Regulation, Humans, Immunohistochemistry, Molecular Sequence Data, Phenotype, NF-kappa B, Amino Acid Motifs, Electrophoretic Mobility Shift Assay, Mice

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