Motif module map reveals enforcement of aging by continual NF-κB activity
Open accessAbstract
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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Cheng, H. S., Njock, M.-S., Khyzha, N., Dang, L. T., & Fish, J. E. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00422 · Cited by 69 · see citing works
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Ribeiro, J. D., Morey, L., Mas, A., Gutierrez, A., Luis, N. M., Mejetta, S., Richly, H., Benitah, S. A., Keyes, W. M., & Di Croce, L. (2013) · Oncogene · doi:10.1038/onc.2012.241 · Cited by 41 · see citing works
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Brett, J. O., & Rando, T. A. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.05.004 · Cited by 12 · see citing works
- 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
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2007-11-30
- Volume
- 21
- Issue
- 24
- Pages
- 000.1-000
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2113026
- 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
- hybrid
- doi.org
- 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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