Transcriptional activation of Jun and Fos members of the AP‐1 complex is a conserved signature of immune aging that contributes to inflammaging
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Abstract
Diverse mouse strains have different health and life spans, mimicking the diversity among humans. To capture conserved aging signatures, we studied long‐lived C57BL/6J and short‐lived NZO/HILtJ mouse strains by profiling transcriptomes and epigenomes of immune cells from peripheral blood and the spleen from young and old mice. Transcriptional activation of the AP‐1 transcription factor complex, particularly Fos , Junb , and Jun genes, was the most significant and conserved aging signature across tissues and strains. ATAC‐seq data analyses showed that the chromatin around these genes was more accessible with age and there were significantly more binding sites for these TFs with age across all studied tissues, targeting pro‐inflammatory molecules including Il6 . Age‐related increases in binding sites of JUN and FOS factors were also conserved in human peripheral blood ATAC‐seq data. Single‐cell RNA‐seq data from the mouse aging cell atlas Tabula Muris Senis showed that the expression of these genes increased with age in B, T, NK cells, and macrophages, with macrophages from old mice expressing these molecules more abundantly than other cells. Functional data showed that upon myeloid cell activation via poly(I:C), the levels of JUN protein and its binding activity increased more significantly in spleen cells from old compared to young mice. In addition, upon activation, old cells produced more IL6 compared to young cells. In sum, we showed that the aging‐related transcriptional activation of Jun and Fos family members in AP‐1 complex is conserved across immune tissues and long‐ and short‐living mouse strains, possibly contributing to increased inflammation with age.
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Acute social defeat stress caused transcriptional activation of Fos, Junb, and Adcy4 and mild up-regulation of Socs1.
“The transcriptional activation of Fos, Junb, and Adcy4 facilitates GH transcription, while Socs1 mild up-regulation prevents GH overproduction”
From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [55]
The Results section (‘Transcriptional activation of Jun/Fos members’) reports activation of Fos and Junb with aging in immune cells, not following acute social defeat stress. The cited passages do not support the attributed changes in Adcy4 or Socs1, or the citing sentence’s claims about GH transcription and overproduction; searches for those terms found no relevant passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTranscriptional activation of Fos, Junb, and Adcy4 facilitates GH transcription, while Socs1 mild up-regulation prevents GH overproduction.
“The transcriptional activation of Fos, Junb, and Adcy4 facilitates GH transcription, while Socs1 mild up-regulation prevents GH overproduction”
From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [55]
The Results section reports age-related activation of Fos and Junb in immune cells. It does not link either gene to GH transcription, and searches for Adcy4, Socs1, growth hormone, and GH overproduction found no supporting passage in our copy. (LLM, conf=0.84)
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- Authors
- Karakaslar, E. O., Katiyar, N., Hasham, M., Youn, A., Sharma, S., Chung, C., Marches, R., Korstanje, R., Banchereau, J., & Ucar, D.
- Affiliations
- Leiden University Medical Center (NL)
- The Jackson Laboratory for Genomic Medicine (US)
- Jackson Laboratory (US)
- Sanofi (United States) (US)
- The Jackson Laboratory for Genomic Medicine Farmington Connecticut USA
- Immunai (United States) (US)
- Corresponding author
- Ucar, Duygu
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2023-02-24
- Volume
- 22
- Issue
- 4
- Pages
- e13792-e13792
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC10086525
- OpenAlex
- W4321996737
- Cited by
- 98
- References
- 77
- Citations by year
- 2026: 24 · 2025: 39 · 2024: 29 · 2023: 6
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion, cc-by)
- Funders
- American Federation for Aging Research
- Center for Strategic Scientific Initiatives, National Cancer Institute (P30CA034196)
- National Institute of General Medical Sciences (GM124922)
- National Institutes of Health (P30 AG038070, R01 AG052608, R01 AI142086, UH2 AG056925)
- 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 › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- immunosenescence, inflammaging, AP-1 transcription factor, c-Jun, FOS, JunB, transcriptional activation, chromatin accessibility, mouse strain differences, C57BL/6J mice, macrophages, B cells, T cells, natural killer cells, interleukin-6, myeloid cell activation, poly(I:C), epigenome, transcriptome
- MeSH terms
- Aging, Animals, Humans, Mice, Inbred C57BL, Transcriptional Activation, Interleukin-6, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-fos, Transcription Factor AP-1, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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