{
  "abstract": "Brain aging is associated with chronic, low-grade inflammation known as inflammaging, which is largely driven by senescent glial cells secreting pro-inflammatory factors termed as senescence-associated secretory phenotype (SASP). In humans, the release of SASP factors in the brain is linked with an increased risk for the development of neurodegenerative disorders; thus, elucidating the underlying molecular mechanisms is essential for understanding the pathophysiology of brain aging. Both NF-κB and Notch signaling are known to regulate SASP expression; however, their mode of interaction in brain inflammaging is poorly understood. Here, we demonstrate that brain aging is broadly associated with NF-κB activation but Notch suppression using different transgenic mouse models. Astrocytic NF-κB activation in young mice was able to mimic premature SASP formation but repressed Notch signaling in parallel. Bioinformatic analyses further identified conserved crosstalk sites within SASP genes co-occupied by Notch/RBPJ and NF-κB transcription factors in vivo, allowing specific combinatorial regulation. Importantly, selective physical interactions enable that activated Notch can act as a negative modulator of NF-κB signaling at different molecular levels. Consistently, pharmacological activation of Notch in primary astrocytes significantly reduced NF-κB-driven SASP gene expression. Together, these findings identify Notch–NF-κB crosstalk as a potential therapeutic target to mitigate brain inflammaging.",
  "abstract_shown": true,
  "affiliations": [
    "University Hospital Ulm, Department of Internal Medicine I , Albert-Einstein-Allee 23, 89081 Ulm ,",
    "Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University , Suzhou 215002 ,",
    "University of Ulm, Institute for Physiological Chemistry , Albert-Einstein-Allee 11, 89081 Ulm ,",
    "Justus-Liebig-University Giessen, Institute of Biochemistry , Friedrichstrasse 24, 35392 Giessen ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Qingwen Yang",
      "orcid": "0000-0002-9746-8317"
    },
    {
      "affs": [
        0
      ],
      "name": "Hina Zarrin",
      "orcid": "0009-0007-2945-104X"
    },
    {
      "affs": [
        2
      ],
      "name": "Tabea Hein",
      "orcid": "0009-0000-4592-984X"
    },
    {
      "affs": [
        0
      ],
      "name": "Burak Yildiz"
    },
    {
      "affs": [
        2
      ],
      "name": "Vivien Prex"
    },
    {
      "affs": [
        2
      ],
      "name": "Konstantinos Siontas"
    },
    {
      "affs": [
        3
      ],
      "name": "Tilman Borggrefe",
      "orcid": "0000-0003-4325-5452"
    },
    {
      "affs": [
        3
      ],
      "name": "Benedetto Daniele Giaimo",
      "orcid": "0000-0003-0384-325X"
    },
    {
      "affs": [
        3
      ],
      "name": "Tobias Friedrich"
    },
    {
      "affs": [
        3
      ],
      "name": "M Lienhard Schmitz",
      "orcid": "0000-0002-6984-7192"
    },
    {
      "affs": [
        2
      ],
      "name": "Thomas Wirth"
    },
    {
      "affs": [
        0
      ],
      "name": "Franz Oswald",
      "orcid": "0000-0002-2923-5765"
    },
    {
      "affs": [
        2
      ],
      "name": "Bernd Baumann",
      "orcid": "0000-0003-4327-811X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7pjmjagvwaz7v.bib",
  "cited_by": 0,
  "doi": "10.1093/nar/gkag1110",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736121/",
  "id": "7pjmjagvwaz7v",
  "issns": [
    "0305-1048",
    "1362-4962"
  ],
  "landing_url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1110/9013032",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/SCI00010"
    ],
    [
      "heading",
      "Gene regulation, Chromatin and Epigenetics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://academic.oup.com/nar/article-pdf/54/20/gkag1110/73097578/gkag1110.pdf",
  "pmcid": "PMC13736121",
  "pmid": "42985778",
  "published": "2026-11-05",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/7pjmjagvwaz7v.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:20:58Z",
      "native_id": "10.1093/nar/gkag1110",
      "source": "crossref",
      "url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1110/9013032"
    },
    {
      "first_seen": "2026-11-09T12:21:39Z",
      "native_id": "PMC13736121",
      "source": "pmc",
      "url": "https://doi.org/10.1093/nar/gkag1110"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:0305-1048",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Notch/NF-κB crosstalk signaling controls SASP gene expression during brain aging",
  "title_text": "Notch/NF-κB crosstalk signaling controls SASP gene expression during brain aging",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:39Z",
  "url": "https://research.draconitic.com/paper/7pjmjagvwaz7v",
  "venue": "Nucleic Acids Research",
  "versions": []
}