{
  "abstract": "Aging is the major risk factor for neurodegenerative disease, yet the mechanisms linking physiological aging to brain dysfunction remain unclear. We investigated the brains of telomere-shortened mice and observed lipofuscinosis, hypomyelination, microglial atrophy, and cognitive deficits. Single-nucleus RNA sequencing (snRNA-seq) revealed accelerated glial aging and elevated microglial senescence pathways. In a senescence model of human induced pluripotent stem cell (iPSC)-derived microglia, delta-like non-canonical Notch ligand 1 (DLK1) was identified as a novel senescence-associated ligand. Soluble DLK1 (sDLK1) was increased in the cerebrospinal fluid of telomere-shortened and naturally aged mice, and this increase was eliminated by microglial depletion. In vivo elevation of sDLK1 caused hypomyelination and blocked oligodendrocyte lineage progression, and these effects demonstrate the detrimental nature of excessive sDLK1. In human iPSC systems, sDLK1 impaired oligodendrocyte maturation and altered calcium signaling in excitatory neurons. These findings identify microglial senescence as a core consequence of telomere shortening and reveal sDLK1 as a microglia-derived senescence ligand that drives oligodendrocyte and neuronal dysfunction in aging.",
  "abstract_shown": true,
  "affiliations": [
    "Helen and Robert Appel Institute for Alzheimer’s Disease Research, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA",
    "Neuroscience Graduate Program, Weill Cornell Medicine, New York, NY, 10065, USA",
    "Gladstone Institutes, San Francisco, CA, 94158, USA",
    "Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA",
    "Lead contact"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Bangyan Liu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Matthew Mahoney"
    },
    {
      "affs": [
        0
      ],
      "name": "Yilin Feng"
    },
    {
      "affs": [
        2
      ],
      "name": "Maria Telpoukhovskaia"
    },
    {
      "affs": [
        0
      ],
      "name": "Alice Maria Giani"
    },
    {
      "affs": [
        0
      ],
      "name": "Eileen Ruth Torres"
    },
    {
      "affs": [
        2
      ],
      "name": "Lihong Zhan"
    },
    {
      "affs": [
        0
      ],
      "name": "Pearly Ye"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingjie Zhu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nessa R Foxe"
    },
    {
      "affs": [
        0
      ],
      "name": "Daphne Zhu"
    },
    {
      "affs": [
        3
      ],
      "name": "Xinran Tong"
    },
    {
      "affs": [
        2
      ],
      "name": "Deepak Srivastava"
    },
    {
      "affs": [
        2
      ],
      "name": "Christina V. Theodoris"
    },
    {
      "affs": [
        0
      ],
      "name": "Shiaoching Gong"
    },
    {
      "affs": [
        0
      ],
      "name": "Mingrui Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Fan"
    },
    {
      "affs": [
        0,
        1,
        4
      ],
      "name": "Li Gan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6smh2xyhb6c5y.bib",
  "cited_by": 0,
  "doi": "10.1016/j.neuron.2026.07.021",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733302/",
  "id": "6smh2xyhb6c5y",
  "issns": [
    "0896-6273",
    "1097-4199"
  ],
  "landing_url": "https://doi.org/10.1016/j.neuron.2026.07.021",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W7202213818",
  "pdf_url": null,
  "pmcid": "PMC13733302",
  "pmid": "42580340",
  "published": "2026-08-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6smh2xyhb6c5y.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:07Z",
      "native_id": "PMC13733302",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.neuron.2026.07.021"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Neuroinflammation and Neurodegeneration Mechanisms",
      "subfield": "neurology"
    }
  ],
  "title": "Senescent microglia with shortened telomeres secrete soluble DLK1 to induce aging-associated hypomyelination and neuronal dysfunction",
  "title_text": "Senescent microglia with shortened telomeres secrete soluble DLK1 to induce aging-associated hypomyelination and neuronal dysfunction",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:07Z",
  "url": "https://research.draconitic.com/paper/6smh2xyhb6c5y",
  "venue": "Neuron",
  "versions": []
}