{
  "abstract": "Age-related cognitive decline is associated with altered physiology of the hippocampus. While changes in gene expression have been observed in aging brain, the regulatory mechanisms underlying these changes remain underexplored. We generated single-nucleus gene expression, chromatin accessibility, DNA methylation, and 3D genome data from 40 human hippocampal tissues spanning adult lifespan. We observed a striking loss of astrocytes, OPC, and endothelial cells during aging, including astrocytes that play a role in regulating synapses. Microglia undergo a dramatic switch from a homeostatic state to a primed inflammatory state through DNA methylome and 3D genome reprogramming. Aged cells experience erosion of their 3D genome architecture. Our study identifies age-associated changes in cell types/states and gene regulatory features that provide insight into cognitive decline during human aging.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA",
    "Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA",
    "University of California, San Diego",
    "Department of Anatomy and Neurobiology, University of California, Irvine School of Medicine, Irvine, CA, USA",
    "Immunis Inc., Irvine, CA, USA",
    "University of California, Irvine",
    "Department of Biochemistry and Molecular Medicine and the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA",
    "Washington University, St Louis",
    "Department of Genetics, The Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA",
    "McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA",
    "Arc Institute, Palo Alto, CA, USA",
    "Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA",
    "Univ. of California San Diego",
    "Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA, USA",
    "Department of Medicine, University of California, School of Medicine, La Jolla, CA, USA",
    "Department of Neurobiology and Behavior, University of California, Irvine, CA, USA",
    "Department of Neurology, University of California, Irvine School of Medicine, Irvine, CA, USA",
    "The Center for Neural Circuit Mapping, University of California, Irvine, CA, USA",
    "New York Genome Center, New York, NY, USA",
    "Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Nathan R. Zemke",
      "orcid": "0000-0002-6326-5925"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Seo Yeon Lee",
      "orcid": "0000-0003-2585-7863"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Sainath Mamde"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Bing Yang",
      "orcid": "0000-0001-6739-2932"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Nicole C. Berchtold"
    },
    {
      "affs": [
        3,
        5
      ],
      "name": "B. Maximiliano Garduño",
      "orcid": "0000-0001-8828-0614"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Hannah S. Indralingam",
      "orcid": "0009-0000-1790-109X"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Weronika M. Bartosik",
      "orcid": "0009-0007-7724-5216"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Pik Ki Lau",
      "orcid": "0009-0005-4405-9746"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Keyi Dong",
      "orcid": "0009-0009-8662-4706"
    },
    {
      "affs": [
        0,
        6,
        2
      ],
      "name": "Emily Hsu",
      "orcid": "0000-0001-5096-0745"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Amanda Yang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Yasmine Tani"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Chumo Chen",
      "orcid": "0009-0004-3203-4712"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Qiurui Zeng"
    },
    {
      "affs": [
        3,
        5
      ],
      "name": "Varun Ajith"
    },
    {
      "affs": [
        3,
        7
      ],
      "name": "Liqi Tong",
      "orcid": "0000-0001-9470-5885"
    },
    {
      "affs": [
        8,
        7
      ],
      "name": "Chanrung Seng",
      "orcid": "0009-0003-5671-917X"
    },
    {
      "affs": [
        8,
        7
      ],
      "name": "Daofeng Li",
      "orcid": "0000-0001-7492-3703"
    },
    {
      "affs": [
        8,
        9,
        5
      ],
      "name": "Ting Wang",
      "orcid": "0000-0002-6800-242X"
    },
    {
      "affs": [
        10,
        11,
        12
      ],
      "name": "Jingtian Zhou",
      "orcid": "0000-0003-2060-1922"
    },
    {
      "affs": [
        11,
        13
      ],
      "name": "Joseph R. Ecker",
      "orcid": "0000-0001-5799-5895"
    },
    {
      "affs": [
        1,
        14
      ],
      "name": "Christopher K. Glass",
      "orcid": "0000-0003-4344-3592"
    },
    {
      "affs": [
        15,
        16
      ],
      "name": "Carl W. Cotman",
      "orcid": "0000-0001-6533-9062"
    },
    {
      "affs": [
        3,
        17
      ],
      "name": "Xiangmin Xu",
      "orcid": "0000-0002-5828-1533"
    },
    {
      "affs": [
        1,
        18,
        19
      ],
      "name": "Bing Ren",
      "orcid": "0000-0002-5435-1127"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/37437bsb5wqr5.bib",
  "cited_by": 28,
  "doi": "10.1126/science.adt8307",
  "fulltext_url": null,
  "id": "37437bsb5wqr5",
  "issns": [
    "0036-8075",
    "0193-4511",
    "1095-9203"
  ],
  "landing_url": "https://doi.org/10.1126/science.adt8307",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "1312|Single-cell and spatial transcriptomics"
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  "pdf_url": null,
  "pmcid": "PMC11507755",
  "pmid": "39463924",
  "published": "2026-07-23",
  "publisher": "American Association for the Advancement of Science",
  "ris": "https://research.draconitic.com/paper/37437bsb5wqr5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
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      "url": "https://doi.org/10.1126/science.adt8307"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
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  ],
  "title": "Epigenetic and 3D genome reprogramming during the aging of the human hippocampus",
  "title_text": "Epigenetic and 3D genome reprogramming during the aging of the human hippocampus",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:05Z",
  "url": "https://research.draconitic.com/paper/37437bsb5wqr5",
  "venue": "Science",
  "versions": []
}