{
  "abstract": "As age is a significant risk factor for multiple neurodegenerative diseases, investigating normal brain aging may help identify molecular events contributing to increased disease risk over time. Single-nucleus RNA sequencing (snRNA-seq) enables analysis of gene expression changes within specific cell-types, offering insights into the molecular mechanisms underlying aging. However, most brain aging snRNA-seq datasets use age-matched controls from studies focused on pathology and sample cortical regions. Therefore, there is a need to investigate non-pathological aging within brain regions vulnerable to age-related diseases. We report a snRNA-seq study of 6 young (20-30 years) and 7 aged (60-85 years) individuals encompassing four different brain regions: the entorhinal cortex, middle temporal gyrus, subventricular zone, and putamen. We captured over 150,000 nuclei representing 10 broad cell-types. Region- and cell-type-specific differential expression analyses identified over 8000 age-associated genes. Notably, within a given cell-type, most of these associations were region-specific. Functional enrichment analyses of gene sets for each cell-type-region subgroup reflected multiple hallmarks of aging, including: proteostasis, interactions with cytokines, vesicular trafficking, metabolism, inflammation, metal ion homeostasis, and cellular senescence. Overall, our findings suggest that unique cell-types exhibit distinct transcriptional aging profiles both at the cell-type level and across different brain regions.",
  "abstract_shown": true,
  "affiliations": [
    "Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA",
    "Computational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA",
    "DataTecnica LLC, Washington, DC, USA",
    "Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA",
    "Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA",
    "Neurodegenerative Diseases Research Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA",
    "Human Brain Collection Core, Division of Intramural Research, National Institute of Mental Health, NIH, Bethesda, MD, USA",
    "Computational and Evolutionary Neurogenomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA",
    "Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. cookson@mail.nih.gov",
    "Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA. cookson@mail.nih.gov"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Monica E. Mesecar",
      "orcid": "0000-0001-6843-9501"
    },
    {
      "affs": [
        0
      ],
      "name": "Megan F. Duffy",
      "orcid": "0000-0003-0094-0900"
    },
    {
      "affs": [
        0
      ],
      "name": "Dominic J. Acri",
      "orcid": "0000-0003-1942-0892"
    },
    {
      "affs": [
        1
      ],
      "name": "Jinhui Ding",
      "orcid": "0000-0002-4691-4524"
    },
    {
      "affs": [
        0
      ],
      "name": "Rebekah G. Langston",
      "orcid": "0000-0003-0123-7934"
    },
    {
      "affs": [
        2
      ],
      "name": "Syed I. Shah"
    },
    {
      "affs": [
        3,
        2
      ],
      "name": "Mike A. Nalls",
      "orcid": "0000-0003-0319-4325"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Xylena Reed",
      "orcid": "0000-0002-7563-9365"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Sonja W. Scholz",
      "orcid": "0000-0002-6623-0429"
    },
    {
      "affs": [
        0
      ],
      "name": "D. Thad Whitaker"
    },
    {
      "affs": [
        6
      ],
      "name": "Pavan Kumar Auluck",
      "orcid": "0000-0003-4799-7904"
    },
    {
      "affs": [
        6
      ],
      "name": "Stefano Marenco",
      "orcid": "0000-0002-2488-2365"
    },
    {
      "affs": [
        7
      ],
      "name": "Alex R. DeCasien",
      "orcid": "0000-0002-6205-5408"
    },
    {
      "affs": [
        1
      ],
      "name": "Jesse Raphael Gibbs",
      "orcid": "0000-0002-6985-0658"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Mark Cookson",
      "orcid": "0000-0002-1058-3831"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5j18bkkxa4y6y.bib",
  "cited_by": 27,
  "doi": "10.1038/s41514-026-00391-9",
  "fulltext_url": null,
  "id": "5j18bkkxa4y6y",
  "issns": [
    "2731-6068"
  ],
  "landing_url": "https://doi.org/10.1038/s41514-026-00391-9",
  "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": [
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
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  "pdf_url": "https://www.nature.com/articles/s41514-026-00391-9_reference.pdf",
  "pmcid": "PMC10418086",
  "pmid": "37577533",
  "published": "2026-05-13",
  "publisher": "Springer Science+Business Media",
  "ris": "https://research.draconitic.com/paper/5j18bkkxa4y6y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W7161064970",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41514-026-00391-9"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Region-specific transcriptional signatures of brain aging in the absence of neuropathology at the single-cell level",
  "title_text": "Region-specific transcriptional signatures of brain aging in the absence of neuropathology at the single-cell level",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:05Z",
  "url": "https://research.draconitic.com/paper/5j18bkkxa4y6y",
  "venue": "npj Aging",
  "versions": []
}