{
  "abstract": "Chromatin stability and nuclear architectural integrity constitute the primary defense against cellular senescence. Their collapse precipitates genomic disarray, epigenetic misregulation, and functional decline in stem cells. Although TOP2A is conventionally known for resolving DNA topological stress, its role in aging remains largely unexplored. Here, we found that TOP2A expression progressively decreased in senescent mesenchymal stem cells (MSCs), and its depletion initiated a catastrophic nuclear remodeling process characterized by the loss of Lamin B1, heterochromatin erosion, and senescence-associated phenotypes. Mechanistically, TOP2A directly regulated the expression of Lamin B1 to maintain nuclear architecture. TOP2A depletion set off a domino effect involving nuclear membrane rupture, loss of heterochromatin-associated factors (H3K9me3, KAP1, and LAP2), deterioration of cellular functions and acceleration of senescence. Notably, overexpression of TOP2A restored Lamin B1 levels, mitigated nuclear protein loss, preserved nuclear integrity, and counteracted cellular senescence. The in vivo relevance of these findings was further underscored by TOP2A inhibitor-induced brain aging in murine models. Our study establishes TOP2A as a novel modulator of cellular senescence, which stabilizes heterochromatin and nuclear structure, and provides new perspectives for targeting chromatin-based mechanisms in aging.",
  "abstract_shown": true,
  "affiliations": [
    "Stem Cell Research Center, Shantou University Medical College, Shantou, China.",
    "The Center for Reproductive Medicine, Shantou University Medical College, Shantou, China.",
    "Department of Gynecology, First Affiliated Hospital, Shantou University Medical College, Shantou, China.",
    "School of Basic Medicine, Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Guangdong Medical University, Dongguan, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ke Cheng"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yaru Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yueyuan Pan",
      "orcid": "0009-0000-5304-0194"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wenjun Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Denghong Yu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qi Zhou"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhiqian Zhong"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ruyi Mei"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Chaoliang Xu",
      "orcid": "0009-0008-9255-0603"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ayidana Hayierhan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yumei Ma"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yien Xu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qingdong Xie"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Pingnan Sun",
      "orcid": "0000-0002-3325-8062"
    },
    {
      "affs": [
        3
      ],
      "name": "Junzhi Zhou",
      "orcid": "0000-0002-0579-0916"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xiaoling Zhou",
      "orcid": "0000-0001-5721-944X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/epgcz2dv5mm62.bib",
  "cited_by": 0,
  "doi": "10.1111/acel.70787",
  "fulltext_url": "https://europepmc.org/articles/PMC13727716",
  "id": "epgcz2dv5mm62",
  "issns": [
    "1474-9718",
    "1474-9726"
  ],
  "landing_url": "https://europepmc.org/article/MED/42971918",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1312|Nuclear Structure and Function"
    ]
  ],
  "openalex": "W7225180562",
  "pdf_url": "https://europepmc.org/articles/PMC13727716?pdf=render",
  "pmcid": "PMC13727716",
  "pmid": "42971918",
  "published": "2026-11-01",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/epgcz2dv5mm62.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:43Z",
      "native_id": "MED:42971918",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42971918"
    },
    {
      "first_seen": "2026-11-06T12:23:32Z",
      "native_id": "PMC13727716",
      "source": "pmc",
      "url": "https://doi.org/10.1111/acel.70787"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Nuclear Structure and Function",
      "subfield": "molecular-biology"
    }
  ],
  "title": "TOP2A Maintains Heterochromatin Stability by Sustaining LMNB1 Expression to Counteract Senescence.",
  "title_text": "TOP2A Maintains Heterochromatin Stability by Sustaining LMNB1 Expression to Counteract Senescence.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:51Z",
  "url": "https://research.draconitic.com/paper/epgcz2dv5mm62",
  "venue": "Aging cell",
  "versions": []
}