OSCR

TOP2A Maintains Heterochromatin Stability by Sustaining LMNB1 Expression to Counteract Senescence.

Overview

Authors: Ke Cheng1,2, Yaru Wang1,2, Yueyuan Pan1,2, Wenjun Zhang1,2, Denghong Yu1,2, Qi Zhou1,2, Zhiqian Zhong1,2, Ruyi Mei1,2, Chaoliang Xu1,2, Ayidana Hayierhan1,2, Yumei Ma1,2, Yien Xu1,2, Qingdong Xie1,2, Pingnan Sun1,2,3, Junzhi Zhou4, Xiaoling Zhou1,2,3
ORCID iDs: Yueyuan Pan, Chaoliang Xu, Pingnan Sun, Junzhi Zhou, Xiaoling Zhou
  1. Stem Cell Research Center Shantou University Medical College Shantou China
  2. The Center for Reproductive Medicine Shantou University Medical College Shantou China
  3. Department of Gynecology First Affiliated Hospital, Shantou University Medical College Shantou China
  4. School of Basic Medicine, Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics Guangdong Medical University Dongguan China
Institutions: Shantou University (China); Shantou University Medical College (China); First Affiliated Hospital of Shantou University Medical College (China); Guangdong Medical College (China)
Journal: Aging cell, volume 25, issue 11, article e70787
Dates: received 2 November 2025; accepted 20 October 2026; published online 2 November 2026; in print November 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1111/acel.70787 · PMID 42971918 · PMCID PMC13727716 · OpenAlex W7225180562
Open access: gold, a free copy (OpenAlex)
Status: data only (how the code is found and verified)
Categories: human (organism), mouse (organism), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions
Keywords: aging, heterochromatin, LMNB1, TOP2A
MeSH: Cellular Senescence*, DNA Topoisomerases, Type II*, Heterochromatin*, Lamin Type B*, Poly-ADP-Ribose Binding Proteins*, Animals, Humans, Mesenchymal Stem Cells, Mice (* major topic)
Topic: Nuclear Structure and Function (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Natural Science Foundation of China (81571994, 81870432, 81570567, 82372916); Basic and Applied Basic Research Foundation of Guangdong Province (2023A1515010449, 2025A1515010366, 2023A1515010660, 2024A1515010341); Li Ka Shing Foundation (L1111 2008); Natural Science Foundation of Guangdong Province (2024A1515140168)
Citations: not cited yet (Europe PMC); 114 references in the paper

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data and to no code of its authors: see the Data section.

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Data

Datasets cited

Data Availability Statement

The data that supports the findings of this study are available in the Supporting Information of this article. The data that support the findings of this study are available in Genome Sequence Archive, GSA at https://ngdc.cncb.ac.cn/gsa‐human (https://ngdc.cncb.ac.cn/gsa-human), number HRA012013 (CUT&Tag), HRA012014 (ATAC‐Seq), HRA012015 (RNA‐Seq).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 4 November 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 16 authors, 4 keywords, 9 MeSH terms, 4 funders, 114 references.

Cite

This paper

Cheng, K., Wang, Y., Pan, Y., Zhang, W., Yu, D., Zhou, Q., Zhong, Z., Mei, R., Xu, C., Hayierhan, A., Ma, Y., Xu, Y., Xie, Q., Sun, P., Zhou, J., & Zhou, X. (2026). TOP2A Maintains Heterochromatin Stability by Sustaining LMNB1 Expression to Counteract Senescence. Aging cell, 25(11), e70787. https://doi.org/10.1111/acel.70787

BibTeX

@article{cheng2026top2a,
author = {Cheng, Ke and Wang, Yaru and Pan, Yueyuan and Zhang, Wenjun and Yu, Denghong and Zhou, Qi and Zhong, Zhiqian and Mei, Ruyi and Xu, Chaoliang and Hayierhan, Ayidana and Ma, Yumei and Xu, Yien and Xie, Qingdong and Sun, Pingnan and Zhou, Junzhi and Zhou, Xiaoling},
title = {{TOP2A Maintains Heterochromatin Stability by Sustaining LMNB1 Expression to Counteract Senescence}},
journal = {Aging cell},
year = {2026},
month = nov,
volume = {25},
number = {11},
pages = {e70787},
publisher = {Wiley},
issn = {1474-9718},
doi = {10.1111/acel.70787},
url = {https://doi.org/10.1111/acel.70787},
pmid = {42971918},
pmcid = {PMC13727716}
}

RIS

TY - JOUR
AU - Cheng, Ke
AU - Wang, Yaru
AU - Pan, Yueyuan
AU - Zhang, Wenjun
AU - Yu, Denghong
AU - Zhou, Qi
AU - Zhong, Zhiqian
AU - Mei, Ruyi
AU - Xu, Chaoliang
AU - Hayierhan, Ayidana
AU - Ma, Yumei
AU - Xu, Yien
AU - Xie, Qingdong
AU - Sun, Pingnan
AU - Zhou, Junzhi
AU - Zhou, Xiaoling
TI - TOP2A Maintains Heterochromatin Stability by Sustaining LMNB1 Expression to Counteract Senescence
T2 - Aging cell
J2 - Aging Cell
PY - 2026
DA - 2026/11/01
VL - 25
IS - 11
SP - e70787
SN - 1474-9718
PB - Wiley
DO - 10.1111/acel.70787
UR - https://doi.org/10.1111/acel.70787
LA - en
ER -

CSL-JSON

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