Evidence map›Paper›PMID 40849896›Full record

ArticleAging cell2025

KDM4 Orchestrates Epigenomic Remodeling of Senescent Cells and Potentiates the Senescence-Associated Secretory Phenotype.

Boyi Zhang, Qilai Long, Shanshan Wu, Qixia Xu, Shuling Song, Liu Han, Min Qian, Xiaohui Ren, Hanxin Liu, Jing Jiang and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Stem Cells in Aging and Anti-Aging.Stem cell reviews and reports · 2026
    Review
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Boyi ZhangShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Qilai LongDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Shanshan WuShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Qixia XuInstitute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Shuling SongShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Liu HanShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Min QianShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Xiaohui RenShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Hanxin LiuDepartment of Pharmacology, Binzhou Medical University, Yantai, Shandong, China.
Jing JiangDepartment of Pharmacology, Binzhou Medical University, Yantai, Shandong, China.
Jianming GuoDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Xiaoling ZhangDepartment of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0002-0134-1347
Xing ChangKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Qiang FuDepartment of Pharmacology, Binzhou Medical University, Yantai, Shandong, China.ORCID 0000-0002-6932-7103
Eric W-F LamDepartment of Surgery and Cancer, Imperial College London, London, UK.
Judith CampisiBuck Institute for Research on Aging, Novato, California, USA.
James L KirklandCenter for Advanced Gerotherapeutics, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Yu SunShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Funding

Targeting Cellular Senescence to Extend HealthspanP01AG062413 · NIA · MAYO CLINIC ROCHESTER · PI Sundeep Khosla, Nathan K LeBrasseur · 2019 to 2026
$28.7M
Effect of Aging on Preadipocyte DifferentiationR37AG013925 · NIA · MAYO CLINIC ROCHESTER · PI KIRKLAND, JAMES L. · 2016 to 2025
$6.6M
Effect of Aging on Preadipocyte DifferentiationR01AG013925 · NIA · MAYO CLINIC ROCHESTER · PI KIRKLAND, JAMES L. · 1997 to 2012
$3.7M
NIA NIH HHS P01 AG062413NIA NIH HHS R01 AG013925NIA NIH HHS R37 AG013925Strategic Priority Research Program of Chinese Academy of Sciences XDB39010500
6 · The paper itself

Abstract

Cellular senescence restrains the expansion of neoplastic cells through several layers of regulation. We report that the histone H3-specific demethylase KDM4 is expressed as human stromal cells undergo senescence. In clinical oncology, upregulated KDM4 and diminished H3K9/H3K36 methylation correlate with poorer survival of patients with prostate cancer after chemotherapy. Global chromatin accessibility mapping via assay for transposase-accessible chromatin with high-throughput sequencing, and expression profiling through RNA sequencing, reveals global changes of chromatin openness and spatiotemporal reprogramming of the transcriptomic landscape, which underlie the senescence-associated secretory phenotype (SASP). Selective targeting of KDM4 dampens the SASP of senescent stromal cells, promotes cancer cell apoptosis in the treatment-damaged tumor microenvironment, and prolongs survival of experimental animals. Our study supports dynamic changes of H3K9/H3K36 methylation during senescence, identifies an unusually permissive chromatin state, and unmasks KDM4 as a key SASP modulator. KDM4 targeting presents a new therapeutic avenue to manipulate cellular senescence and limit its contribution to age-related pathologies, including cancer.

Indexed as

Cellular SenescenceEpigenesis, GeneticEpigenomicsJumonji Domain-Containing Histone DemethylasesSenescence-Associated Secretory PhenotypeAnimalsCell Line, TumorHistonesHumansMaleMiceProstatic NeoplasmsHistonesJumonji Domain-Containing Histone DemethylasesKDM4A protein, humanage‐related pathologyagingcellular senescenceepigenetic modificationH3K9/H3K36 demethylationKDM4

Identifiers

PMID40849896
PMCPMC12507408

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.