Evidence map›Paper›PMID 40825935›Full record

ArticleCell discovery2025

A phosphorylation switch in the Mediator MED15 controls cellular senescence and cognitive decline.

Haozheng Li, Yuanming Zheng, Chunlei Yuan, Jiayi Wang, Xiaying Zhao, Ming Yang, Defei Xiong, Yenan Yang, Yunpeng Dai, Yiming Gao and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

13 authors.

Haozheng Li *State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
Yuanming Zheng *State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
Chunlei Yuan *State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
Jiayi WangState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
Xiaying ZhaoState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
Ming YangState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
Defei XiongState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
Yenan YangState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
Yunpeng DaiSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Yiming GaoState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
Yuqi WangState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
Lei XueState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
Gang WangState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China. gwang_fd@fudan.edu.cn.ORCID http://orcid.org/0000-0002-4582-501X

Funding

Inner Mongolia Autonomous Region (NMG) 2025KYPT0101Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2022YFA0806200Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2024YFE0215800National Natural Science Foundation of China (National Science Foundation of China) 32030028National Natural Science Foundation of China (National Science Foundation of China) 32170735
6 · The paper itself

Abstract

A hallmark of aging is chronic systemic inflammation, which is exacerbated by the hypersecretory aging phenotype known as the senescence-associated secretory phenotype (SASP). How the SASP is initiated to accelerate tissue inflammation and aging is an outstanding question in aging biology. Here, we showed that phosphorylation of the Mediator subunit MED15 at T603 is able to control the SASP and aging. Transforming growth factor-β selectively induces CDK1-mediated MED15 T603 phosphorylation to control SASP gene expression. The MED15 T603 dephosphorylated mutant (T603A) inhibits the SASP and cell senescence, whereas the T603 phosphorylation-mimicking mutant (T603D) has the opposite effect. Mechanistically, forkhead box protein A1 preferentially binds to unphosphorylated but not phosphorylated MED15 at T603 to suppress SASP gene expression. Notably, aging mice harboring dephosphorylated mutation in this phosphosite exhibit improved learning and memory through the attenuation of the SASP across tissues. Overall, our study indicates that MED15 T603 phosphorylation serves as a control switch for SASP production, which underlies tissue aging and cognitive decline and provides a novel target for age-related pathogenesis.

Identifiers

PMID40825935
PMCPMC12365249

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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.