Evidence map›Paper›PMID 40918098›Full record

ArticleFrontiers in immunology2025

Aging-associated DNA methylation of LEF1 modulates inflammation and neurodegenerative pathways.

Mengke Chen, Lujie Zhou, Yidan Gao, Yao Zhong, Cheng Chen, Zhicheng Wang, Xiaoning Wang, Rong Xia

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

8 authors.

Mengke Chen *Department of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, China.
Lujie Zhou *Department of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, China.
Yidan GaoShanghai Institute of Infectious Disease and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, China.
Yao ZhongDepartment of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, China.
Cheng ChenDepartment of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, China.
Zhicheng WangDepartment of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, China.
Xiaoning WangDepartment of Blood Transfusion, The First Hospital of Jilin University, Changchun, China.
Rong XiaDepartment of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Aging is accompanied by profound changes in immune regulation and epigenetic landscapes, yet the molecular drivers underlying these alterations are not fully understood. Methods: Transcriptional profiles of peripheral blood samples from young and elderly individuals, together with aging-associated methylation probe data, were used to identify aging biomarkers. Transcriptomics and chromatin immunoprecipitation sequencing (ChIP-Seq) were conducted to explore potential regulatory mechanisms. Functional validation was performed via knockdown in immune and microglial cell lines, assessing inflammatory responses and reactive oxygen species (ROS) levels. Finally, an independent cohort was recruited to validate expression and promoter methylation, with ChIP-seq and the assay for transposase-accessible chromatin with sequencing (ATAC-seq) analyses supporting epigenetic repression as the underlying mechanism. Results: LEF1 expression was significantly downregulated in elderly individuals, accompanied by increased promoter methylation, indicating age-related epigenetic repression. Integrated multi-omics analysis linked LEF1 to immune inflammation and neurodegenerative pathways. LEF1 knockdown enhanced inflammatory responses and ROS production in vitro. ChIP-seq and ATAC-seq data supported epigenetic repression as a mechanism for age-related LEF1 silencing. Conclusions: Age-related epigenetic repression of LEF1 contributes to immune-inflammatory activation and may underlie neurodegenerative processes.

Indexed as

AgingDNA MethylationInflammationLymphoid Enhancer-Binding Factor 1Neurodegenerative DiseasesAdultAgedAged, 80 and overEpigenesis, GeneticFemaleHumansMaleMiddle AgedPromoter Regions, GeneticReactive Oxygen SpeciesYoung AdultLEF1 protein, humanLymphoid Enhancer-Binding Factor 1Reactive Oxygen SpeciesagingDNA methylationinflammationLEF1microglia

Identifiers

PMID40918098
PMCPMC12408614

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.