ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1656442
This article is part of the Research TopicAging Epigenome and LongevityView all 4 articles
Aging-Associated DNA Methylation of LEF1 Modulates Inflammation and Neurodegenerative Pathways
Provisionally accepted
- 1Huashan Hospital, Fudan University, Shanghai, China
- 2Fudan University, Shanghai, China
- 3The First Hospital of Jilin University, Changchun, China
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An increasing number of studies have uncovered genetic pathways and biochemical processes associated with aging. However, identifying reliable biomarkers of aging remains a significant challenge. To investigate molecular alterations during the aging process, we performed comparative analyses of transcriptional profiles of peripheral blood samples from young and elderly human subjects. We found that the expression of LEF1 progressively declined with age. Aging-associated methylation probes were identified in the promoter region of LEF1. Integrative analyses of transcriptomic, chromatin immunoprecipitation sequencing (ChIP-Seq), and other datas revealed that LEF1 is closely linked to immune inflammation and neurodegenerative diseases. These findings were validated through cellular experiments. Knockdown of LEF1 in immune and microglial cell lines led to a marked increase in inflammatory responses, accompanied by elevated levels of reactive oxygen species (ROS). Importantly, in peripheral blood samples from elderly individuals, we confirmed the age-associated downregulation of LEF1 expression along with increased promoter methylation. Supporting this, ChIP-seq and the assay for transposase-accessible chromatin with sequencing (ATACseq) also suggested that epigenetic repression may underlie the age-related silencing of LEF1. Collectively, our findings indicate a critical role for LEF1 in the aging process and suggest that restoring its epigenetic regulation may help reverse aging-associated phenotypes.
Keywords: Aging, DNA Methylation, Inflammation, LEF1, Microglia
Received: 01 Jul 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Chen, Zhou, Gao, Zhong, Chen, Wang, Wang and Xia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rong Xia, Huashan Hospital, Fudan University, Shanghai, China
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