DataVXAdvanced SciencePaper
journal article·2026-01Open access

Targeting Endothelial KDM5A to Attenuate Aging and Ameliorate Age‐Associated Metabolic Abnormalities

Rifeng Gao, Lifeng Liang, Ling Yang, Chunyu Lyu, Yang Lyu, Weijun Yang, Jiaran Shi, Wei Wei, Jiahui Cheng, Xiaolei Sun, Xian Zhu, Chao Chen, Xiaoting Xu, Jianchuang Qi, Wenli Li, Yizhe Zhang, Xiao Zhang, Yan Zhou, Aiqiang Dong, Juntao Chen, Bo Li, Kun Yang

Advanced Science· Volume 13· Issue 6
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Source abstract

Abstract

Abstract Vascular aging accelerates the gradual deterioration of systemic organ function, yet its key driving factors are still largely unexplored. Here, it is demonstrated that lysine‐specific demethylase 5A (KDM5A) decreases and histone H3 lysine 4 (H3K4me3) increases in vascular endothelial cells (VECs) isolated from ageing mice and VEC senescence models. KDM5A deficiency exacerbated endothelial cell aging in vitro. Endothelial‐specific KDM5A‐deficient mice exhibit shortened lifespan and multiple senescent phenotypes, including fat accumulation, reduced thermogenic capacity, skeletal kyphosis, and age‐related liver lesions, while maintaining VECs‐specific KDM5A levels attenuates these adverse metabolic abnormalities and prolongs lifespan. Mechanistically, endothelial KDM5A deficiency aggravates aging‐associated fatty acid (FA) metabolism disorders by enhancing H3K4me3 enrichment at the promoter region of FA‐binding protein 4 ( FABP4 ), which leads to active FABP4 transcription. Together, the study reveals the regulatory mechanisms of KDM5A in age‐dependent metabolic disorders and identifies KDM5A/FABP4 axis as a potential therapeutic target for vascular aging and related organ dysfunction.
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Research context

OpenAlex topics: Epigenetics and DNA Methylation · Peroxisome Proliferator-Activated Receptors · Kruppel-like factors research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Cardiac Surgery, The Second Affiliated Hospital Zhejiang University Hangzhou 310009 China

Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital Capital Medical University Beijing 100029 China

Department of Ultasonography, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200127 China

School of Nursing Zhejiang Chinese Medical University Hangzhou 310053 China

Department of Cardiology, Shanghai Fifth People's Hospital Fudan University Shanghai 200240 China

Department of Cardiology Lihuili Hospital Facilitated to Ningbo University Ningbo 315048 China

Department of Radiology Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200127 China

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University Shanghai 200232 China

Department of Anesthesiology Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200127 China

Key Laboratory of Anesthesiology (Shanghai Jiao Tong University) Ministry of Education Shanghai 200127 China

Department of Urology, The Second Affiliated Hospital Zhejiang University Hangzhou 310009 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Shanghai Municipality

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