Targeting KAT8 Alleviates Vascular Senescence by Modulating the INHBA/TGF-β Pathway.

Zhongxiao Lin, Jianyu Xiong, Fuyuan Zhang, Hao Zhang, Menglin Zhu, Caiyu Li, Rong Fu, Zhongyi Zhang, Qinwen Hu, Jie Liang, Bohan Fu, Chiyuan Ma, Kehan Jin, Liuyi Lu, Junmeng Zheng, Brian Tomlinson, Xi-Yong Yu, Yi Zhun Zhu

Laboratory for the Drug Discovery from Natural Resources and School of Pharmacy, Macau University of Science and Technology, Macau, China; Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA Key Laboratory, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, PR China.Laboratory for the Drug Discovery from Natural Resources and School of Pharmacy, Macau University of Science and Technology, Macau, China; Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA Key Laboratory, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, PR China. · pubmed

Paper

Abstract

Vascular senescence is a fundamental driver of age-related cardiovascular diseases, yet the epigenetic mechanisms controlling this process remain poorly understood. This study investigated the role and underlying mechanisms of lysine acetyltransferase 8 (KAT8), a key histone acetyltransferase, in maintaining endothelial cell homeostasis and preventing vascular senescence. We found that KAT8 expression is consistently downregulated in human aged vessels, senescent rats and mice, and in cellular models of aging. Using CRISPR/Cas9-based loss-of-function and gain-of-function approaches in endothelial cells, C57BL/6J mice, and ApoE

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Research summary

Targeting KAT8 can alleviate vascular senescence by modulating the INHBA/TGF-β pathway. This paper addresses the epigenetic mechanisms of vascular senescence, which is a fundamental aspect of aging and age-related diseases, making it relevant to longevity research.

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