ARID5A orchestrates cardiac aging and inflammation through MAVS mRNA stabilization.

Yanling Fan, Yandong Zheng, Yiyuan Zhang, Gang Xu, Chun Liu, Jianli Hu, Qianzhao Ji, Shuo Zhang, Shuaiqi Fang, Jinghui Lei, Lan-Zhu Li, Xing Wang, Xi Xu, Cui Wang, Si Wang, Shuai Ma, Moshi Song, Wenjian Jiang, Junming Zhu, Yijia Feng, Jiangang Wang, Ying Yang, Guodong Zhu, Xiao-Li Tian, Hongjia Zhang, Weihong Song, Jiayin Yang, Yan Yao, Guang-Hui Liu, Jing Qu, Weiqi Zhang

China National Center for Bioinformation, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.China National Center for Bioinformation, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. · pubmed

Paper

Abstract

Elucidating the regulatory mechanisms of human cardiac aging remains a great challenge. Here, using human heart tissues from 74 individuals ranging from young (≤35 years) to old (≥65 years), we provide an overview of the histological, cellular and molecular alterations underpinning the aging of human hearts. We decoded aging-related gene expression changes at single-cell resolution and identified increased inflammation as the key event, driven by upregulation of ARID5A, an RNA-binding protein. ARID5A epi-transcriptionally regulated Mitochondrial Antiviral Signaling Protein (MAVS) mRNA stability, leading to NF-κB and TBK1 activation, amplifying aging and inflammation phenotypes. The application of gene therapy using lentiviral vectors encoding shRNA targeting ARID5A into the myocardium not only mitigated the inflammatory and aging phenotypes but also bolstered cardiac function in aged mice. Altogether, our study provides a valuable resource and advances our understanding of cardiac aging mechanisms by deciphering the ARID5A-MAVS axis in post-transcriptional regulation.

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Research summary

The paper claims that ARID5A regulates MAVS mRNA stability, influencing cardiac aging and inflammation. This research is relevant as it addresses the underlying mechanisms of cardiac aging, potentially contributing to our understanding of aging processes and interventions that could mitigate age-related decline in cardiac function.

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