Scholarlink

<p>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 (<i>MAVS</i>) 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 <i>ARID5A</i> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

ARID5A orchestrates cardiac aging and inflammation through MAVS mRNA stabilization

  • 期刊论文

  • 发表日期：

    2025年4月29日

查看全文
  • 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

摘要

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.