Age-Induced Accumulation of Succinate Promotes Cardiac Fibrogenesis.
Ziwen WangShu YangZheng PingYaqi LiTing JiangXin ZhengZiyuan ZhangGuan WangZhaochuan LiuHaimei SunQi ZhangHeyang ZhangYang GaoYouxin FengXixi LiuLizhuang HanShiqi LinXiaowei ZhangMeng-Meng SongTong LiuMeng TangChenan LiuHailun XieGuotian RuanMing YangYue ChenXiaohan YuanDongying WangXiaoli ZhangChenyang WangZhongyong JiangYing XuLong ChenLi DengBo WuDeshan ZhouXuebin CaoHan Ping ShiTing-Yi SunPublished in: Circulation research (2023)
Our findings indicate that targeting metabolic dysregulation has significant implications for the treatment of age-related cardiac fibrosis and diastolic dysfunction. We further demonstrate a novel mechanism by which succinate induces fibroblast activation and apoptosis resistance by promoting PKM2 dimerization. Hence, inhibiting succinate generation or blocking its downstream effects is potentially a promising new strategy for slowing the heart aging.