Urolithin A Provides Cardioprotection and Mitochondrial Quality Enhancement Preclinically and Improves Cardiovascular Health Biomarkers in Humans

Cardiovascular diseases (CVDs) remain the primary cause of global mortality. Nutritional interventions hold promise to reduce CVD risks in an increasingly aging population. However, few nutritional interventions are proven to support heart health and act mostly on blood lipid homeostasis rather than at cardiac cell level. Here, we show that mitochondrial quality and dysfunction are a common hallmark in human cardiomyocytes upon heart aging and in chronic conditions. Preclinically, the post-biotic and mitophagy activator, Urolithin A (UA), reduced both systolic and diastolic cardiac dysfunction in models of natural aging and heart failure. At a cellular level, this was associated with a recovery of mitochondrial ultrastructural defects and mitophagy. In humans, UA supplementation for 4 months in healthy older adults significantly reduced plasma ceramides clinically validated to predict CVD risks. These findings extend and translate UA’s benefits to heart health, making UA a promising nutritional intervention to support cardiovascular function as we age.心血管疾病（CVDs）仍是全球范围内致死的首要病因。在人口老龄化程度持续加深的当下，营养干预手段有望降低心血管疾病的发病风险。然而，经临床证实可维护心脏健康的营养干预手段寥寥无几，且现有干预大多仅作用于血脂稳态层面，而非靶向心肌细胞。本研究证实，线粒体质量异常与功能失调是人类心肌细胞（cardiomyocytes）在心脏衰老及慢性病变状态下的共同标志性特征。临床前研究表明，后生元类线粒体自噬（mitophagy）激活剂尿石素A（UA）可在自然衰老与心力衰竭动物模型中，同时改善心脏收缩与舒张功能障碍。在细胞层面，该改善效应与线粒体超微结构缺陷的修复及线粒体自噬功能的恢复密切相关。人体临床试验结果显示，健康老年人群连续4个月补充UA，可显著降低血浆神经酰胺水平——该指标已通过临床验证，可用于预测心血管疾病发病风险。本研究的发现将UA的获益范畴拓展至心脏健康领域，使其有望成为助力衰老人群维持心血管功能的新型营养干预手段。