衰老是心脏疾病发生的危险因素之一，心肌细胞衰老是心脏功能退行性变化的重要诱因，因此研究心肌细胞衰老的分子机制对预防和治疗衰老性心脏疾病至关重要。本项目以拟采用更接近于人类的非人灵长类动物作为模型，综合运用转录组学、表观遗传组学、蛋白组学等多组学手段，深入解析促进心肌衰老的关键因子和通路。我们的前期研究基础通过整合多组学数据，已经发现SIRT2表达下调是年老猴心脏组织重要的分子生物学特征。SIRT2家族属III类组蛋白脱乙酰化酶，是连接表观遗传调控和寿命的重要分子节点。以此为关键切入点，我们将结合CRISPR/Cas9基因组靶向修饰技术和多能干细胞向心肌定向分化技术，深入研究SIRT2调控灵长类心肌细胞衰老的分子机制。

Aging is one of the risk factors for heart disease. Cardiomyocyte aging is an important cause of degenerative changes in cardiac function. Therefore, studying the molecular mechanism of cardiomyocyte aging is essential for the prevention and treatment of aging heart disease. This project uses non-human primates that are closer to humans as a model, comprehensively applies transcriptomics, epigenetics, proteomics, and other omics to deeply analyze the key factors and pathways that promote myocardial aging. Our previous research foundation has found that down-regulation of SIRT2 expression is an important molecular biological feature of aged monkey heart tissue by integrating multi-omics data. The SIRT2 family belongs to class III histone deacetylases and is an important molecular node connecting epigenetic regulation and longevity. With this as a key entry point, we will combine the technologies of CRISPR/Cas9 based gene targeting and differentiation from pluripotent stem cells into cardiomyocytes to deeply study the molecular mechanism of SIRT2 in regulating primate cardiomyocyte senescence.