Impact of aging on macrophage immune responses in myocardial injury

衰老对免疫系统的影响及其对组织损伤和炎症的后果在很大程度上是未知的。然而，在老龄化的人口中，了解年轻人和成年人之间的免疫功能和对伤害的反应是至关重要的。这类研究有望确定细胞和分子的变化，并有助于开发新的治疗策略，以改善组织重塑和愈合。在这项建议中，我们试图更深入地了解衰老对巨噬细胞表型和功能的影响，巨噬细胞高度丰富，对组织动态平衡和对损伤的先天免疫反应都有贡献。我们假设，巨噬细胞程序中年龄相关的变化会导致对急性和慢性心肌损伤的炎症和愈合反应的改变。我们将对心脏损伤的老龄小鼠进行深度免疫表型鉴定。我们将关注心脏损伤的两个重要实体，我们将在不同的巨噬细胞报告小鼠中建立这种损伤的模型：心肌梗死和心力衰竭。我们将把我们的小鼠实验结果与已发表的数据(人类心脏图谱)以及一名心肌病患者的组织样本进行比较，以验证我们的发现，并为我们的翻译研究提供进一步的临床背景。识别老化心脏中的巨噬细胞免疫可能有助于开发治疗心脏疾病的新策略，鉴于日益增长的老年人口，这是至关重要的。

The impact of aging on the immune system and its consequences for tissue injury and inflammation is largely unknown. However, in an ageing population it is of pivotal importance to understand immune functions and response to injury between young and adult. Such research can be expected to identify cellular and molecular changes and contribute to the development of novel therapeutic strategies to improve tissue remodelling and healing. In this proposal we set out to provide a deeper understanding of the impact of aging on the phenotype and function of macrophages, which are highly abundant and contribute both to tissue homeostasis and innate immune responses to injury. We hypothesize that age-dependent changes in macrophage programs lead to altered inflammatory and healing responses to acute and chronic myocardial injury. We will carry out deep immune phenotyping in aging mice subjected to cardiac injury. We will focus on two important entities of cardiac injury, which we will model in various macrophage reporter mice: myocardial infarction and heart failure. We will compare our results derived from mouse experiments with published data (Human Heart Atlas), as well as tissue specimen of a patient cohort with cardiomyopathy, to validate our findings and provide further clinical context of our translational research. Identification of macrophage immunity in the aging heart may help to develop novel strategies for the treatment of cardiac diseases, which is of pivotal importance in the light of a growing elderly population.