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损伤的反应至关重要。这样的研究有望识别细胞和分子的变化，并有助于开发新的治疗策略，以改善组织重塑和愈合。在这项提案中，我们着手提供衰老对巨噬细胞的表型和功能的影响的更深入的理解，巨噬细胞是高度丰富的，有助于组织稳态和对损伤的先天免疫反应。我们推测巨噬细胞程序的年龄依赖性变化导致对急性和慢性心肌损伤的炎症和愈合反应的改变。我们将在心脏损伤的老龄小鼠中进行深度免疫表型分析。我们将集中在两个重要的实体心脏损伤，我们将模型在各种巨噬细胞报告小鼠：心肌梗死和心力衰竭。我们将比较来自小鼠实验的结果与已发表的数据（Human Heart Atlas），以及心肌病患者队列的组织标本，以验证我们的发现，并为我们的转化研究提供进一步的临床背景。 鉴定衰老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，这对于不断增长的老年人口至关重要。

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.