Impact of aging on macrophage immune responses in myocardial injury

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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.