Immune responses following myocardial infarction in aged mice

Aging is a major risk factor for cardiovascular diseases and is often accompanied by systemic alterations of the immune system, such as the accumulation of terminally differentiated T cells, clonal hematopoiesis of intermediate potential, and dysregulated production of pro-inflammatory cytokines. However, how the aging immune system impacts post-myocardial infarction (MI) repair remains poorly understood. In the present study, we compared the post-MI inflammatory responses in 2- and 18-month-old C57BL/6 J mice of both sexes and monitored the distribution of interferon-gamma (IFN-γ) producing cells in these conditions using Ifng -YFP reporter mice. Our results show a conserved IFN-γ production signature both in mice and humans during physiological aging. In mice, the aging myocardium exhibited increased pro-inflammatory gene expression signature with increased recruitment of IFN-γ-expressing T cells following MI. Moreover, while this age-related inflammation had little impact in the acute post-MI responses, a persistent IFN-γ-production signature observed in elderly mice was associated with an aggravation of chronic adverse cardiac remodeling. Taken together, our results indicate that age-related smoldering inflammation may fuel the long-term progression of ischemic heart failure.