Maps of inflammaging reveal the heart does not age evenly
Scientists have long known that aging drives inflammation in the heart, but exactly how those changes are distributed throughout the organ has remained unclear. Now, a team from The Jackson Laboratory (JAX) has pinpointed hotspots where these "inflammaging" signals concentrate, providing a new map of cardiac aging and a foundation for future studies of cardiovascular health and decline.
Scientists have long understood that aging leads to inflammation in the heart, but the distribution of these age-related changes within the organ has been uncertain. A team from The Jackson Laboratory (JAX) has now identified specific hotspots where inflammation and scarring signals concentrate in the heart, providing a detailed map of cardiac aging.
In a study published in Aging Cell, researchers found that cellular markers associated with age-related inflammation and scarring were concentrated in the aortic valves and aortic root, which are critical areas where immune and connective tissue cells interact differently as the heart ages. Study leader Nadia Rosenthal noted that aging should be viewed as a non-linear process, as organs and tissues do not age at the same rate, even within an individual.
Previous research primarily focused on heart muscle cells, particularly the left ventricle, but this study examined the entire heart, revealing that valves and major blood vessels, often considered part of the heart's "plumbing," contain many of the cells of interest. This discovery challenges the conventional view that heart muscle cells are the primary targets of aging.
The researchers used single-cell and spatial genomics technologies to analyze thousands of cells from young and aged mouse hearts, revealing that macrophages showed increased activity in genes linked to inflammation and tissue remodeling, while fibroblasts became more prone to fibrosis. Interestingly, some age-related markers were present in young hearts, suggesting that these markers do not necessarily indicate senescence.
The study also identified two key genes, Ccl8 and Cdkn1a, whose expression increased with age in specific regions of the heart, indicating localized hubs of cardiac aging. These findings highlight the importance of considering the heart as a complex system where different cell types communicate and contribute to aging-related changes, with potential implications for understanding sex-based differences in cardiovascular disease progression.
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