As modern life conditions and medical care have remarkably improved, the current society increasingly age. However, while a prolonged life-span is an undoubtable triumph, age-associated pathologies such as cardiovascular diseases increase. Hence understanding cardiovascular ageing is one key to improve not only the life- but also the health-span.
In this regard, the endothelium has gained special attention. It was shown in the bone-marrow, the liver and the lungs, that endothelial cells maintain tissue homeostasis and may exert reparative functions in a paracrine manner. However, the role of endothelial cells in cardiac aging remains less clear.
In our current study, we have discovered a significant upregulation in the expression and release of the axon-repelling factor Semaphorin-3A by endothelial cells, resulting in the regression of nervous fibers in the aging left ventricle of the heart. Remarkably, this upregulation of Semaphorin-3A was found to be triggered by the downregulation of miR-145, a microRNA that diminishes in the aged heart. Intriguingly, this process appears to be closely tied to cellular senescence.
Through a comprehensive examination of mice throughout their adult lifespan, we observed a sudden decline in cardiac innervation occurring at 16 months of age, concurrent with the development of cellular senescence within the heart tissue. Moreover, the expression levels of miR-145 and Semaphorin-3A were closely associated with the senescence process. The regression of nervous fibers had a direct impact on heart rate variability in aged mice, a phenomenon that was successfully reversed by administering two senolytic drugs, dasatinib and quercetin, to eliminate cellular senescence. Additionally, also the nervous regression and Semaphorin-3A expression were reversed in these hearts.
In summary, our findings shed light on the relationship between endothelial senescence and the neuro-vascular interface during cardiac aging. Understanding and targeting these mechanisms hold promise for novel therapeutic approaches to tackle cardiovascular diseases.
Find the full article here:
Aging impairs the neurovascular interface in the heart | Science
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