Thursday, August 31, 2023

Aging impairs the neurovascular interface in the heart

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"... In a new Science study, researchers demonstrate that aging or “senescent” blood vessels release a protein called semaphorin-3A, which inhibits the growth of nerve cells in cardiac muscle tissue.

The release of semaphorin-3A is “nerve-wracking” for the aging heart ... A healthy heart can independently control its own rhythm, but reduced nerve density causes it to beat irregularly. The lack of nerves also impairs the heart’s ability to function effectively under stress, since it can no longer respond as well to signals from the brain telling it to pump faster and supply more oxygen. ..." (Source)

From the editor's summary and abstract:
"Editor’s summary
Changes in innervation of the heart can contribute to arrhythmias, and the risk of arrhythmias greatly increases with age. Wagner et al. uncovered a mechanism connecting these two phenomena. The authors studied young and aging mice and demonstrated that innervation of the heart decreases with age. Age-related accumulation of senescent cells promotes the release of semaphorin-3A, which reduces the density of neuronal axons in the heart. At the same time, aging is associated with a decrease in a microRNA that counteracts the effects of semaphorin-3A, further tipping the balance toward decreased innervation. These age-related losses in innervation could be reversed by treating the mice with senolytic drugs, suggesting a potential therapeutic approach. ...
Abstract
Aging is a major risk factor for impaired cardiovascular health. Because the aging myocardium is characterized by microcirculatory dysfunction, and because nerves align with vessels, we assessed the impact of aging on the cardiac neurovascular interface. We report that aging reduces nerve density in the ventricle and dysregulates vascular-derived neuroregulatory genes. Aging down-regulates microRNA 145 (miR-145) and derepresses the neurorepulsive factor semaphorin-3A. miR-145 deletion, which increased Sema3a expression or endothelial Sema3a overexpression, reduced axon density, mimicking the aged-heart phenotype. Removal of senescent cells, which accumulated with chronological age in parallel to the decline in nerve density, rescued age-induced denervation, reversed Sema3a expression, preserved heart rate patterns, and reduced electrical instability. These data suggest that senescence-mediated regulation of nerve density contributes to age-associated cardiac dysfunction."

Aging impairs the neurovascular interface in the heart | Science

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