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Aging impairs the neurovascular interface in the heart
Ist Teil von
Science (American Association for the Advancement of Science), 2023-08, Vol.381 (6660), p.897-906
Ort / Verlag
United States: The American Association for the Advancement of Science
Erscheinungsjahr
2023
Quelle
Science Online_科学在线
Beschreibungen/Notizen
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
expression or endothelial
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
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.