Aging impairs the neurovascular interface in the heart
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:381 |
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| Enthalten in: |
Science (New York, N.Y.) - 381(2023), 6660 vom: 25. Aug., Seite 897-906 |
| Sprache: |
Englisch |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 28.08.2023 Date Revised 22.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/science.ade4961 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM361147201 |
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| 100 | 1 | |a Wagner, Julian U G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Aging impairs the neurovascular interface in the heart |
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| 500 | |a Date Revised 22.09.2023 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Tombor, Lukas S |e verfasserin |4 aut | |
| 700 | 1 | |a Malacarne, Pedro Felipe |e verfasserin |4 aut | |
| 700 | 1 | |a Kettenhausen, Lisa-Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Panthel, Josefine |e verfasserin |4 aut | |
| 700 | 1 | |a Kujundzic, Haris |e verfasserin |4 aut | |
| 700 | 1 | |a Manickam, Nivethitha |e verfasserin |4 aut | |
| 700 | 1 | |a Schmitz, Katja |e verfasserin |4 aut | |
| 700 | 1 | |a Cipca, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Stilz, Kathrin A |e verfasserin |4 aut | |
| 700 | 1 | |a Fischer, Ariane |e verfasserin |4 aut | |
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| 700 | 1 | |a Abplanalp, Wesley T |e verfasserin |4 aut | |
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| 700 | 1 | |a Mohanta, Sarajo K |e verfasserin |4 aut | |
| 700 | 1 | |a Weber, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Habenicht, Andreas J R |e verfasserin |4 aut | |
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