Aging impairs the neurovascular interface in the heart.
Julian U G WagnerLukas S TomborPedro Felipe MalacarneLisa-Maria KettenhausenJosefine PanthelHaris KujundzicNivethitha ManickamKatja SchmitzMaria CipcaKathrin A StilzAriane FischerMarion Muhly-ReinholzWesley Tyler AbplanalpDavid JohnSarajo K MohantaChristian WeberAndreas J R HabenichtGiulia Karolin BuchmannStephan AngendohrEhsan AminKatharina ScherschelNikolaj KlöckerMalte KelmDominik SchüttlerSebastian ClaussStefan GüntherThomas BoettgerThomas BraunChristian BärMinh-Duc PhamJaya KrishnanSusanne S HilleOliver J MüllerTarik BozogluChristian KupattEleonora NardiniSelma Osmanagic-MyersChristian MeyerAndreas M ZeiherRalf P BrandesGuillermo LuxánStefanie DimmelerPublished in: Science (New York, N.Y.) (2023)
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.
Keyphrases
- heart rate
- cell proliferation
- poor prognosis
- heart failure
- blood pressure
- heart rate variability
- endothelial cells
- left ventricular
- pulmonary hypertension
- long noncoding rna
- peripheral nerve
- induced apoptosis
- dna damage
- machine learning
- atrial fibrillation
- high glucose
- pulmonary artery
- big data
- electronic health record
- stress induced
- artificial intelligence
- coronary artery
- deep learning