NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice
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- Fabiola Marín‐Aguilar
- Research Laboratory Oral Medicine Department University of Sevilla Sevilla Spain
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- Ana V. Lechuga‐Vieco
- Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) Madrid Spain
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- Elísabet Alcocer‐Gómez
- Departamento de Psicología Experimental Facultad de Psicología Universidad de Sevilla Seville Spain
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- Beatriz Castejón‐Vega
- Research Laboratory Oral Medicine Department University of Sevilla Sevilla Spain
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- Javier Lucas
- Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) Madrid Spain
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- Carlos Garrido
- Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) Madrid Spain
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- Alejandro Peralta‐Garcia
- Centro Andaluz de Biología del Desarrollo (CABD) Universidad Pablo de Olavide‐CSIC‐Junta de Andalucía Sevilla Spain
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- Antonio J. Pérez‐Pulido
- Centro Andaluz de Biología del Desarrollo (CABD) Universidad Pablo de Olavide‐CSIC‐Junta de Andalucía Sevilla Spain
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- Alfonso Varela‐López
- Institute of Nutrition and Food Technology "José Mataix Verdú" Department of Physiology Biomedical Research Center University of Granada Granada Spain
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- José L. Quiles
- Institute of Nutrition and Food Technology "José Mataix Verdú" Department of Physiology Biomedical Research Center University of Granada Granada Spain
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- Bernhard Ryffel
- Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM) UMR 7355 CNRS‐University of Orleans Orléans France
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- Ignacio Flores
- Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) Madrid Spain
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- Pedro Bullón
- Research Laboratory Oral Medicine Department University of Sevilla Sevilla Spain
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- Jesús Ruiz‐Cabello
- CIBER de Enfermedades Respiratorias (CIBERES) Madrid Spain
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- Mario D. Cordero
- Institute of Nutrition and Food Technology "José Mataix Verdú" Department of Physiology Biomedical Research Center University of Granada Granada Spain
説明
<jats:title>Abstract</jats:title><jats:p>While NLRP3‐inflammasome has been implicated in cardiovascular diseases, its role in physiological cardiac aging is largely unknown. During aging, many alterations occur in the organism, which are associated with progressive impairment of metabolic pathways related to insulin resistance, autophagy dysfunction, and inflammation. Here, we investigated the molecular mechanisms through which NLRP3 inhibition may attenuate cardiac aging. Ablation of NLRP3‐inflammasome protected mice from age‐related increased insulin sensitivity, reduced IGF‐1 and leptin/adiponectin ratio levels, and reduced cardiac damage with protection of the prolongation of the age‐dependent PR interval, which is associated with atrial fibrillation by cardiovascular aging and reduced telomere shortening. Furthermore, old NLRP3 KO mice showed an inhibition of the PI3K/AKT/mTOR pathway and autophagy improvement, compared with old wild mice and preserved Nampt‐mediated NAD<jats:sup>+</jats:sup> levels with increased SIRT1 protein expression. These findings suggest that suppression of NLRP3 prevented many age‐associated changes in the heart, preserved cardiac function of aged mice and increased lifespan.</jats:p>
収録刊行物
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- Aging Cell
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Aging Cell 19 (1), e13050-, 2019-10-18
Wiley