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NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice

NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice

Authors :
Jesús Ruiz-Cabello
Ana Victoria Lechuga-Vieco
Bernhard Ryffel
Mario D. Cordero
Antonio J. Pérez-Pulido
Alfonso Varela-López
Fabiola Marín-Aguilar
Beatriz Castejón-Vega
Elísabet Alcocer-Gómez
Alejandro Peralta‐Garcia
Carlos Garrido
Ignacio Flores
José L. Quiles
Javier Lucas
Pedro Bullón
Universidad de Sevilla. Departamento de Estomatología
Universidad de Sevilla. Departamento de Psicología Experimental
Regional Government of Andalusia (España)
Ministerio de Economía y Competitividad (España)
Junta de Andalucía
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Ministerio de Educación, Cultura y Deporte (España)
Comunidad de Madrid
Source :
idUS. Depósito de Investigación de la Universidad de Sevilla, instname, Digibug. Repositorio Institucional de la Universidad de Granada, Repisalud, Instituto de Salud Carlos III (ISCIII), Digital.CSIC. Repositorio Institucional del CSIC, Aging Cell
Publication Year :
2019
Publisher :
John Wiley & Sons Ltd and The Anatomical Society, 2019.

Abstract

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+ 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.<br />This study was supported by a grant from the Andalusian regional government (Grupo de Investigacion Junta de Andalucia CTS113), Consejería de Salud de la Junta de Andalucia: PI‐0036‐2014 and Ministerio de economía y competitividad: SAF2017‐84494‐C2‐1‐R. FMA has the benefit of a FPU Fellowship (FPU 13/03173) from The Ministry of Education, Science and Sport. IF laboratory was funded by grants from Ministerio de Ciencia, Innovación y Universidades (SAF2016‐80406‐R) and Comunidad de Madrid (S2017/BMD‐3875). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV‐2015‐0505)

Details

ISSN :
14749718
Database :
OpenAIRE
Journal :
idUS. Depósito de Investigación de la Universidad de Sevilla, instname, Digibug. Repositorio Institucional de la Universidad de Granada, Repisalud, Instituto de Salud Carlos III (ISCIII), Digital.CSIC. Repositorio Institucional del CSIC, Aging Cell
Accession number :
edsair.doi.dedup.....346d118a900e846bcc002a2f43def481