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Cited by 220Inflammasome and immune disordersGenetics, Aging, and Longevity in Model OrganismsCardiac Fibrosis and Remodeling

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

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Marín‐Aguilar, Fabiola, Lechuga‐Vieco, Ana V., Alcocer‐Gómez, Elísabet, Castejón‐Vega, Beatriz, Lucas, Javier, Garrido, Carlos, Peralta‐Garcia, Alejandro, Pérez‐Pulido, Antonio J. +7 more·2020·Aging Cell
DOI 10.1111/acel.13050PMC PMC6974709
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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.

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Authors
Marín‐Aguilar, F., Lechuga‐Vieco, A. V., Alcocer‐Gómez, E., Castejón‐Vega, B., Lucas, J., Garrido, C., Peralta‐Garcia, A., Pérez‐Pulido, A. J., Varela‐López, A., Quiles, J. L., Ryffel, B., Flores, I., Bullón, P., Ruiz‐Cabello, J., & Cordero, M. D.
Affiliations
  • Universidad de Sevilla (ES)
  • Spanish National Centre for Cardiovascular Research (ES)
  • Consejo Superior de Investigaciones Científicas (ES)
  • Universidad de Granada (ES)
  • Université d'Orléans (FR)
  • CIBER de Enfermedades Respiratorias (CIBERES) Madrid Spain
Corresponding author
Cordero, Mario D.
ORCID
Venue
Aging Cell
Publisher
Wiley
Published
2019-10-18
Volume
19
Issue
1
Pages
e13050-e13050
ISSN
  • 1474-9718 (ISSN-L)
  • 1474-9726
DOI
10.1111/acel.13050
PMC
PMC6974709
OpenAlex
W2981170486
Cited by
220
References
46
Citations by year
2026: 33 · 2025: 40 · 2024: 39 · 2023: 29 · 2022: 25 · 2021: 31 · 2020: 23
FWCI
6.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Aging Cell (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • Institutional Repository of the University of Granada (University of Granada) (submittedVersion, cc-by)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
  • idUS (Universidad de Sevilla) (submittedVersion, public-domain)
  • Deposito de Investigacion Universidad de Sevilla (University of Seville) (submittedVersion, cc-by-nc-nd)
Funders
  • Andalusian regional government
  • Consejería de Salud de la Junta de Andalucia (PI-0036-2014)
  • Ministerio de economía y competitividad (SAF2017-84494-C2-1-R)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
NLRP3 inflammasome, cardiac aging, longevity, atrial fibrillation, insulin resistance, autophagy, PI3K/AKT/mTOR pathway, telomere shortening, insulin-like growth factor I, leptin/adiponectin ratio, visfatin, SIRT1, NAD+, cardiac function, lifespan extension
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Cardiovascular System, Longevity, Male, Signal Transduction, Mice, Inflammasomes

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