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

Marín‐Aguilar, F. et al. (2020) NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice. Aging Cell, 19(1), e13050. (doi: 10.1111/acel.13050) (PMID:31625260) (PMCID:PMC6974709)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Castejon Vega, Dr Beatriz
• 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., and Cordero, M. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Aging Cell
• Publisher: Wiley
• ISSN: 1474-9718
• ISSN (Online): 1474-9726
• Published Online: 18 October 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Aging Cell 19(1): e13050
• Publisher Policy: Reproduced under a Creative Commons License