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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
- 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)
- Subjects :
- 0301 basic medicine
Cardiac function curve
Male
Aging
medicine.medical_specialty
autophagy
Inflammasomes
Longevity
Inflammation
morbidity
Biology
Cardiovascular System
03 medical and health sciences
Mice
0302 clinical medicine
Insulin resistance
Internal medicine
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Autophagy
Animals
Mortality
Protein kinase B
PI3K/AKT/mTOR pathway
NLRP3‐inflammasome
Cardiac aging
Adiponectin
integumentary system
Leptin
Cell Biology
Original Articles
medicine.disease
mortality
030104 developmental biology
Endocrinology
Original Article
NLRP3-inflammasome
medicine.symptom
Morbidity
030217 neurology & neurosurgery
cardiac aging
Signal Transduction
Subjects
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