@misc{10481/75989,
year = {2022},
month = {6},
url = {http://hdl.handle.net/10481/75989},
abstract = {Age and age-dependent inflammation are two main risk factors for cardiovascular diseases.
Aging can also affect clock gene-related impairments such as chronodisruption and has been linked
to a decline in melatonin synthesis and aggravation of the NF- B/NLRP3 innate immune response
known as inflammaging. The molecular drivers of these mechanisms remain unknown. This study
investigated the impact of aging and NLRP3 expression on the cardiac circadian system, and the
actions of melatonin as a potential therapy to restore daily rhythms by mitigating inflammaging. We
analyzed the circadian expression and rhythmicity of clock genes in heart tissue of wild-type and
NLRP3-knockout mice at 3, 12, and 24 months of age, with and without melatonin treatment. Our
results support that aging, NLRP3 inflammasome, and melatonin affected the cardiac clock genes
expression, except for Rev-erba, which was not influenced by genotype. Aging caused small phase
changes in Clock, loss of rhythmicity in Per2 and Rora, and mesor dampening of Clock, Bmal1, and
Per2. NLRP3 inflammasome influenced the acrophase of Clock, Per2, and Rora. Melatonin restored the
acrophase and the rhythm of clock genes affected by age or NLRP3 activation. The administration of
melatonin re-established murine cardiac homeostasis by reversing age-associated chronodisruption.
Altogether, these results highlight new findings about the effects aging and NLRP3 inflammasome
have on clock genes in cardiac tissue, pointing to continuous melatonin as a promising therapy to
placate inflammaging and restore circadian rhythm in heart muscle. Additionally, light microscopy
analysis showed age-related morphological impairments in cardiomyocytes, which were less severe
in mice lacking NLRP3. Melatonin supplementation preserved the structure of cardiac muscle fibers
in all experimental groups.},
organization = {Instituto de Salud Carlos III (Ministerio de Economia y Competitividad, Spain) (European Regional Development Fund/European Social Fund "Investing in your future")	PI13-981	
PI16-00519	
PI19-01372	
CB16-10-00238	
CB16/10/00239},
organization = {Junta de Andalucia	CTS-101},
organization = {Spanish Government},
publisher = {MDPI},
keywords = {Melatonin},
keywords = {Clock genes},
keywords = {Chronodisruption},
keywords = {Rhythm},
keywords = {Aging},
keywords = {Inflammaging},
keywords = {NLRP3 inflammasome},
keywords = {Mouse heart},
title = {Age and Chronodisruption in Mouse Heart: Effect of the NLRP3 Inflammasome and Melatonin Therapy},
doi = {10.3390/ijms23126846},
author = {Fernández Ortiz, Marisol and Sayed, Ramy K. A. and Román Montoya, Yolanda and Fernández Martínez, José and Ramírez Casas, Yolanda and Florido Ruiz, Javier and Rusanova Rusanova, Iryna and Escames Rosa, Germaine and Acuña Castroviejo, Darío},
}