Sayed, Ramy KAFernández-Ortiz, MarisolFernández-Martínez, JoséAranda Martínez, PaulaGuerra-Librero, AnaRodríguez-Santana, Césarde Haro, TomásEscames, GermaineAcuña-Castroviejo, DaríoRusanova, Iryna2022-09-232022-09-232021-03-27Sayed RK, Fernández-Ortiz M, Fernández-Martínez J, Aranda Martínez P, Guerra-Librero A, Rodríguez-Santana C, et al. The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle. Antioxidants (Basel). 2021 Mar 27;10(4):524http://hdl.handle.net/10668/4130Muscular aging is a complex process and underlying physiological mechanisms are not fully clear. In recent years, the participation of the NF-kB pathway and the NLRP3 inflammasome in the chronic inflammation process that accompanies the skeletal muscle's aging has been confirmed. microRNAs (miRs) form part of a gene regulatory machinery, and they control numerous biological processes including inflammatory pathways. In this work, we studied the expression of four miRs; three of them are considered as inflammatory-related miRs (miR-21, miR-146a, and miR-223), and miR-483, which is related to the regulation of melatonin synthesis, among other targets. To investigate the changes of miRs expression in muscle along aging, the impact of inflammation, and the role of melatonin in aged skeletal muscle, we used the gastrocnemius muscle of wild type (WT) and NLRP3-knockout (NLRP3-) mice of 3, 12, and 24 months-old, with and without melatonin supplementation. The expression of miRs and pro-caspase-1, caspase-3, pro-IL-1β, bax, bcl-2, and p53, was investigated by qRT-PCR analysis. Histological examination of the gastrocnemius muscle was also done. The results showed that age increased the expression of miR-21 (p < 0.01), miR-146a, and miR-223 (p < 0.05, for both miRs) in WT mice, whereas the 24-months-old mutant mice revealed decline of miR-21 and miR-223 (p < 0.05), compared to WT age. The lack of NLRP3 inflammasome also improved the skeletal muscle fibers arrangement and reduced the collagen deposits compared with WT muscle during aging. For the first time, we showed that melatonin significantly reduced the expression of miR-21, miR-146a, and miR-223 (p < 0.05 for all ones, and p < 0.01 for miR-21 at 24 months old) in aged WT mice, increased miR-223 in NLRP3- mice (p < 0.05), and induced miR-483 expression in both mice strains, this increase being significant at 24 months of age.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/microRNAsMelatoninNLRP3 inflammasomeNF-kBAgingPro-caspase-1Caspase-3bcl-2Muscle fibersCollagenMicroARNsMelatoninaProteína con dominio pirina 3 de la familia NLRFN-kappa BEnvejecimientoCaspasa 1Caspasa 3Fibras Musculares EsqueléticasMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Multiprotein Complexes::InflammasomesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins::Caspases::Caspases, Initiator::Caspase 1Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::MelatoninMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::NF-kappa BMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins::Caspases::Caspases, Effector::Caspase 3Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor Proteins::Tumor Suppressor Protein p53Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins::Proto-Oncogene Proteins c-bcl-2::bcl-2-Associated X ProteinMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Antisense::MicroRNAsMedical Subject Headings::Anatomy::Musculoskeletal System::Muscles::Muscle, SkeletalMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::InflammationMedical Subject javascript:void(null);Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Scleroproteins::Extracellular Matrix Proteins::CollagenMedical Subject Headings::Anatomy::Tissues::Muscles::Muscle, Striated::Muscle, Skeletal::Muscle Fibers, SkeletalMedical Subject Headings::Phenomena and Processes::Biological PhenomenaMedical Subject Headings::Technology and Food and Beverages::Food and Beverages::Food::Dietary SupplementsMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-1Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reactionresearch article33801675open access10.3390/antiox100405242076-3921PMC8066875