RT Journal Article T1 The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle A1 Sayed, Ramy KA A1 Fernández-Ortiz, Marisol A1 Fernández-Martínez, José A1 Aranda Martínez, Paula A1 Guerra-Librero, Ana A1 Rodríguez-Santana, César A1 de Haro, Tomás A1 Escames, Germaine A1 Acuña-Castroviejo, Darío A1 Rusanova, Iryna K1 microRNAs K1 Melatonin K1 NLRP3 inflammasome K1 NF-kB K1 Aging K1 Pro-caspase-1 K1 Caspase-3 K1 bcl-2 K1 Muscle fibers K1 Collagen K1 MicroARNs K1 Melatonina K1 Proteína con dominio pirina 3 de la familia NLR K1 FN-kappa B K1 Envejecimiento K1 Caspasa 1 K1 Caspasa 3 K1 Fibras Musculares Esqueléticas AB Muscular 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. PB MDPI YR 2021 FD 2021-03-27 LK http://hdl.handle.net/10668/4130 UL http://hdl.handle.net/10668/4130 LA en NO Sayed 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):524 DS RISalud RD Apr 7, 2025