MicroRNA-434-3p regulates age-related apoptosis through eIF5A1 in the skeletal muscle.
Increased activation of catabolic pathways, including apoptosis causes sarcopenia. However, the precise molecular mechanism that initiates apoptosis during aging is not well understood. Here, we report that aging alters miRNA expression profile in mouse skeletal muscle as evidenced by miRNA microarray and real-time PCR. We identified miR-434-3p as a highly downregulated miRNA in the skeletal muscle of aging mice. Myocytes transfected with miR-434-3p mimic prevents apoptosis induced by various apoptotic stimuli, and co-transfection of miR-434-3p antagomir abolishes the inhibitory role of miR-434-3p. We found that miR-434-3p inhibits apoptosis by targeting the eukaryotic translation initiation factor 5A1 (eIF5A1). Overexpression of miR-434-3p in myocytes reduces the loss of mitochondrial transmembrane potential, and activation of caspases-3, -8 and -9 by suppressing eIF5A1 in response to various apoptotic stimuli whereas inhibition of miR-434-3p reversed this scenario. Skeletal muscles from aging mice exhibit low levels of miR-434-3p and high levels of eIF5A1, suggesting a possible role for miR-434-3p in the initiation of apoptosis in aging muscle. Overall, our data identified for the first time that miR-434-3p is an anti-apoptotic miRNA that may be therapeutically useful for treating muscle atrophy in various pathophysiological conditions, including sarcopenia.
['Pardo|Patricia S|PS|', 'Hajira|Ameena|A|', 'Boriek|Aladin M|AM|', 'Mohamed|Junaith S|JS|']
D000375:Aging D000818:Animals D017209:Apoptosis D020169:Caspases D005786:Gene Expression Regulation D053078:Membrane Potential, Mitochondrial D051379:Mice D035683:MicroRNAs D032342:Muscle Cells D018482:Muscle, Skeletal D010448:Peptide Initiation Factors D016601:RNA-Binding Proteins
skeletal muscle sarcopenia aging mitochondria