A common characteristic of aging is defective regeneration of skeletal muscle. The molecular pathways underlying age‐related decline in muscle regenerative potential remain elusive. microRNAs are novel gene regulators controlling development and homeostasis and the regeneration of most tissues, including skeletal muscle. Here, we use satellite cells and primary myoblasts from mice and humans and an in vitro regeneration model, to show that disrupted expression of microRNA‐143‐3p and its target gene, Igfbp5, plays an important role in muscle regeneration in vitro. We identified miR‐143 as a regulator of the insulin growth factor‐binding protein 5 (Igfbp5) in primary myoblasts and show that the expression of miR‐143 and its target gene is disrupted in satellite cells from old mice. Moreover, we show that downregulation of miR‐143 during aging may act as a compensatory mechanism aiming at improving myogenesis efficiency; however, concomitant upregulation of miR‐143 target gene, Igfbp5, is associated with increased cell senescence, thus affecting myogenesis. Our data demonstrate that dysregulation of miR‐143‐3p:Igfbp5 interactions in satellite cells with age may be responsible for age‐related changes in satellite cell function.

中文翻译：

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miR-143-3p:Igfbp5 相互作用的年龄相关变化影响肌肉再生。

衰老的一个共同特征是骨骼肌的再生缺陷。与年龄相关的肌肉再生潜力下降的分子途径仍然难以捉摸。microRNAs 是控制发育和体内平衡以及大多数组织（包括骨骼肌）再生的新型基因调节剂。在这里，我们使用来自小鼠和人类的卫星细胞和原代成肌细胞以及体外再生模型，证明 microRNA-143-3p 及其靶基因 Igfbp5 的表达中断在体外肌肉再生中起重要作用. 我们将 miR-143 鉴定为原代成肌细胞中胰岛素生长因子结合蛋白 5 (Igfbp5) 的调节剂，并表明 miR-143 及其靶基因的表达在老年小鼠的卫星细胞中被破坏。此外，我们表明衰老过程中 miR-143 的下调可能作为一种补偿机制，旨在提高肌生成效率；然而，伴随的 miR-143 靶基因 Igfbp5 的上调与细胞衰老增加有关，从而影响肌生成。我们的数据表明，随着年龄的增长，卫星细胞中 miR-143-3p:Igfbp5 相互作用的失调可能是卫星细胞功能与年龄相关的变化的原因。