Sarcopenia is the aging-associated progressive loss of skeletal muscle; however, the pathogenic mechanism of sarcopenia is not clear. The orexigenic hormone ghrelin stimulates growth hormone secretion, increases food intake, and promotes adiposity. Here we showed that fasting-induced muscle loss was exacerbated in old ghrelin-null (Ghrl-/-) mice, exhibiting decreased expression of myogenic regulator MyoD and increased expression of protein degradation marker MuRF1, as well as altered mitochondrial function. Moreover, acylated ghrelin and unacylated ghrelin treatments significantly increased mitochondrial respiration capacity in muscle C2C12 cells. Consistently, acylated ghrelin and unacylated ghrelin treatments effectively increased myogenic genes and decreased degradation genes in the muscle in fasted old Ghrl-/- mice, possibly by stimulating insulin and adenosine monophosphate-activated protein kinase pathways. Furthermore, Ghrl-/- mice showed a profile of pro-inflammatory gut microbiota, exhibiting reduced butyrate-producing bacteria Roseburia and ClostridiumXIVb. Collectively, our results showed that ghrelin has a major role in the maintenance of aging muscle via both muscle-intrinsic and -extrinsic mechanisms. Acylated ghrelin and unacylated ghrelin enhanced muscle anabolism and exerted protective effects for muscle atrophy. Because unacylated ghrelin is devoid of the obesogenic side effect seen with acylated ghrelin, it represents an attractive therapeutic option for sarcopenia.

中文翻译：

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Ghrelin 对衰老小鼠禁食引起的肌肉萎缩的保护作用。

肌肉减少症是与衰老相关的骨骼肌进行性丧失；然而，肌肉减少症的发病机制尚不清楚。促食激素生长素释放肽刺激生长激素分泌，增加食物摄入量，并促进肥胖。在这里，我们发现禁食诱导的肌肉损失在老生长素释放肽无效 (Ghrl-/-) 小鼠中加剧，表现出生肌调节因子 MyoD 的表达减少和蛋白质降解标记 MuRF1 的表达增加，以及线粒体功能改变。此外，酰化生长素释放肽和未酰化生长素释放肽处理显着增加了肌肉 C2C12 细胞中的线粒体呼吸能力。一致地，酰化生长素释放肽和未酰化生长素释放肽治疗有效地增加了禁食的老年 Ghrl-/- 小鼠肌肉中的生肌基因并减少了降解基因，可能通过刺激胰岛素和腺苷一磷酸激活蛋白激酶通路。此外，Ghrl-/- 小鼠显示出促炎性肠道微生物群的概况，表现出减少的产丁酸盐细菌 Roseburia 和 ClostridiumXIVb。总的来说，我们的结果表明，生长素释放肽通过肌肉内在和外在机制在维持老化肌肉方面发挥着重要作用。酰化生长素释放肽和未酰化生长素释放肽增强肌肉合成代谢并对肌肉萎缩发挥保护作用。由于未酰化生长素释放肽没有酰化生长素释放肽所见的致肥胖副作用，因此它代表了肌肉减少症的一种有吸引力的治疗选择。表现出减少的产丁酸盐细菌 Roseburia 和 ClostridiumXIVb。总的来说，我们的结果表明，生长素释放肽通过肌肉内在和外在机制在维持老化肌肉方面发挥着重要作用。酰化生长素释放肽和未酰化生长素释放肽增强肌肉合成代谢并对肌肉萎缩发挥保护作用。由于未酰化生长素释放肽没有酰化生长素释放肽所见的致肥胖副作用，因此它代表了肌肉减少症的一种有吸引力的治疗选择。表现出减少的产丁酸盐细菌 Roseburia 和 ClostridiumXIVb。总的来说，我们的结果表明，生长素释放肽通过肌肉内在和外在机制在维持老化肌肉方面发挥着重要作用。酰化生长素释放肽和未酰化生长素释放肽增强肌肉合成代谢并对肌肉萎缩发挥保护作用。由于未酰化生长素释放肽没有酰化生长素释放肽所见的致肥胖副作用，因此它代表了肌肉减少症的一种有吸引力的治疗选择。