Thrifty Hormone Ghrelin: The Secret of Aging Muscularly

Thrifty Hormone Ghrelin: The Secret of Aging Muscularly
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节俭激素胃饥饿素:肌肉衰老的秘密

DOI:
10.35248/2329-8847.20.s3.005
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发表时间:
2020
期刊:
Journal of aging science
影响因子:
--
通讯作者:
Yuxiang Sun
Yuxiang Sun
中科院分区:
--
文献类型:
--
作者:
Yuxiang Sun

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肌肉减少症是一种使人衰弱的肌肉消耗性疾病,是衰老时虚弱和残疾的主要原因。Ghrelin(aka acylated ghrelin,AG)是一种循环肽激素,在Ser 3上具有独特的辛酰化。AG通过其受体生长激素促分泌素受体(GHS-R)诱导生长激素(GH)分泌,增加食物摄入,并促进肥胖和胰岛素抵抗。与AG不同,未酰化的生长素释放肽(UAG)是由相同的生长素释放肽基因产生的肽,其氨基酸序列与AG相同,但没有辛酰化修饰,因此UAG不激活GHS-R。有趣的是,AG和UAG都被证明可以促进肌肉C2 C12细胞的分化和融合,调节肌管中的代谢和线粒体信号通路,并减弱禁食或去神经诱导的肌肉萎缩。此外,还表明生长素释放肽基因缺陷增加了衰老小鼠对禁食诱导的肌肉损失的脆弱性,并且AG和UAG有效地防止衰老小鼠的肌肉萎缩。由于UAG不与GHS-R结合,因此它不具有AG那样的GH释放升高和肥胖增加的不良副作用。综上所述,UAG在保护肌肉免受衰老中的肌肉萎缩方面具有令人印象深刻的抗萎缩作用,其具有成为诸如肌肉减少症的肌肉消耗性疾病的独特和上级治疗候选者的潜力。
Sarcopenia is a debilitating muscle-wasting disease that is the major cause of frailty and disability in aging. Ghrelin (aka acylated ghrelin, AG) is a circulating peptide hormone with an unique octanoylation on Ser3. AG induces growth hormone (GH) secretion, increases food intake, and promotes adiposity and insulin resistance via its receptor, Growth Hormone Secretagogue Receptor (GHS-R). Unlike AG, unacylated ghrelin (UAG) is a peptide generated from the same ghrelin gene with amino acid sequence identical to AG but without the octanoylation modification, so UAG does not activate GHS-R. Intriguingly, both AG and UAG have been shown to promote differentiation and fusion of muscle C2C12 cells, regulate metabolic and mitochondrial signaling pathways in myotubes, and attenuate fasting- or denervation-induced muscle atrophy. Furthermore, it has also been shown that ghrelin gene deficiency increases vulnerability to fasting-induced muscle loss in aging mice, and AG and UAG effectively protects against muscle atrophy of aging mice. Because UAG doesn’t bind to GHS-R, it doesn’t have the undesired side-effects of elevated GH-release and increased obesity as AG. In summary, UAG has an impressive anti-atrophic effect in muscle protecting against muscle atrophy in aging, it has potential to be a unique and superior therapeutic candidate for muscle-wasting diseases such as sarcopenia.
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