Protective effects of ghrelin on fasting-induced muscle atrophy in aging mice

Chia Shan Wu, Qiong Wei, Hongying Wang, Da Mi Kim, Miriam Balderas, Guoyao Wu, John Lawler, Stephen Safe, Shaodong Guo, Sridevi Devaraj, Zheng Chen, Yuxiang Sun

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)621-630
Number of pages10
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number4
StatePublished - Mar 9 2020


  • Acyl-ghrelin
  • Gut microbiota
  • Sarcopenia
  • Unacylated ghrelin
  • Ghrelin/deficiency
  • Mitochondria, Muscle/metabolism
  • Adiposity/genetics
  • Aging/genetics
  • Sarcopenia/etiology
  • Mice, Inbred C57BL
  • Gastrointestinal Microbiome
  • Male
  • Fasting/adverse effects
  • Mice, Knockout
  • Muscular Atrophy/pathology
  • Motor Activity/genetics
  • Muscle, Skeletal/pathology
  • Animals
  • Mice
  • Acylation
  • Disease Models, Animal

ASJC Scopus subject areas

  • Medicine(all)


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