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J Gerontol A Biol Sci Med Sci. 2018 Nov 8. doi: 10.1093/gerona/gly256. [Epub ahead of print]

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

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Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA.
USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Division of Endocrinology, Zhongda hospital, Southeast University, Nanjing, Jiangsu Province, People's Republic of China.
Laboratory of Lipid & Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Pathology and Immunology, Baylor College of Medicine; Houston, TX, USA.
Department of Animal Science, Texas A&M University, College Station, TX.
Department of Health & Kinesiology, Texas A&M University, College Station, TX.
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas.
The University of Texas Health Science Center at Houston, TX, USA.


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 (AG) and unacylated ghrelin (UAG) treatments significantly increased mitochondrial respiration capacity in muscle C2C12 cells. Consistently, AG and UAG treatments effectively increased myogenic genes and decreased degradation genes in the muscle in fasted old Ghrl-/- mice, possibly by stimulating insulin and AMPK 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. AG and UAG enhanced muscle anabolism and exerted protective effects for muscle atrophy. Since UAG is devoid of the obesogenic side effect seen with AG, it represents an attractive therapeutic option for sarcopenia.


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