ECE2020 Oral Communications Pituitary and Neuroendocrinology (7 abstracts)
Both ghrelin deletion and unacylated ghrelin overexpression preserve muscles in aging mice
Emanuela Agosti 1 , Marilisa De Feudis 2 , Elia Angelino 3 , Roberta Belli 4 , Maraiza Alves Teixeira 2 , Ivan Zaggia 2 , Tommaso Raiteri 2 , Andrea Scircoli 2 , Andrea Graziani 3 , Flavia Prodam 1 , Maurilio Sanpaolesi 5,6 , Paola Costelli 7 , Elisabetta Ferraro 8 , Simone Reano 2 & Nicoletta Filigheddu 2
1University of Piemonte Orientale, Department of Health Sciences, Novara, Italy; 2University of Piemonte Orientale, Department of Translational Medicine, Novara, Italy; 3San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Division of Oncology, Milano, Italy; 4Sapienza University of Rome,, Translational and Precision Medicine, Roma, Italy; 5University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Pavia, Italy; 6KU Leuven, Stem Cell Institute,, Leuven, Belgium; 7 University of Torino, Department of Clinical and Biological Sciences, Torino, Italy; 8Azienda Ospedaliero-Universitaria Maggiore della Carità, Division of Orthopaedics and Traumatology, Novara, Italy
Sarcopenia, the decline in muscle mass and functionality during aging, might arise from age-associated endocrine dysfunction. Indeed, muscle wasting follows the general decline in trophic hormones and the establishment of a chronic mild inflammatory status characteristic of aging. Ghrelin is a gastric hormone peptide circulating in both acylated (AG) and unacylated (UnAG) forms that have anti-atrophic activity on skeletal muscle. AG is the endogenous ligand of the growth hormone secretagogue receptor (GHSR-1a), and it is involved in metabolic regulation and energetic balance through induction of appetite, food intake, and adiposity. UnAG does not induce GH release and has no direct effects on food intake, but it shares with AG several biological activities on cell types lacking AG receptor. In particular, both AG and UnAG have direct biological activities on skeletal muscle, including promotion of myoblast differentiation and protection from atrophy, in all likelihood by activating a common receptor. Also, UnAG promotes muscle regeneration, stimulation of muscle satellite cell activity, and activates autophagy and mitophagy at higher extent than AG in muscles of nephrectomyzed mice. Age-dependent hypoghrelinemia could participate in the establishment of sarcopenia by facilitating the progression of muscle atrophy and limiting skeletal muscle regeneration capability. Here, we show that both the deletion of the ghrelin gene (Ghrl KO) and the lifelong overexpression of UnAG (Tg) in mice attenuated the age-associated decline in muscle mass and functionality, seen as larger myofiber areas, lower levels of Atrogin-1, an increased mitochondrial functionality compared to old WT animals. Also, both Ghrl KO and Tg animals displayed reduced systemic inflammation and maintenance of brown adipose tissue functionality. While old Tg mice apparently preserved the characteristics of young animals, Ghrl KO mice features deteriorate with aging. However, young Ghrl KO mice show more favorable features compared to WT animals that result, on the whole, in better performances in aged Ghrl KO mice. Altogether, the data collected suggest that, in Ghrl KO mice, it is the lack of AG the major determinant factor of their overall better conditions and advocate for the design of analogs to UnAG rather than AG to therapeutically treat sarcopenia in humans.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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