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Research Paper|Volume 12, Issue 14|pp 13939—13957

Both ghrelin deletion and unacylated ghrelin overexpression preserve muscles in aging mice

Emanuela Agosti1,2, Marilisa De Feudis1, Elia Angelino3,4, Roberta Belli5, Maraiza Alves Teixeira1, Ivan Zaggia1, Edoardo Tamiso1, Tommaso Raiteri1, Andrea Scircoli1, Flavio L. Ronzoni6,7, Maurizio Muscaritoli5, Andrea Graziani3,4, Flavia Prodam2, Maurilio Sampaolesi6,8,9,12, Paola Costelli10,12, Elisabetta Ferraro11, Simone Reano1, Nicoletta Filigheddu1,12
  • 1Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
  • 2Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
  • 3Division of Oncology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milano, Italy
  • 4Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy
  • 5Department of Translational and Precision Medicine, Sapienza University, Rome, Italy
  • 6Department of Public Health, Experimental and Forensic Medicine, Institute of Human Anatomy, University of Pavia, Pavia, Italy
  • 7Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
  • 8Center for Health Technologies (CHT), University of Pavia, Pavia, Italy
  • 9Stem Cell Institute, KU Leuven, Leuven, Belgium
  • 10Department of Clinical and Biological Sciences, University of Torino, Turin, Italy
  • 11Division of Orthopaedics and Traumatology, Hospital “Maggiore della Carità”, Novara, Italy
  • 12Istituto Interuniversitario di Miologia (IIM)
* Equal contribution
Received: April 3, 2020Accepted: July 13, 2020Published: July 26, 2020

Copyright: © 2020 Agosti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Sarcopenia, the decline in muscle mass and functionality during aging, might arise from age-associated endocrine dysfunction. Ghrelin is a hormone circulating in both acylated (AG) and unacylated (UnAG) forms with anti-atrophic activity on skeletal muscle. Here, we show that not only lifelong overexpression of UnAG (Tg) in mice, but also the deletion of ghrelin gene (Ghrl KO) attenuated the age-associated muscle atrophy and functionality decline, as well as systemic inflammation. Yet, the aging of Tg and Ghrl KO mice occurs with different dynamics: while old Tg mice seem to preserve the characteristics of young animals, Ghrl KO mice features deteriorate with aging. However, young Ghrl KO mice show more favorable traits compared to WT animals that result, on the whole, in better performances in aged Ghrl KO animals. Treatment with pharmacological doses of UnAG improved muscle performance in old mice without modifying the feeding behavior, body weight, and adipose tissue mass. The antiatrophic effect on muscle mass did not correlate with modifications of protein catabolism. However, UnAG treatment induced a strong shift towards oxidative metabolism in muscle. Altogether, these data confirmed and expanded some of the previously reported findings and advocate for the design of UnAG analogs to treat sarcopenia.