The exerkine apelin reverses age-associated sarcopenia
2018
Vinel, Claire | Lukjanenko, Laura | Batut, Aurélie | Deleruyelle, Simon | Pradere, Jean-Philippe | Le Gonidec, Sophie | Dortignac, Alizee | Geoffre, Nancy | Pereira, Ophelie | Karaz, Sonia | Lee, Umji | Camus, Mylene | Chaoui, Karima | Mouisel, Etienne | Bigot, Anne | Mouly, Vincent | Vigneau, Mathieu | Pagano, Allan | Chopard, Angèle | Pillard, Fabien | Guyonnet, Sophie | Cesari, Matteo | Burlet-Schiltz, Odile | Pahor, Marco | Feige, Jerome N. | Vellas, Bruno | Valet, Philippe | Dray, Cédric | Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT) | Aging Dept, Nestle Inst Hlth Sci SA, Innovat Pk ; Ecole Polytechnique Fédérale de Lausanne (EPFL) | Institut de pharmacologie et de biologie structurale (IPBS) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS) | Centre National de la Recherche Scientifique (CNRS) | Centre de recherche en Myologie – U974 SU-INSERM ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU) | Institut des Technologies Avancées en sciences du Vivant (ITAV) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS) | Dynamique Musculaire et Métabolisme (DMEM) ; Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM) | Gérontopôle ; Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse) | Coll Med, Inst Aging ; University of Florida [Gainesville] (UF) | ANR-16-CE18-0022,DIVA,Visualization de l'amylin avec des sondes métalliques pour une imagerie du diabète(2016)
Sarcopenia, the degenerative loss of skeletal muscle mass, quality and strength, lacks early diagnostic tools and new therapeutic strategies to prevent the frailty-to-disability transition often responsible for the medical institutionalization of elderly individuals. Herein we report that production of the endogenous peptide apelin, induced by muscle contraction, is reduced in an age-dependent manner in humans and rodents and is positively associated with the beneficial effects of exercise in older persons. Mice deficient in either apelin or its receptor (APLNR) presented dramatic alterations in muscle function with increasing age. Various strategies that restored apelin signaling during aging further demonstrated that this peptide considerably enhanced muscle function by triggering mitochondriogenesis, autophagy and anti-inflammatory pathways in myofibers as well as enhancing the regenerative capacity by targeting muscle stem cells. Taken together, these findings revealed positive regulatory feedback between physical activity, apelin and muscle function and identified apelin both as a tool for diagnosis of early sarcopenia and as the target of an innovative pharmacological strategy to prevent age-associated muscle weakness and restore physical autonomy.
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