The exerkine apelin reverses age-associated sarcopenia

Claire Vinel (1, 2) , Laura Lukjanenko (3) , Aurélie Batut (1, 2) , Simon Deleruyelle (1, 2) , Jean-Philippe Pradere (1, 2) , Sophie Le Gonidec (1, 2) , Alizee Dortignac (1, 2) , Nancy Geoffre (1, 2) , Ophelie Pereira (1, 2) , Sonia Karaz , Umji Lee (3) , Mylene Camus (4, 5) , Karima Chaoui (4, 5) , Etienne Mouisel (1, 2) , Anne Bigot (6) , Vincent Mouly (6) , Mathieu Vigneau (7) , Allan Pagano (8) , Angèle Chopard (8) , Fabien Pillard (1, 2) , Sophie Guyonnet (9) , Matteo Cesari (9) , Odile Burlet-Schiltz (4) , Marco Pahor (10) , Jerome N. Feige (3) , Bruno Vellas (9) , Philippe Valet (1, 2) , Cédric Dray (1, 2)

1 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
2 UT3 - Université Toulouse III - Paul Sabatier
3 Aging Dept, Nestle Inst Hlth Sci SA, Innovat Pk
4 IPBS - Institut de pharmacologie et de biologie structurale
5 CNRS - Centre National de la Recherche Scientifique
6 Centre de recherche en Myologie – U974 SU-INSERM
7 ITAV - Institut des Technologies Avancées en sciences du Vivant
8 DMEM - Dynamique Musculaire et Métabolisme
9 Gérontopôle
10 Coll Med, Inst Aging

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.

Mots clés: skeletal muscle; adipose tissue; regenerative capacity; physical activity; satellite cells

Domaines: Sciences du Vivant [q-bio]

Claire Vinel, Laura Lukjanenko, Aurélie Batut, Simon Deleruyelle, Jean-Philippe Pradere, et al.. The exerkine apelin reverses age-associated sarcopenia. Nature Medicine, 2018, 24 (9), pp.1360-1371. ⟨10.1038/s41591-018-0131-6⟩. ⟨hal-01918096⟩