title: Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice.
abstract: Sarcopenia, or skeletal muscle atrophy, is a debilitating comorbidity of many physiological and pathophysiological processes, including normal aging. There are no approved therapies for sarcopenia, but the antihypertrophic myokine myostatin is a potential therapeutic target. Here, we show that treatment of young and old mice with an anti-myostatin antibody (ATA 842) for 4 wk increased muscle mass and muscle strength in both groups. Furthermore, ATA 842 treatment also increased insulin-stimulated whole body glucose metabolism in old mice, which could be attributed to increased insulin-stimulated skeletal muscle glucose uptake as measured by a hyperinsulinemic-euglycemic clamp. Taken together, these studies provide support for pharmacological inhibition of myostatin as a potential therapeutic approach for age-related sarcopenia and metabolic disease.
authors: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;
authors: João-Paulo G
authors: JP
authors: Camporez
authors: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520;
authors: Max C
authors: MC
authors: Petersen
authors: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;
authors: Abulizi
authors: A
authors: Abudukadier
authors: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;
authors: Gabriela V
authors: GV
authors: Moreira
authors: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;
authors: Michael J
authors: MJ
authors: Jurczak
authors: Atara Biotherapeutics, Westlake Village, CA 91363;
authors: Glenn
authors: G
authors: Friedman
authors: Atara Biotherapeutics, Westlake Village, CA 91363;
authors: Christopher M
authors: CM
authors: Haqq
authors: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;
authors: Kitt Falk
authors: KF
authors: Petersen
authors: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520 gerald.shulman@yale.edu.
authors: Gerald I
authors: GI
authors: Shulman
mesh_terms: D000375:Aging / Q000276:immunology / Q000473:pathology / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004734:Energy Metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D053580:Muscle Strength / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology*; D055435:Myostatin / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D055948:Sarcopenia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; C525911:MSTN protein, human; D055435:Myostatin
keywords: aging; insulin resistance; muscle mass; myostatin; sarcopenia