Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice

被引:168
作者
Camporez, Joao-Paulo G. [1 ]
Petersen, Max C. [1 ,2 ]
Abudukadier, Abulizi [1 ]
Moreira, Gabriela V. [1 ]
Jurczak, Michael J. [3 ]
Friedman, Glenn [4 ]
Haqq, Christopher M. [4 ]
Petersen, Kitt Falk [1 ]
Shulman, Gerald I. [1 ,2 ,5 ]
机构
[1] Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, 333 Cedar St, New Haven, CT 06520 USA
[3] Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, 930 Scaife Hall, Pittsburgh, PA 15261 USA
[4] Atara Biotherapeut, Westlake Village, CA 91363 USA
[5] Yale Univ, Sch Med, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06520 USA
基金
美国国家卫生研究院;
关键词
aging; myostatin; muscle mass; insulin resistance; sarcopenia; FAT MASS; TRANSGENIC EXPRESSION; DEFICIENT MICE; INHIBITION; SARCOPENIA; RESISTANCE; GENE; DIET; EPIDEMIOLOGY; HYPERTROPHY;
D O I
10.1073/pnas.1525795113
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
收藏
页码:2212 / 2217
页数:6
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