Research Paper Volume 7, Issue 7 pp 500—512
Removal of growth hormone receptor (GHR) in muscle of male mice replicates some of the health benefits seen in global GHR−/− mice
- 1 Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA
- 2 Department of Specialty Medicine, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA
- 3 School of Applied Health Sciences and Wellness, Ohio University, Athens, OH 45701, USA
- 4 Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA
- 5 The Barshop Institute for Longevity and Aging Studies, San Antonio, Department of Pathology, The University of Texas Health Science Center at San Antonio, Research Service, Audie L. Murphy VA Hospital (STVHCS), San Antonio, TX 78229, USA
- 6 Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA
- 7 Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
- 8 College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, 32827, USA
- 9 Department of Head and Neck Surgery, The Greater Poland Cancer Centre, Poznan, 61-866, Poland
- 10 Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI 48109, USA
Received: June 2, 2015 Accepted: June 20, 2015 Published: June 29, 2015
https://doi.org/10.18632/aging.100766How to Cite
Abstract
Global disruption of the GH receptor in mice (GHR−/−) produces a large and reproducible extension in lifespan. Since lack of GH action in muscle resulting in improved glucose homeostasis is potentially a mechanism by which GHR−/− mice are long-lived, and since no information on muscle-specific GHR disruption in females is available, we generated and characterized a line of muscle-specific GHR disrupted (MuGHRKO) mice. As expected, male MuGHRKO mice had improved fasting blood glucose, insulin, c-peptide, and glucose tolerance. In contrast, female MuGHRKO mice exhibited normal glucose, insulin, and glucose tolerance. Body weight was mildly but significantly altered in opposite directions in males (decreased) and females (increased) compared to controls. Grip strength and treadmill endurance were unchanged with advanced age in both sexes, suggesting that the direct action of GH on muscle has minimal effect on age-related musculoskeletal frailty. Longevity was unchanged in both sexes at Ohio University and significantly increased for males at University of Michigan. These data suggest that removal of GHR in muscle of male MuGHRKO mice replicates some of the health benefits seen in global GHR−/− mice including improvements to glucose homeostasis and smaller body weight in males, which may explain the trends observed in lifespan.