Myostatin--the holy grail for muscle, bone, and fat?
Myostatin, a member of the transforming growth factor beta (TGF-β) superfamily, was first described in 1997. Since then, myostatin has gained growing attention because of the discovery that myostatin inhibition leads to muscle mass accrual. Myostatin not only plays a key role in muscle homeostasis, but also affects fat and bone. This review will focus on the impact of myostatin and its inhibition on muscle mass/function, adipose tissue and bone density/geometry in humans. Although existing data are sparse, myostatin inhibition leads to increased lean mass and 1 study found a decrease in fat mass and increase in bone formation. In addition, myostatin levels are increased in sarcopenia, cachexia and bed rest whereas they are increased after resistance training, suggesting physiological regulatory of myostatin. Increased myostatin levels have also been found in obesity and levels decrease after weight loss from caloric restriction. Knowledge on the relationship of myostatin with bone is largely based on animal data where elevated myostatin levels lead to decreased BMD and myostatin inhibition improved BMD. In summary, myostatin appears to be a key factor in the integrated physiology of muscle, fat, and bone. It is unclear whether myostatin directly affects fat and bone, or indirectly via muscle. Whether via direct or indirect effects, myostatin inhibition appears to increase muscle and bone mass and decrease fat tissue-a combination that truly appears to be a holy grail. However, at this time, human data for both efficacy and safety are extremely limited. Moreover, whether increased muscle mass also leads to improved function remains to be determined. Ultimately potential beneficial effects of myostatin inhibition will need to be determined based on hard outcomes such as falls and fractures.
Division of Geriatrics and Gerontology, University of Wisconsin Osteoporosis Clinical Research Program, UW Madison, 2870 University Ave, Suite 100, Madison, WI, 53705, USA, bbuehring@medicine.wisc.edu.
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Buehring
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Binkley
D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D006801:Humans; D009132:Muscles / Q000502:physiology*; D055435:Myostatin / Q000037:antagonists & inhibitors / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology; D010024:Osteoporosis / Q000503:physiopathology; D055948:Sarcopenia / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology
D055435:Myostatin