K. E. Yarasheski*, S. Bhasin**, I. Sinha-Hikim**, J. Pak-Loduca*, N. F. Gonzalez-Cadavid**

*The Claude Pepper Older American's Independence Center, Division of Geriatrics and Gerontology. **Division of Metabolism, Endocrinology and Diabetes, Washington University School of Medicine, St. Louis, MO 63110. **Division of Endocrinology, Charles R. Drew University, Los Angeles, CA 90059. Correspondence:Kevin E.Yarasheski, PhD, Washington University Medical School, Division of Metabolism, Endocrinology and Diabetes, 660 South Euclid Avenue BOX 8127, St. Louis, MO 63110. Ph# 314-362-8173. FAX# 314-362-8188. e-mail:key@im.wustl.edu

BACKGROUND: Myostatin is a recently discovered member of the TGF-b superfamily of genes. It is expressed in skeletal muscle and believed to suppress muscle growth. Myostatin-null mice develop skeletal muscles that are 2-3x larger than wild type mice. Serum and intramuscular concentrations of myostatin-immunoreactive protein are increased in AIDS-muscle wasting and are inversely related with fat-free mass (FFM). OBJECTIVE: We hypothesized that increased expression of the myostatin gene is associated with the reduction in FFM and muscle mass typical of advancing age. DESIGN: A cross-sectional comparison of serum myostatin-immunoreactive protein levels, FFM and skeletal muscle mass in 19-35 yr old men and women (young), healthy 60-75 yr old men and women (middle-aged), and physically frail 76-92 yr old women. RESULTS: Muscle mass declined with advancing age in both men and women. Serum myostatin-immunoreactive protein levels were the highest in the 76-92 yr old women (P<0.05). Middle-aged men and women had higher serum myostatin levels than young men and women (P<0.05). FFM and muscle mass, corrected for height, were inversely correlated with serum myostatin-immunoreactive protein concentrations. CONCLUSIONS: These findings suggest that serum myostatin may be a biomarker of age-associated sarcopenia. They are consistent with the hypothesis that the human myostatin gene product is a suppressor of skeletal muscle growth in advancing age.

Keywords: Sarcopenia, transforming growth factor-b, muscle protein, cachexia, frailty.