title: Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: insights using a new mass spectrometry-based assay.
abstract: BACKGROUND
  Myostatin is a protein synthesized and secreted by skeletal muscle that negatively regulates muscle mass. The extent to which circulating myostatin levels change in the context of aging is controversial, largely due to methodological barriers.
  
  
  METHODS
  We developed a specific and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay to measure concentrations of myostatin and two of its key inhibitors, follistatin-related gene (FLRG) protein and growth and serum protein-1 (GASP-1) in 80 younger (<40 years), 80 older (>65 years), and 80 sarcopenic older women and men.
  
  
  RESULTS
  Older women had 34 % higher circulating concentrations of myostatin than younger women. Per unit of lean mass, both older and sarcopenic older women had >23 % higher myostatin levels than younger women. By contrast, younger men had higher myostatin concentrations than older men with and without sarcopenia. Younger men had approximately twofold higher concentrations of myostatin than younger women; however, older women and sarcopenic older women had significantly higher relative myostatin levels than the corresponding groups of men. In both sexes, sarcopenic older subjects had the highest concentrations of FLRG. Circulating concentrations of myostatin exhibited positive, but not robust, correlations with relative muscle mass in both sexes.
  
  
  CONCLUSIONS
  Our data suggest that myostatin may contribute to the higher prevalence of sarcopenia in women but acts as a homeostatic regulator of muscle mass in men. Moreover, this new LC-MS/MS-based approach offers a means to determine the extent to which myostatin serves as a biomarker of muscle health in diverse conditions of muscle loss and deterioration.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905 USA.|Medical Genome Facility-Proteomics Core, Mayo Clinic College of Medicine, Rochester, MN 55905 USA.
authors.forename: H Robert
authors.initials: HR
authors.lastname: Bergen
authors.affiliation: Division of Endocrinology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905 USA.|Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Rochester, MN 55905 USA.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Farr
authors.affiliation: Medical Genome Facility-Proteomics Core, Mayo Clinic College of Medicine, Rochester, MN 55905 USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Vanderboom
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905 USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Atkinson
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Rochester, MN 55905 USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: White
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905 USA.
authors.forename: Ravinder J
authors.initials: RJ
authors.lastname: Singh
authors.affiliation: Division of Endocrinology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905 USA.|Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Rochester, MN 55905 USA.
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Rochester, MN 55905 USA.|Department of Physical Medicine and Rehabilitation, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 USA.
authors.forename: Nathan K
authors.initials: NK
authors.lastname: LeBrasseur
keywords: Aging; Body composition; Myostatin; Sarcopenia; Skeletal muscle mass; Strength