Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: Insights using a new mass spectrometry-based assay

Harold Robert (Bob) III Bergen, Joshua Farr, Patrick M. Vanderboom, Elizabeth J. Atkinson, Thomas A. White, Ravinder Jit Singh, Sundeep Khosla, Nathan K LeBrasseur

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34 Citations (Scopus)

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.

Original languageEnglish (US)
Article number21
JournalSkeletal Muscle
Volume5
Issue number1
DOIs
StatePublished - Jul 15 2015

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Myostatin
Sarcopenia
Mass Spectrometry
Muscles
Follistatin-Related Proteins
Follistatin
Tandem Mass Spectrometry
Liquid Chromatography
Blood Proteins
Skeletal Muscle
Proteins

Keywords

  • Aging
  • Body composition
  • Myostatin
  • Sarcopenia
  • Skeletal muscle mass
  • Strength

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology

Cite this

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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.",
keywords = "Aging, Body composition, Myostatin, Sarcopenia, Skeletal muscle mass, Strength",
author = "Bergen, {Harold Robert (Bob) III} and Joshua Farr and Vanderboom, {Patrick M.} and Atkinson, {Elizabeth J.} and White, {Thomas A.} and Singh, {Ravinder Jit} and Sundeep Khosla and LeBrasseur, {Nathan K}",
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T1 - Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass

T2 - Insights using a new mass spectrometry-based assay

AU - Bergen, Harold Robert (Bob) III

AU - Farr, Joshua

AU - Vanderboom, Patrick M.

AU - Atkinson, Elizabeth J.

AU - White, Thomas A.

AU - Singh, Ravinder Jit

AU - Khosla, Sundeep

AU - LeBrasseur, Nathan K

PY - 2015/7/15

Y1 - 2015/7/15

N2 - 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.

AB - 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.

KW - Aging

KW - Body composition

KW - Myostatin

KW - Sarcopenia

KW - Skeletal muscle mass

KW - Strength

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