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- Title
Age Trends in Growth and Differentiation Factor-11 and Myostatin Levels in Healthy Men, and Differential Response to Testosterone, Measured Using Liquid Chromatography-Tandem Mass Spectrometry.
- Authors
Peng, Liming; Gagliano-Jucá, Thiago; Pencina, Karol M; Krishnan, Srinivasan; Li, Zhuoying; Tracy, Russell P; Jasuja, Ravi; Bhasin, Shalender
- Abstract
<bold>Background: </bold>Growth and differentiation factor (GDF)-11 controls embryonic development and has been proposed as an antiaging factor. GDF-8 (myostatin) inhibits skeletal muscle growth. Difficulties in accurately measuring circulating GDF-11 and GDF-8 have generated controversy.<bold>Methods: </bold>We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous measurement of circulating GDF-8 and GDF-11 that employs denaturation, reduction, and alkylation; cation-exchange solid-phase extraction; tryptic digestion; followed by separation and quantification using 2 signature peptides for multiple reaction monitoring and C-terminal [13C615N4]-Arg peptides as internal standards. We evaluated age trends in serum GDF-11 and GDF-8 concentrations in community-dwelling healthy men, 19 years or older, and determined the effects of graded testosterone doses on GDF-8 and GDF-11 concentrations in healthy men in a randomized trial.<bold>Results: </bold>The assay demonstrated linearity over a wide range, lower limit of quantitation 0.5 ng/mL for both proteins, and excellent precision, accuracy, and specificity (no detectable cross-reactivity of GDF-8 in GDF-11 assay or of GDF-11 in GDF-8 assay). Mean ± SD (median ± 1QR) GDF-8 and GDF-11 levels in healthy community-dwelling men, 19 years and older, were 7.2 ± 1.9 (6.8 ± 1.4) ng/mL. Neither GDF-8 nor GDF-11 levels were related to age or body composition. Testosterone treatment significantly increased serum GDF-8 but not GDF-11 levels.<bold>Conclusions: </bold>The LC-MS/MS method for the simultaneous measurement of circulating total GDF-8 and GDF-11 demonstrates the characteristics of a valid assay. Testosterone treatment increased GDF-8 levels, but not GDF-11. Increase in GDF-8 levels by testosterone treatment, which increased muscle mass, suggests that GDF-8 acts as a chalone to restrain muscle growth.
- Subjects
LIQUID chromatography-mass spectrometry; MYOSTATIN; TESTOSTERONE; MUSCLE growth; SOLID phase extraction; ANDROGEN receptors; GROWTH factors; LIQUID chromatography; MASS spectrometry; RESEARCH funding; BLOOD coagulation factors
- Publication
Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2022, Vol 77, Issue 4, p763
- ISSN
1079-5006
- Publication type
journal article
- DOI
10.1093/gerona/glab146