Molecular Cardiology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99 - 34149, Trieste, Trieste, Italy.
Leibniz Institut für Analytische Wissenschaften-ISAS-e.V., Bunsen-Kirchhoff-Straße 11 | 44139 Dortmund, Germany, Dortmund, Germany.
Proteomics. 2020 Jun;20(11):e1900104. doi: 10.1002/pmic.201900104. Epub 2020 May 13.
Growth differentiation factor 11 (GDF11) is a TGF-β superfamily circulating factor that regulates cardiomyocyte size in rodents, sharing 90% amino acid sequence identity in the active domains with myostatin (GDF8)-the major determinant of skeletal muscle mass. Conflicting data on age-related changes in circulating levels have been reported mainly due to the lack of specific detection methods. More recently, liquid chromatography tandem mass spectrometry (LC-MS/MS) based assay showed that the circulating levels of GDF11 do not change significantly throughout human lifespan, but GDF8 levels decrease with aging in men. Here a novel detection method is demonstrated based on parallel reaction monitoring LC-MS/MS assay combined with immunoprecipitation to reliably distinguish GDF11 and GDF8 as well as determine their endogenous levels in mouse serum. The data indicate that both GDF11 and GDF8 circulating levels significantly decline with aging in female mice.
生长分化因子 11（GDF11）是转化生长因子-β超家族的循环因子，可调节啮齿动物心肌细胞的大小，其活性结构域与肌肉生长抑制素（GDF8）的同源性为 90%，而 GDF8 是骨骼肌质量的主要决定因素。由于缺乏特异性检测方法，主要是由于缺乏特异性检测方法，因此报告了循环水平与年龄相关的变化的矛盾数据。最近，基于液相色谱串联质谱（LC-MS/MS）的检测方法表明，GDF11 的循环水平在人类整个生命周期中没有明显变化，但 GDF8 的水平随着男性的衰老而降低。本文展示了一种新的检测方法，该方法基于平行反应监测 LC-MS/MS 检测与免疫沉淀相结合，可可靠地区分 GDF11 和 GDF8，并确定其在小鼠血清中的内源性水平。数据表明，随着雌性小鼠年龄的增长，GDF11 和 GDF8 的循环水平均显著下降。
