Schafer Marissa J, Atkinson Elizabeth J, Vanderboom Patrick M, Kotajarvi Brian, White Thomas A, Moore Matthew M, Bruce Charles J, Greason Kevin L, Suri Rakesh M, Khosla Sundeep, Miller Jordan D, Bergen H Robert, LeBrasseur Nathan K
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, Rochester, MN 55905, USA.
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Cell Metab. 2016 Jun 14;23(6):1207-1215. doi: 10.1016/j.cmet.2016.05.023.
Growth and differentiation factor 11 (GDF11) is a transforming growth factor β superfamily member with a controversial role in aging processes. We have developed a highly specific LC-MS/MS assay to quantify GDF11, resolved from its homolog, myostatin (MSTN), based on unique amino acid sequence features. Here, we demonstrate that MSTN, but not GDF11, declines in healthy men throughout aging. Neither GDF11 nor MSTN levels differ as a function of age in healthy women. In an independent cohort of older adults with severe aortic stenosis, we show that individuals with higher GDF11 were more likely to be frail and have diabetes or prior cardiac conditions. Following valve replacement surgery, higher GDF11 at surgical baseline was associated with rehospitalization and multiple adverse events. Cumulatively, our results show that GDF11 levels do not decline throughout aging but are associated with comorbidity, frailty, and greater operative risk in older adults with cardiovascular disease.
生长分化因子11（GDF11）是转化生长因子β超家族成员，在衰老过程中的作用存在争议。我们基于独特的氨基酸序列特征，开发了一种高度特异的液相色谱-串联质谱（LC-MS/MS）检测方法，用于定量从其同源物肌肉生长抑制素（MSTN）中分离出的GDF11。在此，我们证明，在健康男性的整个衰老过程中，MSTN水平下降，而GDF11水平未下降。在健康女性中，GDF11和MSTN水平均不会随年龄变化而有所不同。在一个患有严重主动脉瓣狭窄的老年人独立队列中，我们发现，GDF11水平较高的个体更有可能身体虚弱，患有糖尿病或有既往心脏疾病史。在瓣膜置换手术后，手术基线时较高的GDF11水平与再次住院及多种不良事件相关。总体而言，我们的结果表明，在患有心血管疾病的老年人中，GDF11水平在整个衰老过程中不会下降，而是与合并症、身体虚弱及更高的手术风险相关。
