Xia Ke, Trasatti Hannah, Wymer James P, Colón Wilfredo
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY, 12180, USA.
Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY, 12180, USA.
Age (Dordr). 2016 Jun;38(3):56. doi: 10.1007/s11357-016-9919-9. Epub 2016 May 14.
Proteins that misfold into hyper-stable/degradation-resistant species during aging may accumulate and disrupt protein homeostasis (i.e., proteostasis), thereby posing a survival risk to any organism. Using the method diagonal two-dimensional (D2D) SDS-PAGE, which separates hyper-stable SDS-resistant proteins at a proteomics level, we analyzed the plasma of healthy young (<30 years) and older (60-80 years) adults. We discovered the presence of soluble SDS-resistant protein aggregates in the plasma of older adults, but found significantly lower levels in the plasma of young adults. We identified the inflammation-related chaperone protein haptoglobin as the main component of the hyper-stable aggregates. This observation is consistent with the growing link between accumulations of protein aggregates and aging across many organisms. It is plausible higher amounts of SDS-resistant protein aggregates in the plasma of older adults may reflect a compromise in proteostasis that may potentially indicate cellular aging and/or disease risk. The results of this study have implications for further understanding the link between aging and the accumulation of protein aggregates, as well as potential for the development of aging-related biomarkers. More broadly, this novel application of D2D SDS-PAGE may be used to identify, quantify, and characterize the degradation-resistant protein aggregates in human plasma or any biological system.
在衰老过程中错误折叠成超稳定/抗降解形式的蛋白质可能会积累并破坏蛋白质稳态（即蛋白质动态平衡），从而对任何生物体构成生存风险。我们使用对角线二维（D2D）SDS-PAGE方法，该方法在蛋白质组学水平上分离超稳定的抗SDS蛋白质，分析了健康年轻人（<30岁）和老年人（60-80岁）的血浆。我们在老年人的血浆中发现了可溶性抗SDS蛋白质聚集体的存在，但在年轻人的血浆中发现其水平显著较低。我们确定炎症相关伴侣蛋白触珠蛋白是超稳定聚集体的主要成分。这一观察结果与许多生物体中蛋白质聚集体积累与衰老之间日益紧密的联系相一致。老年人血浆中较高含量的抗SDS蛋白质聚集体可能反映了蛋白质稳态的受损，这可能潜在地表明细胞衰老和/或疾病风险，这似乎是合理的。这项研究的结果对于进一步理解衰老与蛋白质聚集体积累之间的联系以及开发与衰老相关生物标志物的潜力具有重要意义。更广泛地说，D2D SDS-PAGE的这种新应用可用于鉴定、定量和表征人血浆或任何生物系统中抗降解的蛋白质聚集体。
