Proteomic Pipelines for the Quantification of Abundance and Turnover of Post-Translationally Modified Proteins in Aging Studies

我们已经朝着第一个目标--在天际蛋白质组学平台内开发一个软件工具--取得了重大进展。我们与Skyline核心开发团队(西雅图华盛顿大学的Michael MacCoss和Brendan MacLean)合作开发了一个软件工具，该工具现已在Skyline外部工具商店提供。这篇手稿现已发表在《蛋白质组研究》杂志上。 为了我们的第二个目标，我们与明尼苏达州罗切斯特市梅奥诊所的克里斯托弗·亚当斯博士合作，利用这一工具进行了第一次小鼠研究，以确定哪些蛋白质在肌肉萎缩期间以不同的速度翻转。在用我们的周转工具对这些数据进行分析时，我们已经确定了与年龄相关性骨骼肌萎缩发展相关的线粒体和肌原纤维蛋白的子集，这些蛋白的周转发生了变化。这项研究现已发表。 此外，我们还与西雅图华盛顿大学的Oscar Vivas博士建立了合作关系，以确定在小鼠衰老相关的神经退化过程中蛋白质周转是如何变化的，以及哪些变化可以通过防止大脑老化的干预措施来挽救。这项研究的小鼠代谢标签已经开始。 最后，我们已经为第一项临床研究编写了一份协议，全面评估人类在多个组织和年龄中的蛋白质周转。我们预期该局会在来年批准及展开这项研究。

We have made significant progress toward the first goal of developing of a software tool within the Skyline proteomics platform. We have worked with the Skyline core development team (Michael MacCoss and Brendan MacLean at the University of Washington in Seattle) to develop a software tool that is now available in the Skyline External Tool store. This manuscript has now been published in the Journal of Proteome Research. Toward our second objective, we have conducted the first mouse study utilizing this tool to determine which proteins are turned over at different rates during muscle atrophy in collaboration with Dr. Christopher Adams lab at the Mayo Clinic in Rochester, MN. In the analysis of this data with our turnover tool, we have identified a subset of mitochondrial and myofibrillar proteins with altered turnover that are associated with the development of age-related skeletal muscle atrophy. This study has now been published. We have additionally established a collaboration with Dr. Oscar Vivas at the University of Washington in Seattle to determine how protein turnover is altered during aging-related neurodegeneration in mice, and which alterations are rescued by interventions that are protective against brain aging. Metabolic labeling of mice for this study has begun. Finally we have written a protocol for the first clinical study that comprehensively assesses protein turnover in humans in multiple tissues and ages. We anticipate IRB approval and initiation of the study in the coming year.