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

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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. A manuscript describing this work has been accepted 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 manuscript is in preparation. 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.