Oklahoma Nathan Shock Center of Excellence in Basic Biology of Aging

ABSTRACT/SUMMARY – OVERALL Advances in understanding of molecular mechanisms of aging in the last decades, including the discovery of manipulations that delay aging and increase healthspan, led to the creation of a new field of study, geroscience. The translation of current knowledge of aging to interventions to prevent or treat age-associated dysfunction and disease, however, is limited. The Oklahoma Nathan Shock Center (NSC, `Center') focuses on geroscience, unique among NSCs. Geroscience is central to the goals and strengths of our host institutions: the University of Oklahoma Health Sciences (OUHSC), the Oklahoma Medical Research Foundation (OMRF), and the Oklahoma City VA Medical Center (VAHCS). The primary goal of the NSC is to serve as a national resource to enable sustained, accelerated progress in biology of aging and geroscience research, to help bring interventions to the clinic sooner. We will achieve our goal by (1) Offering investigators access to unique advanced technologies to enable transformative basic and translational research on aging/geroscience; (2) Providing intellectual and organizational leadership to the field; (3) Disseminating knowledge of aging biology and its association with human disease; (4) Providing intensive mentoring to early-stage investigators to become the next generation of leaders in aging/geroscience research; (5) Promoting access and opportunity for all investigators in all Center's activities, specially early-stage investigators; and (6) Disseminating knowledge of aging and geroscience to our local and national communities. We will regularly and objectively evaluate progress towards these goals. The aging/ geroscience research program in Oklahoma, nucleated by the NSC, has grown 450% since the Center's inception in 2015 and promoted growth of aging/geroscience research in the nation. The NSC has provided 554 services (285 this cycle), largely to external investigators, with 111 publications and 58 funded investigator-initiated grants in this funding cycle. Seven outstanding early-stage investigators (6 external) are currently in our Mentorship Program. Through the coordinated, cohesive activities of our Cores and the Center's interactions with local programs, other NSCs (U Washington, U Alabama, and JAX), and the NSC3, our proposed Center will continue to achieve a whole that is greater than its individual parts. Together with our administrative and research development cores, we will achieve our Center's goal through the (1) Multiplexing Protein Analysis Core, that provides data- independent acquisition mass spectrometry and metabolic labeling to measure protein steady-state levels and turnover rates; (2) Genomic Sciences Core, that maps the epigenome and measures mitochondrial heteroplasmy and copy number using next-generation or long-read nanopore sequencing; (3) Redox Biology Core, that measures redox status (including radical species), oxidative damage, and mitochondrial function (also in frozen tissues), and related metabolites; and (4) CRISPR Whole-Genome Screening Core, that uses CRISPR to knock out individual genes, one by one, in a high-throughput, rapid fashion, to identify those that mediate aging or age- associated disease phenotypes modeled in practically any human or mouse cell type, including primary cells.