Preclinical studies aimed at elucidating the mechanism of action or establishing the proof-of-concept of function promoting therapies (FPTs) in animal models are predicated critically upon the ability to measure the effects of FPTs on whole body and regional skeletal muscle mass and quality, muscle mechanics and performance, energetics, blood flow, and physical function. Based upon surveys of core users, and in consultation with OAIC's Advisory Board, the Executive Committee established a Small Animal Resource Core (SARC) in year 3 of OAIC's first cycle. Additional feedback from the SARC users led to the recognition that the physician scientists, especially geriatricians with limited experience with laboratory animals, needed substantial guidance in the selection of appropriate animal model, genetic model identification, outcome selection, experimental design and the execution of FPT studies. Accordingly, the consultative role of the SARC core was expanded and the core was re-named the Preclinical Discovery Core (PDC). In its initial brief funding cycle, the PDC supported 3 PES projects, 2 REC project, and 7 external projects. The studies utilizing the PDC infrastructure have resulted in 17 peer-reviewed publications, including several high- impact publications in leading journals including PNAS (2 papers), Cell Metabolism (1 paper), Blood (1 paper), Diabetes (1 paper), and Aging Cell (2 papers), and $8.42 million dollars in grant funding.
The specific aims of the PDC are to provide the infrastructure, consultative support, and standardized methods to assess whole body and regional skeletal muscle and fat mass, muscle performance and energetics, metabolic outcomes, and physical function in preclinical models of aging and illness. The PDC will develop novel non-invasive imaging methods to measure myofibrillar space, perfusion, energetics, and regeneration in preclinical models of FPT action. The PDC will implement rigorous quality control by personnel training and certification in standardized procedures for assessment of muscle performance and physical function, and by maintaining equipment calibration. The developmental project (DP3) will develop an innovative non-invasive method for quantitative assessment of myofibrillar space, muscle perfusion, energetics, and muscle oxygen uptake, using 7 Tesla magnetic resonance imaging and spectroscopy. The PDC has introduced several innovations, including: integration of new T1 and T2 sequences for improved precision of body composition assessment by NMR; coupling of core body thermogenics with energy expenditure assessment; integration of high sensitivity motor electronics to improve the precision and accuracy of ex-vivo strength measurements; and improving the precision of grip strength measurements. The highly specialized services and expertise offered by PDC is unique among OAICs, and central to the successful execution of several external and OAIC projects.
Resource Core III: Preclinical Discovery Core NARRATIVE The overall objective of the Preclinical Discovery Core (PDC) is to provide a focal point for interdisciplinary collaboration by Boston OAIC investigators in the application of existing and new tools to assess muscle impairments, metabolic alterations and functional decline with aging and illness, and to determine the efficacy to function promoting therapies in preclinical models. PDC institutes standardized, state-of-the-art methods to measure whole body and regional skeletal muscle mass, muscle performance, energetics, metabolic outcomes, and physical function in preclinical models of aging. In collaboration with experts in magnetic resonance imaging and spectroscopy, the PDC is developing an innovative, non-invasive method for the measurement for longitudinal measurements of myofibrillar space, muscle perfusion, and muscle regeneration in preclinical models of aging and illness.
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