CORE--PRE-CLINICAL RESEARCH CORE

Wake Forest University Health Sciences, Winston-Salem NC

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Pre-clinical Research Core (RC-B) is an important resource of the OAIC providing the infrastructure and investigators for conducting both basic science and translational research related to the goals of independently funded studies, research development projects and pilot studies. The Core will test hypotheses on the etiology of muscle loss with age (sarcopenia), establish relationships between growth hormone/IGF-1, their signaling pathways, cytokine expression, physical performance and sarcopenia and assess the mechanisms of interventions designed to prevent disability in animal models. The Core has highly experienced investigators and the infrastructure to support the implementation of these added measures and support the development of the OAIC pilot projects. In the first year of funding, the Core builds on two currently funded NIA applications related to growth hormone (GH) and IGF-1 (Dr. William Sonntag) and alterations in excitation-contraction coupling in aged animals (Dr. Osvaldo Delbono) and has one research development project and one pilot. A rich environment is present for developing skills in basic sciences and translational research studies for junior investigators. The Pre-clinical Research Core projects will have direct applicability to other projects and Research Cores within the OAIC including the Body. Composition, the Genomics and Biomarkers and the Clinical Research Cores. Research Hypotheses: Age-related decreases in growth hormone and IGF-1 result in altered body composition, a decline in physical performance and increased cytokine expression in plasma and skeletal muscle. Cytokines impair IGF-1 signaling which results in excitation-contraction uncoupling in slow twitch muscle from aging rodents. Research objectives 1. To determine the effects of growth hormone and IGF-1 deficiency on body composition, physical performance and cytokine expression in plasma and skeletal muscle, type 1 and 2 fiber density and excitation-contraction coupling in slow twitch muscle. 2. Assess the effects of chronic TNFe inhibition on IGF-1 and IGFBPs, physical performance and body composition in type I slow twitch muscle fiber excitation contraction coupling in single fibers and whole skeletal muscle. 3. Determine the effects of ACE inhibitors on body composition, physical performance, cytokine expression and excitation contraction coupling in type 1 slow twitch muscle (whole muscle). Service and Infrastructure Objectives: To provide the investigators, infrastructure, environment and services necessary to support the OAIC research and educational objectives.