DESCRIPTION (provided by applicant): The specific aims of the UTMB Claude Pepper Older Americans Independence Center (OAIC) are to: 1) provide core support to funded translational research by UTMB investigators on muscle function and functional recovery in older adults; 2) Stimulate the growth of additional interdisciplinary translational research projects to improve muscle function and functional recovery in older adults by: a) funding pilot project research to generate preliminary data in promising new areas of investigation and b) funding developmental projects to develop innovative technologies; 3) Train future leaders in research in the mechanisms, prevention and treatment of muscle dysfunction and disability in older adults; 4) Recruit established investigators with expertise relevant to muscle function and functional recovery in older adults into interdisciplinary translational research related to the OAIC focusi and 5) Foster collaborations between UTMB investigators and investigators at other OAIC and other institutions on studies of muscle function and functional recovery in older adults. The theme for the next cycle of our OAIC is: Translating Biological Mechanisms of Muscle Growth and Loss to Improve Function and Recovery in Older Adults. Our focus is on translating basic discoveries on the mechanisms of muscle loss and re-growth with aging to clinical practice to promote functional recovery and prevent disability in older adults. Observational sutidies will provide crucial information for selecting appropriate in-hospital, post-discharge, and long-term outcomes for inclusion in clinical trials of geriatric patient populations. Our general hypothesis is that aging induces mild but significant changes in muscle biology and function that progressively lead to muscle loss and predispose to potentially catastrophic declines in muscle mass and function during bouts of acute illness. We also hypothesize that anabolic interventions involving exercise/rehabilitation, amino acid/protein supplementation and hormonal or other pharmacological treatment can prevent the age- and disease-induced muscle loss and reduce the risk of
Studies in animal models of aging have suggested that there is a reduced potenfial for adipocyte maturation during the aging process. This could result in a defective capacity for storage of excess energy during overfeeding, and adipose fissue dysfunction. The resulfing abnormalifies in systemic lipid and glucose metabolism (including insulin resistance) are known contributors to risk for cardiovascular disease, a major cause of disability in the elderiy. We have recently found that when compared to Caucasian controls matched for age, gender and body composifion, young lean Asian Indians have much larger adipocytes and lower indices of new adipocyte formafion, which are associated with a significant reducfion in insulin sensifivity. Our hypothesis is that in older adults a reduced ability to form new adipocytes (whether through lack of proliferation or maturation arrest), in combinafion with adipocyte lepfin resistance, induces adipose fissue dysfuncfion and insulin resistance. The specific aims that we will test are the following: 1. To determine in subcutaneous abdominal fat if there are age-related differences in the size of the adipocytes, expression of genes involved in new adipocyte formafion (such as pref-1, INSIG-1, PPARgamma), and leptin sensifivity (lepfin receptor, S0CS3, PTP1B, AMPK phosphorylafion). 2. To determine if there are age-related differences in adipose tissue triglycerides kinetics (triglyceride synthesis, net lipolysis, glyceroneogenesis) and adipocyte proliferafion using long-term ^H20 labeling. We will study non-diabefic young and older volunteers matched for gender, body fat content, and fat distribution. The results of this study will provide the necessary preliminary information to apply for larger grants to evaluate the role of adipose fissue dysfuncfion in the development of metabolic abnormalifies associated with aging.
The Muscle Biology Resource Core (MB-RC2) is the result of the merger of our current Metabolism Research Core and Proteomics/Genomics Core in response to the shift in focus of our OAIC. The merger will simplify access to the analytical resources, improve coordination of sample flow, coordinate multiple analyses of individual samples, reduce analytical time and costs, and increase efficiency and quality control.
The overarching goal of the UTMB OAIC is to promote innovative interdisciplinary research to improve recovery and maintain muscle function in older adults by translating biological mechanisms of muscle growth and loss into improved function and recovery in older adults. To achieve our goal the LAC will coordinate and integrate the activities of all OAIC cores and maintain a high quality and highly productive research and training program by carrying out the specific aims of the core.
