The Colorado Specialized Center of Research Excellence on Sex Differences (CO-SCORE) is thematically focused on Bioenergetic and Metabolic Consequences of the Loss of Gonadal Function. The overarching scientific objective of the CO-SCORE is to advance knowledge of the impact of gonadal aging on the regulation of bioenergetics, abdominal adiposity, and metabolism by conducting mechanistically-driven research across the basic-to-clinical translational spectrum. The scientific premise is that gonadal failure mediates biological changes that increase risk for chronic disease. The most well-studied example of this is the accelerated decline in bone mineral density at menopause and the associated osteoporosis risk. However, the extent to which gonadal failure increases risk for chronic diseases other than osteoporosis is poorly understood. This is a particularly important knowledge gap in women’s health, because gonadal failure is inevitable in women in mid-life, but rare in men until much later in life. The overarching educational objective is to engage new investigators in research aligned with the thematic focus of the CO-SCORE. The CO-SCORE will promote mentored career development and provide training on how to conduct research that appropriately addresses sex as a biological variable (SABV). These central objectives will be accomplished through the following Aims: 1) The three CO-SCORE Research Projects (basic, preclinical, and clinical) will advance cutting-edge, paradigm-challenging translational research on novel mechanisms postulated to contribute to the increased abdominal adiposity and associated metabolic dysfunction that occur in the estrogen-deficient state;; 2) The Career Enhancement Core (CEC) will provide a rich training environment to attract and support outstanding junior investigators with research interests related to the thematic focus of the CO-SCORE. SCORE Scholars and Pilot Awardees will be selected through a competitive process and participate in a comprehensive career development program;; 3) The Leadership Administrative Core (LAC) will provide infrastructural support for the Research Projects, CO-SCORE Pilot Projects, and the CEC, including biostatistics, data management, financial oversight, and administrative support. An evaluation specialist will use innovative strategies for assessing whether the research, trainees, mentors, and the CO-SCORE as a whole are achieving a high level of impact and reach;; and 4) The CO-SCORE will partner with other Centers and Programs at CU-AMC to elevate the visibility and multi-disciplinary reach of women’s health research and the importance of investigating SABV. Activities will target both scientific and lay communities at local, regional, and national levels. Achieving these Aims will position the CO-SCORE as a national leader in our targeted areas of women’s health research, and the CEC as a model program for training junior investigators...