Mark Miller - US grants

Project Summary. The Administrative Core forms the nucleus of the COBRE Phase II Center for Neuroplasticity at the University of Puerto Rico. As such, it will support the three-fold objectives of the COBRE Center: 1) Develop and maintain a nationally competitive biomedical research program focused on the theme of Neuroplasticity; 2) Facilitate the developmental trajectory of junior investigators toward their transition to independent research careers; 3) Support the COBRE NeuroImaging and Electrophysiology Facility (NIEF). The Administrative Core incorporates all programmatic facets of this initiative, including Faculty Career Development Activities (Laboratory Management, Grant Writing, Manuscript Preparation) and Neuroscience Research Infrastructure Enhancement programs (Seminar Series, Neuroscientist-in-Residence, Annual Puerto Rico Neuroscience Conference, Outreach Activities, and Academic Partnerships). The Administrative Core is composed of a team of individuals with proven track records and experience in the operation and management of large multi-faceted research and training programs. Oversight of the Core is the responsibility of the COBRE Associate Director, Dr. Mark Miller. Miller serves as liaison between the program and its Evaluation Module and he coordinates communication with NIGMS officials. The Administrative Support Office will continue to be staffed by a highly experienced and dedicated team including: Ms. Bethzaida Birriel, Grants Administrator; Ms. Brenda Caban, Accountant; and Ms. Sandra Felix, Purchasing Agent. All fiscal matters will be managed at the Institute of Neurobiology, a free- standing unit under the Deanship of Academic Affairs of the University of Puerto Rico Medical Sciences Campus. Institute personnel will handle most aspects of the post-award administration of funds, including hiring of technicians, postdocs, and students. Finally the Administrative Core will coordinate all program appraisal and assessment, including the participation of an independent external evaluation group from Cooperativa de Servicios de Evaluación e Investigación (CoopSEI). The Administrative Core team will organize the Annual COBRE Retreat and Assessment Activity that will enable all stakeholders to meet, exchange ideas, report progress, and plan future strategies. This meeting will serve as the principal forum for developing and disseminating data required for formative and summative evaluation of all COBRE Center research objectives and programmatic initiatives.

PROJECT SUMMARY In general, men and women experience differing degrees of age-related decreases in physical function, with women having a greater prevalence of functional limitations and disability. A key predictor of this decrease in functional capacity is the reduction in leg muscle maximal power (product of force and velocity), which can be improved with exercise training. However, the development of exercise interventions to optimally improve skeletal muscle function in older adults has been difficult, in part because we now know that men and women respond differently to the same exercise training stimulus. In fact, the fundamental mechanisms by which habitual exercise improves physical function in older adults are still not well understood. The proposed studies, which build upon our recent work, are designed to address these knowledge gaps by examining the molecular and cellular mechanisms underlying the response to two distinct exercise training paradigms, and determining how these responses differ between older men and women. We hypothesize that molecular, cellular and whole muscle contractile performance will be most improved in men by traditional low-velocity, high-load resistance training, and in women by high-velocity, low-load power training. Moreover, sex-specific structural responses in myofilament remodeling, protein expression and post- translational modifications will explain these sex-specific performance adaptations to each modality. To test our hypotheses, data will be gathered from 50 healthy, sedentary older men and women (65-75 years) prior to and following a 16-week unilateral exercise training program in which one leg undergoes resistance training and the other power training. The Specific Aims of this project are to identify the sex-specific effects of low-velocity resistance training versus high-velocity power training on: Aim 1) skeletal muscle function at the molecular, cellular and whole muscle levels, and Aim 2) protein expression and modification as well as size at the molecular and cellular levels. Our within subject, unilateral intervention design provides a powerful model to minimize the effects of between-subject variability, and our translational approach will take advantage of our unique expertise with state-of-the-art measures from the molecular to whole body levels. Our results will challenge conventional wisdom by determining the sex-specific responses in intrinsic skeletal muscle adaptations to different exercise training programs. We will advance scientific knowledge by providing critically- needed information regarding the specific molecular and cellular determinants that support exercise-induced improvements in muscle performance. This knowledge will have a significant positive impact on the clinical care of older adults by providing novel insight about optimal exercise interventions to improve skeletal muscle function in each sex, and by identifying potential new therapeutic targets for pharmaceutical interventions. Thus, this project is highly relevant to the mission and vision of NIA to support biological research to mitigate conditions associated with aging that may limit health and independence in older adults.