Project Summary/Abstract (HIV and Aging Scientific Working Group) The long-term objectives of the Miami-CFAR HIV and Aging Scientific Working Group (HA-SWG) are to promote innovative and emerging areas of research in HIV and aging through multidisciplinary collaborations. Since its inception in February 2019, the HA-SWG is actively involved in research on mechanisms that address the specific challenges that significantly impact our HIV-infected aging population in South Florida and beyond. Our studies include evaluation of HIV-related comorbidities and immune dysfunction and their influence on frailty and cognitive decline. The overall theme of multi-morbidity research serves to broaden the potential and scope of our SWG. In this application, we are presenting a significantly modified SWG that was developed with a focus on knowledge-based activities through the creation of working groups. These groups will study specific research areas utilizing innovative approaches. The topic of metabolic regulation of the immune system in aging is under- investigated and how HIV infection interacts with age-related metabolic reprogramming of immune cells and its implications on the earlier onset of immune dysfunction and comorbidities demands further investigation. Our current approach to understand the physical and cognitive frailty in aging persons living with HIV (PWH) has translational relevance. The HA-SWG will further expand the scope of research in this area by investigating the role of the gut-brain axis and liver-brain axis in the processes of neuroinflammation, accelerated neurocognitive decline and cognitive frailty in aging PWH. Here we propose two specific aims of the HA-SWG. First, to develop and promote innovative cross-disciplinary and collaborative translational research in the areas of immunology, metabolic regulation, neuroinflammation, frailty and cardiovascular/liver co-morbidities. Second, we will develop educational and mentoring activities within the University of Miami (UM) scientific community while enhancing the research goals specified in Aim 1. By achieving these aims, the HA-SWG endeavors to create a platform for interdisciplinary research at UM by bridging the clinical challenges of frailty, cognitive decline and comorbidities. These efforts will also support basic science research studying the mechanisms underlying metabolic regulation of immunity in HIV and Aging. The HA-SWG is also committed to create a resource-rich infrastructure to support cross-disciplinary proposals related to HIV and aging, support Early Stage Investigators and researchers new to the field of HIV research. To achieve our goals, the HA-SWG is uniquely positioned to leverage clinical and basic research resources and expertise available to the Miami-CFAR and infrastructure available at UM through the McKnight Brain Institute, Center on Neurocognitive Science and Aging, Comprehensive Center on Brain Health, Clinical and Translational Science Institute, Diabe...