Leadership / Administrative Core (LAC): Project Summary This Johns Hopkins University (JHU) Older Americans Independence Center (OAIC) Leadership and Administrative Core (LAC) was designed to provide the scientific leadership, organization and infrastructure necessary to lead and oversee the frailty-focused activities of this OAIC. The overall goal of the LAC is to ensure the ongoing success of this OAIC in stimulating and sustaining the next generation of frailty-related science and the next generation of frailty-focused investigators. The aims of this LAC are to: 1) provide the interdisciplinary intellectual leadership needed to stimulate and sustain the development of innovative frailty- focused research, facilitate translation between basic and clinical research on frailty, develop innovative intervention and prevention strategies from these biological and clinical discoveries, and ensure effective, high impact utilization of each of the cores of the OAIC; 2) identify and attract the next generation of frailty- focused research leaders at JHU and facilitate their training, career development and access to resources to promote their emergence as independent, interdisciplinary investigators in this field; 3) lead, administer, and oversee core functions to assure productivity, cost effectiveness, integration, and quality of all aspects of this OAIC program, and well steward OAIC resources; 4) prepare reports or non-competing renewal applications, annually, and administrative documents as needed, including data safety monitoring documentation; 5) organize and conduct scientific sessions to propel the frailty-focused science and career development of participants, including OAIC retreats, research in progress meetings, and research planning meetings; 6) maximize JHU OAIC scholarly visibility locally and nationally via local programming and participation in the OAIC network, the annual OAIC scientific meeting, annual scientific meetings of organizations focused on aging or frailty, and through a new Information Dissemination Core; and 7) organize independent panels for review of pilot, development project and junior faculty applications and organize review of progress towards OAIC goals, conducted annually by an External Advisory Board. This Core will set goals with all other cores and ensure that goals are met. It will lead visioning discussions among the multidisciplinary Leadership Council as to scientific direction and clinical relevance; provide institutional leadership in identifying the investigators and mechanisms to accomplish the Center's scientific goals; and provide leadership and organization to ensure the successful development and implementation of the infrastructure and new methods needed to support investigators in furthering research on frailty and its translation to increase the independence of older adults.
This administrative supplement to the the Johns Hopkins Older Americans Independence Center (OAIC) is designed to capitalize on the Center's expertise on intersecting biological pathways that drive early onset of physical frailty in a subset of individuals living with HIV through the study of mitochondrial decline as articulated in this proposal. Among people with HIV (PWH), frailty predicts mortality, comorbidities, and hospitalization, and is an important indicator of quality of life. The underlying mechanisms for frailty development are likely multifaceted, due in part to features of biological aging such as mitochondrial decline and chronic inflammation. A major driver of the aging process in PWH is mitochondrial damage, resulting from chronic HIV infection, chronic inflammation, and the effects of some antiretroviral therapies. However, the role of changes in mitochondrial function in the etiology of frailty among PWH remains unclear. Furthermore, each immune cell type may develop different metabolic adaptations in response to stress. The interplay between mitochondrial function and immune activation and senescence in the etiology of frailty development remains unclear. We propose to evaluate the association of immune cell type- specific mitochondrial function measurements, including mitochondrial content, membrane potential, and superoxide, with HIV infection and frailty by leveraging longitudinal data, specimens, and infrastructure from two established HIV cohorts: 1) the AIDS Linked to the IntraVenous Experience cohort; and 2) the Multicenter AIDS Cohort Study. These cohorts uniquely include PWH and comparable HIV uninfected adults. We propose the following aims to accomplish these goals: (1) to characterize immune cell activation and senescence and cell type- specific mitochondrial function, stratified by HIV infection status; and (2) to assess the association between cell type-specific mitochondrial function and frailty during longitudinal follow-up among people with and without HIV. We will apply a novel machine learning approach to characterize the complex and high-dimensional biomarker data in immune aging and mitochondrial function to achieve these aims. With expertise and resources from the OAIC, we will provide data on the longitudinal change of cell type-specific mitochondrial function profiles before and after frailty development, which will allow us to observe variations in mitochondrial function among people with and without HIV. These aims will provide new understanding of the interplay between HIV infection, immune aging, and mitochondrial function in the etiology of frailty.
