Leadership and Administrative Core (LAC)
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PROJECT SUMMARY – LEADERSHIP and ADMINISTRATIVE CORE (LAC) The overall goal of this newly proposed Los Angeles Claude D. Pepper Older Americans Independence Center (LA OAIC) between Cedars-Sinai Medical Center (CSMC), the University of California Los Angeles (UCLA), and the University of Southern California (USC) is to extend healthspan of older adults by advancing translational geroscience. We will accomplish this goal by providing knowledge, resources, and novel methodologies to emerging geroscientists – both early-stage investigators and established investigators new to the field. The LA OAIC draws upon multiple strengths of our shared scientific environment, including several collaborating NIA- and VA-funded programs such as two Clinical and Translational Science Institutes, two Resource Centers for Minority Aging Research, a Geriatric Research Education & Clinical Center, an Alzheimer’s Disease Research Center, and several education and research training programs in geroscience, gerontology, and geriatric medicine. The Leadership and Administrative Core (LAC) fosters the integration of basic, translational, and clinical research in aging and geriatrics to catalyze scientific discoveries in translational geroscience, promote education and mentorship, and partner with other scientists and the community to develop novel interventions to improve the health, quality of life, and independence of older adults. The LAC monitors, stimulates, sustains, evaluates, and reports progress toward our OAIC’s goal. The Specific Aims of the LAC are to: 1) Provide direction and logistical support to operate the Center, manage resources, and promote cohesiveness of the program. 2) Disseminate innovations in translational geroscience accomplished by LA OAIC investigators, locally, nationally, and internationally. 3) Stimulate and facilitate interdisciplinary collaboration among LA OAIC investigators and its cores, boards, committees, and projects, as well as with external researchers. 4) Provide programmatic support to the Pilot and Exploratory Studies Core (PESC), Research Education Core (REC), and Resource Cores (RCs) to select and promote projects and Scholars whose research is aligned with the LA OAIC theme. 5) Monitor and evaluate LA OAIC progress, foster institutional collaborations, and leverage resources through the Institutional Advisory Board (IAB). 6) Work with the External Advisory Board (EAB) to guide training programs, pilot studies, and RCs. 7) Serve as the point of contact for the NIA and the OAIC Coordinating Center to actively participate in the national OAIC network.
PROJECT SUMMARY – OVERALL We propose the creation of the Los Angeles Claude D. Pepper Older Americans Independence Center (LA OAIC), the joint effort of three pre-eminent institutions, Cedars-Sinai Medical Center (CSMC), University of California Los Angeles (UCLA), and University of Southern California (USC). The overarching objective of the LA OAIC is to extend human healthspan by accelerating and expanding translational geroscience. The Specific Aims of the LA OAIC are to: (1) Develop advanced gerotherapeutics for extension of human healthspan; (2) Expand the scope of clinical trials in translational geroscience; (3) Increase the research workforce in translational geroscience; and (4) Provide leadership, enhance implementation, and promote dissemination of knowledge about geroscience. The LA OAIC will achieve these Aims through the following cores: (1) A Leadership and Administrative Core (LAC) that will direct operations and sponsor enrichment and dissemination activities; (2) A Pilot and Exploratory Studies Core (PESC) that will provide scientific guidance and merit-based support for rigorously designed geroscience-guided studies and offer “mini-sabbaticals” for faculty to visit other laboratories; (3) A Research Education Component (REC) that will build a cadre of uniquely qualified scientists cross-trained in aging biology and translational geroscience; (4) An Advanced Gerotherapeutics Core (Resource Core [RC]1) that will provide expertise and infrastructure for discovery, development, and translation of novel interventions with gerotherapeutic potential; (5) A Clinical Research Core (RC2) that will provide direction and clinical research infrastructure for the evaluation of gerotherapeutics and gerodiagnostics in humans; and (6) A Data Science Core (RC3) that will provide biostatistical and bioinformatics expertise for experimental design, data analysis, and integration of multimodal geroscience data using AI and machine learning. The proposed LA OAIC is built on a robust foundation provided by the expertise of its leadership and members, many of whom have been pioneers in aging biology, geriatrics, and translational geroscience; exceptional research environments and resources in geroscience; and our location in the second largest metropolis in the U.S. with broad representation. LA OAIC will function as a vibrant hub for geroscience research and education. We anticipate that by the end of the project period the LA OAIC would have catalyzed the discovery and clinical translation of novel molecular targets and interventions with gerotherapeutic potential and the identification of novel gerodiagnostics/biomarkers to predict and monitor response and direct personalized interventions. Furthermore, the LA OAIC will prepare a cadre of outstanding scientists with the necessary skill sets for successful careers in translational geroscience.
PROJECT SUMMARY – RESOURCE CORE 2 (RC2), CLINICAL RESEARCH CORE The Clinical Research Core (RC2) will play a central role in the Los Angeles Claude D. Pepper Older Americans Independence Center (LA OAIC) by facilitating the translation of discoveries in the biology of aging from the laboratory bench to the clinical arena. RC2 is a comprehensive clinical trials program that will provide the knowledge, skills, and technical support to conduct global evaluations of rigorously-designed gerotherapeutic clinical interventions to extend healthspan and treat aging-induced diseases. RC2 will expand the scope of translational geroscience by promoting clinical trials across the clinical development spectrum, from proof-of-concept to multi-center clinical trials. It will provide centralized, clinical trial support for study design, regulatory requirements, recruitment and retention, assessments, procedures, and data management. The Specific Aims of RC2 are to: Aim 1) Provide expertise to investigators for the planning of innovative studies to study human aging biology and rigorously evaluate interventions for healthspan extension; Aim 2) Provide clinical research infrastructure to ensure successful participant recruitment and safe and ethical conduct of all LA OAIC-supported clinical studies; Aim 3) Promote the conduct of geroscience-guided multicenter Phase 2 and Phase 3 clinical trials; and Aim 4) Provide translational geroscience training to early-stage scientists and those new to clinical research. To facilitate studies of the impact of potential gerotherapeutics on healthspan-related parameters, RC2 will assist investigators by performing comprehensive functional assessments. RC2 will collect biospecimens (blood, muscle, adipose, skin, urine, cerebrospinal fluid, microbiome) for studies of cellular aging, target engagement, measurements of drug/compound levels, and biomarkers. Also, RC2 will leverage and augment a recently created longitudinal cohort study of participants (Los Angeles Cohort on Aging [LACA]) that will serve as a resource of biological, clinical, and phenotypic data for translational geroscience studies in humans. In the first year of the next award period, RC2 plans to support 4 pilot (PES), 3 Scholar (REC) and 12 external projects (EPs). Additionally, RC2 will support 2 highly innovative developmental projects (DPs). • DP-3 will leverage a novel NIA-funded trial on metformin vs. placebo for frailty prevention in older adults to test and compare the performance of several omic-based biological clocks and determine their potential to predict changes in healthspan phenotypes and clinically-relevant, actionable outcomes. • DP-4 will use cells from the LACA cohort to develop subject-cell specific and human induced pluripotent stem cell-based models for drug screening and target identification for gerotherapeutic development. We anticipate that by the end of the funding period, RC2, in conjunction with the LA OAIC and external colleagues, will have identified novel interventions with potential to extend healthy longevity in people.
SUMMARY – PILOT / EXPLORATORY STUDIES CORE The Pilot / Exploratory Studies Core (PESC) advances the LA OAIC’s central mission of accelerating the field of translational geroscience through the solicitation, selection, and support of innovative research studies that have strong potential to contribute to discoveries integral for advancing and extending human healthspan. The PESC, in close collaboration with the Research Education Component, will support and foster the scientific development of early career investigators (ESI) and new investigators, including basic, translational, and clinical scientists . The PESC will employ an evidence-based approach that encompasses formal mentorship, education, frequent opportunities for collegial, collaborative interactions, and pilot award funding. Recognizing the critical role of well-designed pilot and exploratory studies to initiate new innovations in the field, the PESC will fund 5 pilot awards annually. The PESC will prioritize rigorously designed studies that evaluate the feasibility of new research methodologies, as well as promising pharmacological, non-pharmacological, cell-based and behavioral interventions that target fundamental biological aging processes and/or age-related conditions. The PESC will support projects spanning from basic to clinical sciences with strong encouragement of proposals bridging translational research stages. The PESC will also solicit applications evaluating the feasibility of integrating research findings into healthcare implementation strategies. In addition to the pilot study awards, the PESC will fund 6 Stimulating Advanced Geroscience Experiences (SAGE) Mini-Sabbaticals annually, which provide applicants with the unique opportunity of immersive research experience in a faculty member’s laboratory or Core Facility at any LA OAIC affiliated institution. This award mechanism is designed to allow investigators to develop new methodological approaches and/or skills that can be disseminated to the applicant’s home institution, delivering a sizable return on investment. The PESC will establish a Translational Research Activities to Completion Keystone (TRACK) team to oversee funded projects from inception to completion. The TRACK team will engage in collaborative problem-solving to overcome unanticipated obstacles, aid in strategic decision making necessary for project completion, and support the awardees in delineating and achieving next steps to advance their research. To assess the long-term impact of LA OAIC support, the PESC will monitor abstracts, publications, scientific presentations, community presentations, awards and promotions, and funding resulting from the LA OAIC activities. The LA OAIC will amplify and promote the continued success of PESC award recipients, integrating them into the overall network of scientists and institutions advancing translational geroscience.
