A core tenet of the geroscience concept is that multiple human diseases arise from aging itself. Thus, the central theme of the San Antonio (SA) Claude D. Pepper Older Americans Independence Center (OAIC) is translational geroscience – moving research on the basic biology of aging from the laboratory bench to the clinic, with the overarching goal of promoting healthy aging and developing desperately needed treatments, mainly pharmacological, for aging-related diseases. This goal is achieved through the following Aims: 1) Expand the knowledge base in translational geroscience by catalyzing transformative research; 2) Create a cadre of multidisciplinary early-stage investigators with customized expertise in translational geroscience; 3) Serve as a resource and partner to investigators from other OAICs and institutions; and 4) Provide intellectual leadership, disseminate knowledge, and stimulate discussion on translational geroscience-related themes. The SA OAIC achieves these Aims through a Leadership and Administrative Core (LAC) that directs operations and sponsors several enrichment and dissemination activities; a Pilot and Exploratory Studies Core (PESC) that provides merit-based support for rigorously designed studies; a Research Education Component (REC) that expands a greatly needed cadre of uniquely qualified scientists cross-trained in aging biology and translational geroscience; a Pre-Clinical Research Core (RC1) which supports research in marmoset monkeys; a Clinical Research and Pharmacology Core (RC2) that delivers comprehensive trial support for recruitment/retention, assessments, pharmacology, and data management; and a Trial Design and Integrative Informatics Core (RC3) that provides comprehensive study design, biostatistics and informatics services. During the ~4 years since its funding, the SA OAIC supported 46 PIs, performing transformative translational geroscience-focused research in essentially all pillars/hallmarks of aging. For example, RC1 is conducting the only known lifespan and healthspan study on mTOR inhibitors in nonhuman primates. RC2 and RC3 carried out the first trial on rapamycin to examine immune and cognitive effects in healthy older adults and performed the first-in-man studies on senolytics. The OAIC supported 10 Scholars who are making transformative discoveries (e.g. first demonstration of cellular senescence as a key mediator of Alzheimer's pathology) and receiving highly competitive career development awards from the NIA/AFAR (Beeson, Irene Diamond) and the VA. The SA OAIC is built on a unique foundation provided by UTHSCSA's exceptional and tightly integrated resources: a Nathan Shock Center, a site of the Interventions Testing Program (ITP), a GRECC, a T32 Training Grant on Geroscience, and a robust Barshop Institute that unites aging research at UTHSCSA. We are the only OAIC with all of these synergistic components available. In addition, the SA OAIC receives unparalleled institutional commitment (~$600,000/year), including a new ~$100M 109,000 sq. ft. building – specific for the Barshop Institute – that will house the OAIC, Shock Center, and the ITP in a centrally located facility.
The SA OAIC catalyzes scientific discoveries, promotes education and mentorship, and partners with other scientists and the community at large to develop novel interventions to improve the health, quality of life, and independence of older Americans. The LAC monitors, stimulates, sustains, evaluates, and reports progress toward the SA OAIC's goal through the following Specific Aims: 1) Provide logistical support and promote operational cohesiveness to our OAIC; 2) Promote research protocol adherence and maintain regulatory compliance with university and governmental policies for the responsible conduct of OAIC-supported research; 3) Disseminate the scientific innovation accomplished by OAIC investigators, inside and outside our institution, regarding the latest knowledge on geroscience and promotion of healthy life extension; 4) Stimulate and facilitate interdisciplinary collaboration among OAIC investigators, cores, committees, and projects, to advance basic science in aging biology from the bench to the clinic; 5) Select and monitor pilot and exploratory studies and progress of Scholars aligned with the OAIC theme; 6) Monitor and evaluate OAIC progress, foster institutional collaborations, and leverage resources; 7) Provide programmatic and scientific guidance to training programs, pilot studies, and resource cores (RCs); and 8) Participate actively in the national OAIC network to help advance its mission of promoting independence in older Americans. The LAC coordinates annual reviews by an External Advisory Committee, an Institutional Advisory Committee, and a Research Education Component (REC) Advisory Committee. With RC2, the LAC supports a Community Advisory Committee (CAB). The LAC sponsors a weekly seminar on Geroscience, a monthly OAIC Executive Committee Meeting, an Annual Conference on Aging (a 3-day activity), two one-day symposia on aging per year, and bi-annual retreats where OAIC Scholars and pilot funding recipients present and discuss their work with UTHSCSA leadership and local experts. These activities enable a rich scientific and academic environment that further catalyzes transformative discoveries in translational geroscience. The LAC implements an online research service tracking and management system developed by RC3 (PROS) for effective monitoring and evaluation of activities and key performance indicators, and efficient preparation of reports. The LAC also provides an electronic management and communications platform that enhances cohesion within the SA OAIC. The LAC promotes application of advanced managerial concepts (e.g. Lean Six-Sigma) to streamline OAIC operations and foster coordination within RCs. Collectively, LAC initiatives and activities have been extremely successful in optimizing performance of the services that support science and advance the overall goals of our OAIC.
The overarching goal of RC2 is to offer comprehensive, centralized, clinical trial support for study design, regulatory compliance, recruitment, retention, assessment, procedures, pharmacology, and data management. During the initial award cycle, RC2 quadrupled (to 20) its number of trials, the majority of which were phase 1 trials to evaluate safety and tolerability of compounds in healthy older adults and phase 2, proof-of-concept studies to obtain preliminary data on efficacy and functional parameters (e.g. healthspan) in patients with age- related disease. Major accomplishments made by OAIC members with RC2 support include: the first study of rapamycin in healthy older adults; the first senolytics trial in humans; and launching of an NIH-funded long-term trial of metformin for frailty prevention. RC2 played a key role in the career development of OAIC Scholars who received highly prestigious grants, including a K76 Beeson Award and a VA Career Development Award-2. RC2 has built a robust program to insure that good clinical practice (GCP) is followed in clinical studies. Our programs include: subject recruitment and retention, a subject registry and repository, a data safety monitoring board (DSMB), a Geriatrics Practice Based Research Network (PBRN), and a community advisory board. RC2 provides critical clinical pharmacology services to support biospecimen (plasma, CSF, urine, muscle, adipose) collection, or to measure levels of drugs (e.g. metformin, senolytics) or ensure safe administration of local anesthetics to participants receiving biopsies. RC2 contributed to the overall OAIC program mission by closely collaborating with other geroscience programs, including multi-center, phase 2 studies on senolytics and stem cell activators (e.g. oxytocin), and multi-center trials such as the Molecular Transducers of Physical Activity Consortium (MoTrPAC), ASPREE-XT, and DPPOS. RC2 achieves its mission through the following Aims: 1) Provide expertise and advice for investigators to plan and design innovative clinical studies to rigorously test interventions to improve healthspan; 2) Enhance the SA OAIC support infrastructure to ensure successful subject recruitment and safe and ethical conduct of all OAIC-supported clinical studies; 3) Catalyze translational human studies and trials through provision of comprehensive core services; 4) Provide analytical and clinical pharmacology expertise supporting drug pharmacokinetic, and pharmacodynamic analyses as well as toxicity and safety assessment; 5) Disseminate to the lay public and scientific community the latest research on geroscience-related health promotion and the importance/relevance of translational geroscience research; and 6) Support training in translational geroscience for early-stage faculty and those new to clinical research. In the first year of the next award cycle, RC2 plans to support 3 pilot, 3 Scholar, and 10 external projects. Additionally, RC2 will begin 3 developmental projects (DPs) with highly innovative features: DP1 entitled “Human-marmoset comparative assessment of the role of mTOR in cardiac aging”, DP2 “Comparative lipidomics of aging”, and DP3 “Development of senescence biomarkers for clinical trials.”
