The PESC is co-directed by Robert Clark, MD and Randy Strong, PhD. The major objective of this core is to promote the overarching goals of the San Antonio OAIC to: 1) Expand the translational geroscience knowledge base, 2) Create a cadre of early-stage geroscience investigators, 3) Serve as a resource to other OAICs, and 4) Disseminate translational geroscience knowledge. The OAIC pursues these objectives by developing and validating interventions to enhance healthy aging and mitigate the progression of aging-associated processes and diseases. The PESC plays a key role in the San Antonio OAIC’s central theme of translational geroscience by supporting projects that move research on the basic biology of aging from the laboratory bench to the bedside, to extend healthy life expectancy. The PESC provides merit-based support for rigorously designed pilot studies that test efficacy and side effect profiles of promising pharmacologic and non-pharmacologic cell-based (e.g., stem cells, gene therapy) and behavioral interventions. Importantly, PESC supports both pre-clinical studies in marmoset models and early-stage clinical studies.
What types of studies will the PESC fund?
The PESC will support both preclinical studies in marmosets and early human trials, many focused on pharmacologic repurposing of compounds in clinical use for other indications. We will also consider new molecular entities, stem cells, gene therapy, behavioral modalities, and other novel approaches to improving health and functioning of older people, based upon emerging clinical or basic science research. Functional assessments will be included as appropriate and feasible – e.g., frailty, resilience. As a priority, the PESC will explicitly encourage high-risk projects with potential for high rewards.
How do the Pilot / Exploratory Studies interact with other OAIC cores?
PESC-supported studies must involve at least one other OAIC Resource Core. Similarly, the PESC will synergize with the Research Education Component (REC) by placing a high priority on meritorious proposals from OAIC Scholars and other young investigators studying aging-related interventions. PESC interacts extensively with the Leadership and Administrative Core for proposal evaluation, selecting projects for funding, oversight of funded projects, and working with pilot PIs to publish their findings, design follow-up studies, and develop grant proposals based on pilot data.
The PESC plays a central role in supporting the early-stage, potentially ground-breaking research in translational geroscience enabled by the San Antonio OAIC. We seek projects that: 1) are first-of-type conducted in marmosets or humans, 2) bring established investigators newly into translational aging research, and 3) help launch careers of the OAIC REC Scholars. Outcomes include peer-reviewed publications, presentations at national meetings, formation of new collaborative teams, academic advancement of team members, and securing independent competitive funding. Innovative features include our SNPRC partnership for marmoset studies, explicit encouragement of high-risk projects, a rapid response pilot mechanism, online application and review platform, mentoring and team science approaches, and close linkages with the Biggs Institute for Alzheimer’s and Neurodegenerative Diseases and the Parkinson’s Disease Center of Excellence.
Pilot Study Announcements and Applications
Annually, the PESC solicits letters of intent (LOIs), which are screened by the PESC Co-Leaders for programmatic and scientific consistency with the overall goals of the OAIC and resource availability (e.g., marmosets or patient populations). Those selected for further consideration are invited to prepare a full application.
The PESC supports up to five full projects, each with an OAIC budget of up to $50K/year (one being a shared marmoset project with the Southwest National Primate Research Center [SNPRC]). The PESC also considers Rapid Response proposals (up to $10K; decisions within 2 weeks of application) for small projects with clearly defined goals. Awarded funds are based on submitted budgets and reviewer input, with final decisions made by the OAIC EC. Duration of support will be 1-2 years; funding for Year 2 will require achievement of first-year milestones
Outcomes and Accomplishments
To date, the PESC has served 26 PIs through support for 19 regular pilots, 5 rapid response pilots, and 2 SNPRC collaborative projects. PESC-supported investigators have published a total of 83 papers, obtained 30 grants, and submitted an additional 16 pending grant proposals.
Current Pilot Studies (PES) include:
Differential effect of glucose regulating drugs on the onset and progression of frailty: healthcare analytics meets aging research.
Investigator: Tiffany Cortes, MD
Department of Medicine, UT Health San Antonio, San Antonio, Texas
Development of marmoset age-dependent iPSC line resources to determine single cell transcriptome and regulome atlas.
Investigator: Marcel Daadi, PhD
Disease Intervention and Prevention, Texas Biomedical Research Institute, San Antonio, Texas
Direct measurement of high‐energy phosphate compounds in breast cancer survivors in response to exercise ± creatine supplementation.
Investigator: Darpan Patel, PhD
School of Nursing, UT Health San Antonio, San Antonio, Texas
Mechanisms to Reduce Mental and Physical Fatigue Following Diet and Exercise Training in Older Adults.
Investigator: Monica Serra, PhD
Department of Medicine, UT Health San Antonio, San Antonio, Texas
Completed Pilot Studies include:
Establishing the effect of aging on hepatic steatosis and associated cardiovascular health in the marmoset towards development of new models.
Investigator: Amrita Kamat, PhD
Department of Medicine, UT Health San Antonio, San Antonio, Texas. 2021.
Evaluating the extent of transposable element activation in brain and fluid from patients with Alzheimer’s diseases.
Investigator: Bess Frost, PhD
Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, Texas. 2019.
Effect of SGLT2 inhibition on aging-related biomarkers in older obese adults with pre-diabetes.
Investigator: Carolina Solis-Herrera, MD
Department of Medicine, UT Health San Antonio, San Antonio, Texas. 2019.
NAD Modulation to Improve Cognition in Mild Cognitive Impairment (MCI).
Investigators: Becky Powers, MD and Miranda Orr, PhD
Primary objectives: NAD(+) can be synthesized from dietary intake of its precursors, including nicotinamide riboside, a currently available non-prescription nutritional supplement. In this pilot study, they will conduct an eight week, double-blind, randomized, placebo-controlled trial with this supplement. The investigators will then test the efficacy of NAD(+) supplementation on brain function through cognitive assessment and functional MRI.
Effect of Stress-Busting Program on Caregivers’ Quality of Life, Immunology/Stress Biomarkers and Cellular Aging.
Investigators: Lyda Arevalo-Flechas, PhD and Chih-Ko Yeh, DDS
Primary objectives: The proposed study examines the differences in quality of life (QoL), stress response, and immune function of Hispanic caregivers of persons with dementia, and aims to determine whether a caregiver intervention can effectively improve the QoL and immune function of Hispanic caregivers, including the measurement of the biological response to stress as indicated by immunologic and other pertinent protein markers in blood and saliva from the caregivers.
Identifying Frailty and Determining Outcomes: Setting the Baseline at UHS and STVHCS.
Investigators: Paula Shireman, MD and Sara Espinoza MD
Primary objectives: Frailty is an important predictor of outcome after surgical procedures that is not routinely assessed. Practical measures of frailty must be easy to incorporate into busy clinics with minimal disruption of patient flow and be accompanied by acceptance by the clinic staff as an important component of patient care. Given the changing US demographics, providing patient-centered, cost-effective care for the geriatric population is a national priority. Identification of frailty is the necessary, first step to improving outcomes.
The aims of this proposal are:
1) Determine the association of ethnicity and socioeconomic status on the effectiveness of RAI-A scores in predicting post-operative morbidity and mortality
2) Implement RAI and grip strength screening in Vascular Surgery clinics at the STVHCS and UHS
Pilot study on the use of senolytics in older patients with idiopathic pulmonary fibrosis.
Investigator: Anoop Namibar, MD
Primary objectives: Mayo Clinic and UTHSCSA investigators will conduct parallel pilot studies on the potential use of these senolytic agents in older subjects with IPF and CAVD. The investigators propose the following Specific Aims:
Aim 1: To characterize drug treatment and general disease phenotypes of patients with IPF and CAVD in the UT Health clinical practice.
Aim 2: To determine the safety and tolerability of senolytic drugs in older (60+ years) patients with IPF.
Marmoset gut microbiome and aging.
Investigators: Corinna Ross, PhD and Kelly Reveles, DPharm, PhD
Primary objectives: The specific aims of this proposal are: 1) To characterize the microbiome of young and old marmosets 2) To perform fecal transplants from young to old marmosets and characterize the change in microbiome and to determine whether the transplanted microbiome is stably maintained over the course of 6 months. The data from this pilot examination will contribute to the rapidly expanding knowledge we have regarding marmoset health and aging as well as contribute to future applications for long term investigation of health span interventions to the NIA.
Pilot study evaluating the pharmacokinetics and tolerability of metformin and acarbose in the marmoset.
Investigators: Elizabeth Fernandez*, PhD and Marty Javors, PhD (*early-stage investigator)
Primary objectives: This pilot explores whether marmosets tolerate treatment with either metformin or acarbose, and whether therapeutic blood levels of metformin are achievable in marmosets.
Methylene blue enhancement of fMRI brain activity, memory, and cognition in healthy aging and MCI.
Investigators: Peter Fox, MD, Donald Royall, MD, PhD, Francisco Gonzalez-Lima, PhD, Pavel Rodriguez*, MD, Andrew Bresnen*, PhD, Juan Gutierrez, MD (*early-stage investigators)
Primary objectives: This study explores whether methylene blue (MB) treatment enhances brain memory and cognitive function in elderly patients without and with mild cognitive impairment (MCI).
Metformin for preventing frailty in high-risk older adults.
Investigators: Sara Espinoza*, MD (PI), Chen-Pin Wang*, PhD (Co-PI), Carlos Lorenzo*, MD, Ralph DeFronzo, MD (*early-stage investigators)
Primary objectives: This pilot explored whether metformin in older adults with pre-diabetes prevents or slows the development of frailty; the project continues with R01 funding from NIA.
Lentiviral-mediated delivery of GDF11 in the marmoset.
Investigator: Senlin Li, MD
Primary objectives: This study explores whetherl GDF (growth differentiation factor) 11, expressed from a transgene and secreted by blood cells, leads to the rejuvenation of brain, skeletal muscle, and heart of marmosets.
mTOR inhibition in older subjects: Immune, cognitive and functional consequences.
Investigators: Dean Kellogg, MD, PhD and Ellen Kraig, PhD
Primary objectives: This pilot explores whether treatment of elderly people with rapamycin and acarbose is safe, and whether such treatment mitigates immunologic, cognitive, and physical function phenotypes of aging.
A novel gene therapy to retard motor neuron degenerative disease and sarcopenia.
Investigators: Qitao Ran, PhD and Corinna Ross, PhD
Primary objectives: The investigators seek to develop an adeno-associated viral vector expressing the Gpx4 gene, and then to test the effectiveness of transducing spinal motor neurons with the Gpx4 adeno-associated viral vector in retarding ALS and sarcopenia in mice and marmosets.
For information about human subject studies at UT Health San Antonio, you may visit:
Core Co-Leader: Robert Clark, MD
Core Co-Leader: Randy Strong, PhD