Will We Have a Treatment for Aging?

• Leadership: Steve Albert, PhD, Andrea Rosso, PhD, MPH
• CPOC Resources: Pepper Research Network on Aging, Research Resources

CPOC plays a critical role in training REC investigators in the rationale and application of key methodologies in aging research. The primary focus is to ensure that all trainees are knowledgeable about the clinical syndrome of mobility impairment and falls and the rationale for clinically relevant assessment of balance. Trainees are also oriented to the potential use of existing data for preliminary or independently funded studies and in methods to promote retention. Training can include observation of methods as currently applied in ongoing studies. As part of REC activities, all basic science and non-clinical trainees are required to observe the conduct of core measures in an ongoing study. Please see the REC section of this progress report for more details.

CPOC Activities:

• Engage older adults from the community and long-term care settings in research.
• Provide access to ongoing cohort studies, specimens, clinical trials and existing databases.
• Provide expertise in clinical assessment methodology by providing a standardized set of forms to promote a common data set of core measures for mobility, balance, and falls.
• Utilize noninvasive, portable technology to examine mobility, balance, and physical activity in clinics and in the field through our novel mobile laboratory.
• Provide access to space and equipment for OAIC related studies with our SMART Center.
• Support the research training mission of the Pepper Center.
• Evaluate the functions and productivity of the Core and manage its productivity.
• Collaborate with all the other cores and units within and outside the institution for OAIC related themes.

• Leadership: Toren Finkel, MD, PhD, Stacey Rizzo, PhD

The Biology of Mobility and Aging Core (BMAC) is a new Core within the Pepper Center. It has been established to facilitate the translational gap from basic research at the bench to the clinic, by providing Pepper Center investigators unprecedented access to state-of-the-art instrumentation, resources, and intellectual and technical expertise in aging biology and translational science. The BMAC will foster collaborations of clinicians and basic scientists in order to better enable in-depth interrogation of pathways linking aging “hallmarks” with age-related phenotypes and healthspan indicators. This will ultimately enable clinical trials of novel interventions to preserve mobility and balance in aging populations.

The goal of this new core is to promote both basic-to-human and human-to-basic translation. The BMAC builds on the momentum of the Aging Institute, created several years ago with support from Pitt/UPMC. The BMAC will provide an engine of discovery and innovation to guide and enhance our clinical and translational efforts. Specific emphasis includes using basic science approaches to uncover novel biomarkers that might aid in the treatment of age-related alterations in mobility and balance. Moreover, the BMAC will assist in the development and characterization of innovative pre-clinical animal models that can be used to mechanistically explore the fundamental basis of age-related changes in mobility, gait and balance. Other aspects in which the BMAC will function will be to provide guidance on the use and interpretation of various ‘omic’ technologies. For instance, the BMAC will aid Pepper investigators in the appropriate use of various molecular tools such as single cell RNAseq and metabolomics, which might provide valuable mechanistic insight to complement various ongoing clinical and translational endeavors.

The BMAC will also help Pepper investigators who might wish to pursue any of a number of high throughput screening approaches including whole genome CRISPR-based screens or screens of diverse chemical libraries. Such screens are envisioned to be essential to uncover new molecular targets or novel therapies that might, for instance, improve age-related muscle function. Finally, the BMAC will catalyze our Team Science efforts, as a way of accelerating the adoption of a ‘common language’ between basic, translational and clinical scientists.

• Leadership: Caterina Rosano, MD, MPH, Mark Redfern, PhD
• ISC Resources: The ISC provides skills and techniques to foster understanding of biomechanical, structural, functional, physiological and biological influences on age-related mobility and balance. We have expertise with techniques such as Neuroimaging, Near-Infrared Spectroscopy (NIRS), Biomechanics, and Gait Analysis.

We strive to provide a comprehensive, individualized career development program to prepare future investigators to become leaders in mobility, balance, and aging research. All of the pilot projects that are supported by the ISC, involve at least one other core (DMAIC, REC, PESC, CPOC, BMAC). The ISC interacts with the CPOC to develop assessment tools that are accessible in the clinic and community. The ISC interacts with the DMAIC regarding formats for data entry, pre- processing of data, data quality control, interpretation of findings and novel analytic techniques for complex data. The ISC interacts with REC by providing consultation and training on various instrumentation, and laboratory techniques. The ISC helps REC members apply for small REC pilot funds and interacts with the PESC by providing pre-award consultation, cost estimates and access to key laboratory facilities. The ISC interacts with the BMAC for translational studies.

• Leadership: Subashan Perera, PhD, FGSA, Charity Moore Patterson, PhD, MSPH
• Study Design: We meet with Pepper investigators early in study conception to assist with:
  • Data Analysis
  • Data Management
  • Informatics
  • Center for Health Care: Data Center CTSI
  • Physical Therapy Data Center
  • Biomedical Informatics
  • Computational and systems biology
• Statistical Analysis: We use SAS as our main general purpose statistical software, and Salford Predictive Miner, Stata, SUDAAN, Solas, StatXact, LogXact, PASS, NQuery as needed for specific requirements involving classification/regression trees, frailty models, complex survey data, missing data, exact inference, and sample size/power computations.
  • DMAIC is proficient in providing all standard analytic support such as general (ANOVA, ANCOVA, regression) and generalized (logistic/Poisson/negative binomial variations) linear models, generalized estimating equations and linear mixed model extensions of the above, survival analysis (Cox & frailty models), time series analysis (Box-Jenkings, ARIMA, ARCH) and multivariate methods (factor, cluster, principal component, discriminant, multivariate ANOVA analyses).
• Informatics: DMAIC is available to provide informatics support to Pepper investigators. We assist with capabilities of various databases of the UPMC Health System, MARS, and falls data warehouse. We will assist in merging data across different databases using multiple identifiers; and de-identify the data for research using appropriate methods. Through access to these databases, we provide capabilities for real-time event surveillance such as falls, adverse drug event monitoring and adverse event monitoring in clinical trials.

• REC Leadership: Elsa S. Strotmeyer, PhD, MPH
• Scholar Programs and Opportunities for Young Investigators
• Novice Scholars: This program engages trainees in the research area of balance, mobility and aging early in their development by offering research opportunities in a supportive and enthusiastic environment. The Novice candidates also provide a pipeline for future Pepper Scholars.
  • Candidates must have an interest in some aspect of balance, mobility, and aging, a sponsoring mentor who is involved in the OAIC and defined research goals, including a research project in a related area.
  • Trainees at this initial level must have funding from an existing institutional program. Trainees may come from any of the age-related T32 training grants, the Hartford Center of Excellence, physicians on other funded research training tracks within their specialties, or doctoral or postdoctoral trainees from the Schools of Public Health, Nursing, Allied Health, or Engineering.
• Pepper Scholars: The Pepper Scholar program supports junior faculty trainees who have achieved an initial level of expertise and productivity in an area related to balance, mobility, and aging while they seek their first independent funding.
  • Candidates will generally have completed the bulk of initial didactic training in research methods, have completed and published initial research projects, have a sponsoring mentor and mentoring team, and have a training plan with specific goals and milestones, including a specific research project and plan for submitting a proposal for independent funding.
  • All Scholars must spend at least 75% time in research and are expected to have an individualized training plan that utilizes the resources of the CTSI – ICRE. Scholars will complete an Individualized Develop Plan annually and review with their mentoring team.
• Young Investigators- Transitioning to Independence: This program promotes development of trainees into independent investigators by fostering experiences in leadership and collaboration with other investigators, skills supplementation as desired, and team support and feedback on proposals and manuscripts.
  • Candidates have independent career awards in areas relevant to our theme. They have a sponsoring mentor related to the Pepper Center and a career training plan with specific goals and milestones, including a specific research project.
• Visiting Scholar: This program is to promote development into an independent investigator by fostering experiences in leadership and collaboration with other investigators, skills supplementation as desired, and team support and feedback on proposals and manuscripts.
  • Candidates have independent career awards in areas relevant to our theme.
  • They have a sponsoring mentor related to the Pepper Center and a career training plan with specific goals and milestones, including a specific research project.

• Leadership: Daniel Forman, MD, Aditi U. Gurkar, PhD

The Pilot/Exploratory Studies Core (PESC) promotes and supports innovative multidisciplinary research related to balance, mobility, and aging. The PESC encourages supplements to ongoing studies by funding new and ongoing studies, informing investigators of opportunities for pilot funding supplements, and promotes innovative techniques and methods.

The PESC has partnered with the CTSI and the Aging Institute to increase individual pilot projects.

Investigator: Rocha
Topic: Small molecules to prevent mobility decline

Investigator: Rogers
Topic: Remote physical activity intervention

Investigator: Scheunemann
Topic: Social determinants of health, functional status and health care utilization

Investigator: Torres-Oviedo
Topic: Gait automaticity and locomotor adaptation

Investigator: Farsijani
Topic: Dietary protein, gut microbiome and mobility

• Leadership: Dr. Greenspan, Dr. Newman
• LAC Collaboration: The LAC has fostered and coordinated the research efforts of over 80 Pepper investigators from multiple venues including the School of Medicine, Public Health, Bioengineering, Rehabilitation Medicine, Nursing, Pharmacy, Psychiatry, Neurology, Informatics and Community Health. The LAC insures that the cores and core leaders of the Research Career Development KL2, Clinical and Population Outcomes, Integrative Systems, Data Management, Analysis and Informatics, and Pilot/Exploratory Studies cores coordinate and collaborate with each other.
• The LAC receives valuable input and direction from 4 advisory groups including 1) the External Advisory Committee (national experts), 2) the Institutional Advisory Board (multidisciplinary group of experts on aging from the University of Pittsburgh and UPMC), 3) the Community Advisory Board (members from local health care agencies, IRB, local media, the registry and local leaders) and 4) the REC Advisory Committee (internal and external experts).

• Leadership: Dr. Perera, Dr. Handler, Dr. Rubio
• Study Design: We meet with Pepper investigators early in study conception to assist with:
  • ensuring hypotheses are relevant and testable
  • analysis of preliminary data and sample size and power computations
  • development of the analysis plan, randomization (if applicable)
  • analysis of data
  • interpretation of results
  • generating relevant graphics and text for dissemination of results in presentations and manuscripts
• Statistical Analysis: We use SAS as our main general purpose statistical software, and Salford Predictive Miner, Stata, SUDAAN, Solas, StatXact, LogXact, PASS, NQuery as needed for specific requirements involving classification/regression trees, frailty models, complex survey data, missing data, exact inference, and sample size/power computations.
  • DMAIC is proficient in providing all standard analytic support such as general (ANOVA, ANCOVA, regression) and generalized (logistic/Poisson/negative binomial variations) linear models, generalized estimating equations and linear mixed model extensions of the above, survival analysis (Cox & frailty models), time series analysis (Box-Jenkings, ARIMA, ARCH) and multivariate methods (factor, cluster, principal component, discriminant, multivariate ANOVA analyses).
• Informatics: DMAIC is available to provide informatics support to Pepper investigators. We assist with capabilities of various databases of the UPMC Health System, MARS, and falls data warehouse. We will assist in merging data across different databases using multiple identifiers; and de-identify the data for research using appropriate methods. Through access to these databases, we provide capabilities for real-time event surveillance such as falls, adverse drug event monitoring and adverse event monitoring in clinical trials.

• Screening of deidentified aggregate data. Investigators can search the database using criteria related to mobility status, demographics, or other indicators to determine potential sample sizes available for a proposed study.
• Access to identifiable data for actual recruitment. Studies require formal research approval, including IRB approval and protocol review by the Pepper registry committee. Investigators then have access to individual subject data in an automated web-based application. Investigators receive a password, specify study inclusion/exclusion criteria on a secure webpage, and download a current database of potentially eligible respondents.
• Researchers using the community registry need to include the registry in their IRB protocol, which can be found in PittPRO section Recruitment Methods – #2.

• Scholar Programs and Opportunities for Young Investigators
• Novice Scholars: This program engages trainees in the research area of balance, mobility and aging early in their development by offering research opportunities in a supportive and enthusiastic environment. The Novice candidates also provide a pipeline for future Pepper Scholars.
  • Candidates must have an interest in some aspect of balance, mobility, and aging, a sponsoring mentor who is involved in the OAIC and defined research goals, including a research project in a related area.
  • Trainees at this initial level must have funding from an existing institutional program. Trainees may come from any of the age-related T32 training grants, the Hartford Center of Excellence, physicians on other funded research training tracks within their specialties, or doctoral or postdoctoral trainees from the Schools of Public Health, Nursing, Allied Health, or Engineering.
• Pepper Scholars: The Pepper Scholar program supports junior faculty trainees who have achieved an initial level of expertise and productivity in an area related to balance, mobility, and aging while they seek their first independent funding.
  • Candidates will generally have completed the bulk of initial didactic training in research methods, have completed and published initial research projects, have a sponsoring mentor and mentoring team, and have a training plan with specific goals and milestones, including a specific research project and plan for submitting a proposal for independent funding.
  • All Scholars must spend at least 75% time in research and are expected to have an individualized training plan that utilizes the resources of the CTSI – ICRE. Scholars will complete an Customized Career Development Plan annually and review with their mentoring team.
• Young Investigators- Transitioning to Independence: This program promotes development of trainees into independent investigators by fostering experiences in leadership and collaboration with other investigators, skills supplementation as desired, and team support and feedback on proposals and manuscripts.
  • Candidates have independent career awards in areas relevant to our theme. They have a sponsoring mentor related to the Pepper Center and a career training plan with specific goals and milestones, including a specific research project.
• Visiting Scholar: This program is to promote development into an independent investigator by fostering experiences in leadership and collaboration with other investigators, skills supplementation as desired, and team support and feedback on proposals and manuscripts.
  • Candidates have independent career awards in areas relevant to our theme.
  • They have a sponsoring mentor related to the Pepper Center and a career training plan with specific goals and milestones, including a specific research project.
• REC Leadership Workshops: Workshops to foster leadership and cultural coaching are held twice monthly. Upcoming workshop topics and details can be found on our calendar page.