WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE
Claude D. Pepper Older Americans Independence Center

Stephen Kritchevsky, Ph.D.
Principal Investigator
  336-713-8548   skritche@wakehealth.edu
Dalane Kitzman, MD
Co-Principal Investigator
    dkitzman@wakehealth.edu
Kimberly Kennedy, MS, CCRC
Program Administrator
  336-713-8567   kkennedy@wakehealth.edu
     
CENTER DESCRIPTION

The WF OAIC Leadership and Administrative Core (LAC) sets the scientific direction, optimizes administrative and fiscal operations, and ensures the scientific integrity and coherence of the WF OAIC. LAC co-leaders Drs. Kritchevsky and Kitzman will use a proven collaborative leadership model that fosters operational efficiency, high productivity, and innovative translational and multidisciplinary research focused on our theme, “Integrating pathways affecting physical function for new approaches to disability treatment and prevention”.

The Specific Aims of the Leadership and Administrative Core are to:

1.  Provide overall scientific leadership and direction for the WF OAIC. The LAC co-leaders will synthesize information regarding the local and national research environment with input from the OAIC Executive Committee, the OAIC External Advisory Board, the REC Advisory Committee and WF’s senior administrative leadership to guide the direction of the OAIC through:  the mix of Core services; the focus of research development projects; the tailoring of pilot award RFAs; interactions with the OAIC Coordinating Center, other OAICs and other aging-focused research centers; and the selection of early- career faculty for Research Education Component (REC) support. The LAC will integrate WF OAIC Core activities to advance the OAIC’s scientific agenda, improve efficiency, and foster translation between basic and clinical research.

2. Efficiently manage the resources of the WF OAIC in compliance with applicable institutional and NIA/NIH policies. The LAC will: 1) provide administrative and budgetary support to the WF OAIC according to OAIC priorities; 2) seek additional institutional resources to extend the scope of its activities; 3) arrange for the scientific review of pilot and research development projects and candidates seeking REC support; 4) monitor all OAIC activities for timely completion and achievement of targeted goals and milestones, and intervene to remove roadblocks or (if necessary) redirect resources; and 5) assure all OAIC-supported activities follow federal and institutional rules, regulations, and guidelines and promote the responsible conduct of research and participant safety.

3. Increase WF OAIC’s impact by attracting new investigators, capturing new resources, and translating findings beyond traditional research settings. The LAC will attract new researchers and research capabilities to OAIC-supported research by engaging the local and regional academic communities, in coordination with resources from WF’s Sticht Center for Healthy Aging and Alzheimer’s Prevention, the Section of Gerontology and Geriatric Medicine, and other academic and service units.  The LAC will also promote the NIA’s goals for the OAIC program by translating its research to affect the clinical care of older adults and the health and well-being of older adults in the community. 

During the current cycle, the WF OAIC achieved high productivity and innovation, and enhanced its strategic positioning and prominence within Wake Forest and enhanced its local and national impact.  Compared to the previous cycle, publication productivity was increased 5% and OAIC-related extramural funding increased 91%. The outstanding productivity of OAIC investigators occurred despite the challenging funding environment and is attributable (in part) to our innovative strategies to promote efficiency (e.g., thematic alignment, the OAIC Integrated Aging Studies Databank and Repository), and the LAC’s success in leveraging $4.3 million in institutional funds in support of the OAIC mission. 

WF OAIC involvement was critical in securing high-impact awards that enhance the breadth and depth of research resources available to the OAIC, including a new CTSA and a new Alzheimer’s Disease Core Center.  As an Associate Director of the Wake Forest Clinical and Translational Science Institute and director of its KL-2 program, Dr. Kritchevsky aligned CTSI resources with the OAICs for their mutual benefit.  His role as Associate Dean for Research Development provides him with influence over WF’s research priorities.  Locally, the OAIC has successfully expanded our research partnerships to deliver interventions in innovative settings (Meals-on-Wheels, Agricultural Extension Service, YMCA’s and Continuing-Care communities). WF OAIC leaders have been national advocates for the OAIC’s mission and have helped develop multi-centered trials testing hypotheses generated from OAIC work (e.g. LIFE, ENRGISE, PCORI/STRIDE) and pivot large multi-center trials towards OAIC relevant outcomes (e.g., SPRINT, Look AHEAD).  The WF OAIC, under the leadership of Drs. Kritchevsky and Kitzman, will use OAIC support to sustain the LAC’s continual innovation through the 2018-2023 cycle.

To address these objectives our OAIC is composed of seven cores, which currently supports 5 REC Scholars, 17 clinical studies (all which are funded by the NIH), 2 research development projects, and 8 pilot studies.


CORES
Leadership and Administrative Core (LAC)
Leader 1:    Stephen Kritchevsky, PhD   skritche@wakehealth.edu
Leader 2:    Dalane Kitzman, MD   dkitzman@wakehealth.edu
The Leadership and Administrative Core is responsible for scientific leadership and direction of the center. It coordinates the functions of the OAIC cores and projects in order to facilitate communication and foster translation between basic and clinical research and ensure access of investigators to core resources. It assures the coordination of OAIC resources and functions with other research and training grants and institutional resources. It is supported by the OAIC Executive Committee, the Joint Scientific Review Panel, and the External Advisory Committee. The core communicates with other OAICs and the NIA and fosters collaborations with other OAICs including UTMB, University of Maryland and Duke. Maintains the OAIC web-based tracking and monitoring system and promotes the use of uniform assessment batteries in all OAIC supported studies. The LAC works with Core leaders to identify, review, and support projects and activities which serve to advance the scientific goals of the OAIC. The LAC and Executive Committee actively identify promising projects and REC candidates through informal networks, review of all new faculty hires at WF, and all new grant awards to WF faculty. WF OAIC overarching resource allocation priorities are based on: 1) scientific merit; 2) theme relevance; 3) REC scholar/junior faculty involvement; 4) Pilot/Exploratory study support; 5) research development projects; and 6) externally supported projects. This priority maintains our thematic coherence and enhances support for projects that may need it.

Research Education Component (REC)
Leader 1:    Stephen Kritchevsky, PhD   skritche@wakehealth.edu
Leader 2:    Denise Houston, PhD   dhouston@wakehealth.edu
Leader 3:    Heidi Klepin, MD   
The Research Education Component (REC) continues to promote the development of future research leaders in the area of focus of this OAIC application, integrating pathways affecting physical function for new approaches to disability treatment and prevention. The core emphasizes development of skills for translating basic findings into clinical research, and clinical findings into basic research. Resources of this core are integrated with other external sources for career support, such as NIH career development and research awards, fellowships, and non-NIH career and research awards. Resources of the REC are also leveraged with assets of the Wake Forest Clinical and Translational Science Institute (CTSI); Dr. Kritchevsky is a Core Faculty member of the CTSI’s KL2 program. The CTSI has a Translational Research Academy, a Mentor Academy, and a K and R Award Writer’s Series, which provide added value to the REC through courses, facilitation of grants, navigating regulations, and evaluating competencies. All REC scholars are encouraged to participate in the Translational Research Academy to help optimize the relative contributions of the CTSI and REC programs. The REC co-leaders are Drs. Kritchevsky and Houston; Dr. Klepin, REC leadership intern, will specifically recruit and advise promising clinical faculty. Dr. Kritchevsky is a national leader in aging research, whose expertise spans the translational spectrum from basic science to policy formulation. Dr. Houston is a national leader in nutrition and aging research with expertise in both epidemiologic studies and clinical trials. Dr. Klepin is a national leader in geriatric oncology with expertise in conducting patient-oriented research, including both pharmacologic and behavioral interventions. Each of the Core Leaders is accomplished in interdisciplinary and team-based research, and well positioned to assure that REC programs and activities are well integrated with other internal and external career development activities. All REC projects continue to utilize Pepper Core support to signify the integration of resources and disciplines. This includes: Ellen Quillen, PhD (Integrative Biology Core) and Atalie Thompson, MD, MPH (Biostatistics and Data Management Core and Clinical Research Core). The REC currently supports five REC scholars which includes two REC scholars that began in the summer/fall of 2021 (Quillen, Thompson) and three new REC scholars (Genesio Karere, PhD; Lindsay Reynolds, PhD; and Jaime Hughes, PhD) that started in April 2022. The three new REC scholars were selected in response to an RFA for REC scholars distributed across the institution in October 2021. Two REC developmental scholars (Chinenyenwa Usoh, MD, and Philip Kramer, PhD) were also selected with the purpose of helping them refine and develop their research ideas and strengthen their research portfolios.

Pilot and Exploratory Studies Core (PESC)
Leader 1:    Dalane Kitzman, MD   dkitzman@wakehealth.edu
Leader 2:    Tom Register, PhD   register@wakehealth.edu
Leader 3:    Jingzhong Ding, MD, PhD   jding@wakehealth.edu
Effective pilot and exploratory studies (PES) play a critical role in the development of successful, externally-funded research proposals, particularly for early stage investigators who often lack other means to obtain preliminary data. The Wake Forest OAIC Pilot and Exploratory Studies Core (WF PESC) proposes to continue our coordinated, multi-faceted group effort to promote PESs, and to further innovate to optimize our processes. Through support from the OAIC grants, Wake Forest University has been very active in efforts to enhance aging related research activities. These activities have focused on the mechanism, treatment and outcomes associated with functional decline and disability and have had a profound impact on the research culture at our institution with greater awareness and interest in addressing these important yet understudied issues of geriatric research.

The overall goal of the WF OAIC PESC is to develop key information needed for the design of definitive, externally funded, translational research studies that promote the WF OAIC mission of advancing our understanding of pathways influencing physical function and developing new approaches to disability prevention and treatment.

This will be achieved by executing the following Specific Aims to:

1) Identify and promote promising key areas of research
2) Identify and recruit talented investigators from complementary fields to focus on OAIC-themed aging research
3) Solicit and facilitate competitive research proposals and conduct peer review to select those with the best science and career development opportunities
4) Coach and mentor investigative teams to maximize the quality of research proposals and projects
5) Team with other WF OAIC cores to facilitate successful completion of the selected pilot projects and mentor junior early career investigators to advance their development as successful translational scientists

Continuously evaluate, refine, and optimize OAIC PESC processes and procedures.

Clinical Research Core (CRC)
Leader 1:    Jack Rejeski, PhD   rejeski@wfu.edu
Leader 2:    Anthony Marsh, PhD   marshap@wfu.edu
Leader 3:    Jeff Williamson, MD, MHS   jwilliam@wakehealth.edu
Leader 4:    Kristen Beavers, PhD   beaverkm@wfu.edu
The Clinical Research Core (CRC) provides institution-wide guidance on the design and conduct of clinical research consistent with the WF OAIC theme (present and past) and involving older adults. The CRC also performs validated, standardized assessments of physical and cognitive function, strength, and disability. Assistance is provided to investigators at all levels of experience and all sizes of research studies with integration of these OAIC measures into their research involving older adults. The Core’s scientific focus is the advancement of physical function based clinical research methods and the design, implementation, and evaluation of interventions designed to measure whether specific interventions developed in this or other cores preserve the independence of older adults. Functional assessment instruments and trial design encompass both community and clinic-based settings. Additionally, members of the core are involved in cross-disciplinary translational research with other cores within the center. The overall hypothesis for this CRC is that the inclusion of efficient, standardized measures of functional assessment will promote translation of the OAIC research into clinical research and care through improved understanding of function as both a risk factor and an outcome (see below). The Core also includes both 1) a recruitment unit and 2) a muscle and adipose tissue biopsy unit for OAIC supported studies. In addition, if including aging-related measures is required as part of specific studies, the Core supported staff will assist investigators by training them or their staff and/or collecting these assessments. Currently the standard assessment battery includes: 1. Anthropometry (Height, Body Mass, Abdominal Circumference) 2. Grip strength (Jamar hand grip dynamometer) 3. Lower extremity muscle power (Keiser knee extension and leg press) 4. The Short Physical Performance Battery (SPPB: three tests of physical function - standing balance, usual pace gait speed over 4 meters, time to rise from a chair and sit down five times) 5. 400 meter walk test (400MWT: study specific protocols for either usual or fast pace gait speed) 6. Pepper Assessment Tool for Disability (PAT-D: self-report instrument) 7. Mobility Assessment Tool – short form (MAT-sf: 10 or 12-item computer based self-report assessment of mobility using animated video clips) 8. Digit Symbol Substitution Test (DSST: validated cognitive assessment that is strongly correlated with walking speed) 9. Montreal Cognitive Assessment© (MoCA: global cognitive assessment that aids in interpreting DSST performance) The core also has the capacity to assess muscle strength of various muscle groups (Biodex isokinetic dynamometer), gait speed and spatiotemporal parameters of gait (GAITRite instrumented mat), and postural sway descriptors (AMTI portable force platform).

BioImaging
Leader 1:    Leon Lenchik, MD   llenchik@wakehealth.edu
Leader 2:    Christina Hugenschmidt, PhD   chugensc@wakehealth.edu
Leader 3:    Ashley Weaver, PhD   asweaver@wakehealth.edu
This core supports independently funded studies, pilot studies, and research development studies in the accurate in vivo measurement of body composition, specifically focusing on skeletal muscle mass and composition, fat mass and distribution, and bone mineral density. This core collaborates with other OAIC cores in the development of new, multidisciplinary, and translation research projects directed at elucidating the etiology, consequences, prevention and treatment of sarcopenia and its sequelae. The BRC has contributed to the success of the WF OAIC by helping to quantify structural and functional tissue-related measures, developing novel bio-imaging techniques, integrating imaging assessments with other OAIC cores, and using imaging technologies for studies of physical function and disability in older persons. The BRC has also provided early-career and experienced investigators access to a broad range of imaging methods relevant to disability and age-related physical decline including dual x-ray absorptiometry (DXA), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasonography (US) as well as access to expertise and mentoring in bio-imaging including image acquisition, analysis, interpretation, archival, and dissemination. The Bioimaging Resource Core (BRC) has contributed to the success of the WF OAIC by helping to quantify structural and functional tissue-related measures, integrating imaging assessments with other OAIC cores, and using imaging technologies for studies of physical function and disability in older persons. The BRC has also provided early-career and experienced investigators access to a broad range of imaging methods relevant to age-related physical decline including dual x-ray absorptiometry (DXA), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasonography (US) as well as access to expertise and mentoring in bio-imaging including image acquisition, analysis, interpretation, archival, and dissemination. Over the past year, the BRC has added an emphasis on expanding the imaging infrastructure. The infrastructure initiative has two parts: 1) updating hardware and software and harmonizing archiving with other OAIC and ADRC cores to increase access to data already collected and 2) adding new bone imaging capability to the suite of imaging techniques available to OAIC investigators. The BRC received an administrative supplement (in response to NOT-AG-17-008 and PA-16-287) to develop research on Alzheimer’s disease and Alzheimer’s-related dementias (ADRD). The goal was to harmonize imaging data workflow between the WF OAIC and WF ADRC. In the past year, the BRC made progress on: 1) archiving of past imaging studies using a newly acquired Vendor Neutral Archive (VNA), 2) harmonizing imaging data storage, processing, and archiving between the OAIC and ADRC, and 3) harmonizing imaging data request process between OAIC and ADRC. Such harmonization will allow investigators to ask cutting-edge questions about the brain-body integration including the trajectory of physical decline in people with ADRD and the trajectory of cognitive decline in older adults with mobility disability, obesity, and frailty.

Biostatistical Design and Analysis Core (BIC)
Leader 1:    Iris Leng, PhD   ileng@wakehealth.edu
Leader 2:    Nicholas Pajewski, PhD   npajewsk@wakehealth.edu
Leader 3:    Dan Beavers, PhD   dbeavers@wakehealth.edu
The goal of the Wake Forest OAIC Biostatistics and Research Information Systems Core (BIC) is to build on our outstanding success in biostatistical collaboration and to expand a broad class of statistics/informatics tools tailored to research in aging. The BIC team has highly qualified investigators/staff with expertise in design and management of observational, pilot, and interventional studies; centralized and decentralized data management; forms design and data processing, psychometrics; statistical analysis of data from multiple study designs; and development of novel statistical methods. The BIC team is committed to the WF OAIC’s programmatic aims to: (1) discover new common pathways contributing to age-related declines in physical function and disability; (2) develop, evaluate, and refine strategies for disability treatment and prevention; (3) translate proven strategies beyond traditional research environments; and (4) train the next generation of research leaders focused on disability treatment and prevention. The BIC provides expertise and critical infrastructure essential to the mission of the WF OAIC, and promotes efficiency through centralized data management. BIC members will play a key role in study design, analysis, and interpretation for WF OAIC projects, will be integral members of mentoring teams for REC Scholars and early-stage faculty, and continue their intellectual contributions that strengthen research on aging through the development of novel measurement, statistical, and research informatics tools. During the past year, members of the Biostatistics and Research Information Systems Core (BIC) have continued to provide support for numerous studies performed within the WFU OAIC. Efforts include developing web-based data entry systems for individual studies, harmonizing common measurements taken across multiple studies, performing analyses of pilot/developmental studies and existing data bases, and collaborating on the development of pilot studies and grant submissions resulting from WFU OAIC pilot studies. In addition, faculty in the Core continue to be involved with mentoring committees for REC fellows, collaboration on career development award submissions, reviewing pilot studies and applications of prospective REC fellows. During the past year, members of the BIC collaborated with WFU OAIC investigators in the submission of several R01s, a U24, and a K76 grant. During the past year, members of the BIC collaborated with WFU OAIC investigators in the submission of several R01s, a U24, and a K76 grant. As of October 2021, the BIC has also undergone a planned change in leadership, with Drs. Miller and Ip stepping down from their roles.

Integrative Biology Core
Leader 1:    Barbara Nicklas, PhD   bnicklas@wakehealth.edu
Leader 2:    Osvaldo Delbono, PhD   odelbono@wakehealth.edu
Leader 3:    Jamie Justice, PhD   jjustice@wakehealth.edu
Over the past year, the Integrative Biology Core (IBC) advanced the science of our OAIC by adding biological measures to facilitate translational research for OAIC investigators and by advising and mentoring REC scholars and early-career faculty. We also continued maintenance of our centrally collected and stored Biological Specimen Repository from aging-related studies. The Core provided resources and personnel in support of several externally-funded studies (SOMMA, HALLO-P, U01 Aging Biomarkers, SECRET2, VARIA, INVEST, UPLIFT, B-NET, HOPE and EMPOWER), and externally-funded and OAIC-supported pilots. Core Resource Use and Development of New Services: Repository, Biomarker, and tissue biopsy services—IBC personnel assist study investigators with the proper collection, transfer, and central storage of human biological tissue specimens and facilitate their later use in ancillary studies by other investigators. In the past year the Core supported labeling, tracking and storage of blood samples from participants enrolled in 6 externally-funded studies (INVEST, SOMMA, B-NET, SECRET2, HOPE, and UPLIFT), and assisted with collection, processing, and storage of muscle (SOMMA) and adipose tissue (SOMMA). The Core also expanded its biomarker services through purchase of two instruments for biomarker determination: Ella SimplePlex and Luminex LX200. Ella SimplePlex is a semi-automated device with integrated cartridge system used for targeted biomarkers – which will form the basis for an expanded ‘Pepper Common Battery’ for biomarkers, and Luminex LX200 has advanced multiplexing capability that permits a discovery-based biomarker approach. The two systems work well in tandem, providing industry-standard biomarker multiplexing via Luminex LX200 which can be used to identify specific markers for analysis using Ella SimplePlex. Resources and personnel advanced the science of our OAIC theme by adding measures to externally-funded studies and pilots to facilitate translational research for OAIC investigators, and by advising and mentoring of the REC scholars. In the past year, the Integrative Biology Core (IBC) advanced the science of our OAIC by adding biological measures to facilitate translational research for OAIC investigators, and by advising and mentoring REC scholars and early-career faculty. We also continued maintenance of our centrally collected and stored Biological Specimen Repository from aging-related studies. The Core provided resources and personnel in support of several externally-funded studies (SOMMA, HALLO-P, U01 Aging Biomarkers, SECRET2, VARIA, INVEST, UPLIFT, B-NET, HOPE and EMPOWER), and externally-funded and OAIC-supported pilots.

CAREER DEVELOPMENT
REC Scholar, Research & Grants Funded During Pepper Supported Time Years /
Publications
 
Lindsay Reynolds, PhD
Assistant Professor / Department of Epidemiology and Prevention
Dietary Patterns and Biological Aging in the Women’s Health Initiative
2022-2024 /
0 (total)
0 (1st/Sr)
 
Genesio Karere, PhD
Assistant Professor / Department of Internal Medicine, Section on Molecular Medicine
MicroRNA biomarkers and pathways underlying response to exercise intervention in older adults
2022-2024 /
0 (total)
0 (1st/Sr)
 
Jaime Hughes, PhD
Assistant Professor / Department of Implementation Science
Promoting healthy sleep-wake behaviors across a 24-hour cycle in frail older adults
2022-2024 /
0 (total)
0 (1st/Sr)
 
Ellen Quillen, PhD
Assistant Professor / Department of Internal Medicine, Section on Molecular Medicine
A multiomic approach to profiling muscle contractility and mobility in healthy adults
  • Wake Forest Pepper Pilot award: Monkeys, muscle, and mobility: a multi-omic approach to understanding the biology of muscle aging (1/22 – 12/22)

2021-2023 /
0 (total)
0 (1st/Sr)
 
Atalie Thompson, MD, MPH
Assistant Professor / Department of Ophthalmology, Section on Glaucoma
Exploring visual impairment and physical dysfunction in older adults
2021-2023 /
0 (total)
0 (1st/Sr)
 

Past Scholars
Kathryn Callahan, MD, MS, Gerontology and Geriatric Medicine (2014-2018)
Candace Parker-Autry, MD, Obstetrics-Gynecology (2015-2019)
Rita Bakhru, MD, MS, Pulmonary, Critical Care, Allergy and Immunologic Diseases (2016-2021)
Jamie Justice, PhD, Gerontology and Geriatric Medicine (2017-2018)
Amber Brooks, MD, Anesthesiology (2017-2018)
Sam Lockhart, PhD, Gerontology and Geriatric Medicine (2018-2019)
Hariom Yadav, PhD, Molecular Medicine (2019-2021)
Jason Fanning, PhD, Health and Exercise Science (2019-2021)

PILOT/EXPLORATORY PROJECTS (8 Pilot Projects Listed)
1. Project Title: PESC 2018.1 Evaluation of Blood-Based Biomarkers of Biological Aging in Heart Failure with preserved Ejection Fraction (HFpEF).
  Leader: Jamie Justice, PhD (Geriatrics)
 

A new generation of clinical trials is being designed to test the Geroscience Hypothesis: that targeting the biology of aging will help maintain function and prevent or delay the onset of age-related chronic diseases, including heart failure with preserved ejection fraction (HFpEF). Biomarkers serve critical roles in clinical trials as surrogate endpoints and by providing evidence that the intervention is appropriately influencing the underlying biology. A utility set of blood-based biomarkers of aging for use in geroscience-guided clinical trials targeting incidence of age-related chronic disease and death has been identified, and includes IL-6, CRP, TNF-Receptor II, GDF15, IGF-1, Insulin, Cystatin C, NT-proBNP, and HbA1c. However, this biomarker set has not yet been tested; this limits development, analysis, and clinical trial planning. Further, no study has examined the intervention effects on broad multi-system biomarkers of biological aging in HFpEF. Such an investigation could provide insights into potential mechanisms and future therapeutic targets in HFpEF while providing crucial evaluation of blood-based biomarkers proposed for clinical trials targeting biological aging.

The research aims of this Pepper Pilot are to 1) measure differences in biomarkers of biological aging in HFpEF patients compared with age-similar healthy adults; 2) determine if the biomarkers of biological aging are associated with physical and cardiovascular function, adjusting for age, sex, adiposity; 3) estimate changes in biomarkers of biological aging over time (controls) and following a diet and exercise intervention in overweight and obese adults with HFpEF. The research aims will leverage a specimen repository from the WFSM Aging Center: de-identified patient records and cryopreserved samples in HFpEF patients previously enrolled in SECRET (100 at baseline, 76 at follow-up), and 64 adults in the Healthy Aging cross-sectional cohort. Well-justified biomarkers of biological aging (IL-6, TNFa-Receptor II, CRP, GDF15, insulin, IGF1, cystatin-C, NT-proBNP, and HbA1c) will be measured. In conjunction with this we have organized a Pepper OAIC Biomarkers Working Group that cuts across multiple Wake Forest OAIC cores to evaluate study progress, inform rigorous measurements, balance resource use, develop an analytic approaches and biomarker indices, and offer scientific consultation and engagement of local studies involving biomarkers of biological aging. 

We leveraged the WF OAIC biorepository to measure a consensus-derived panel of blood-based biomarkers of aging and constructed a geroscience-guided biomarker index (TAME-BI) for the first time in a clinical trial. We measured IL-6, TNF-a-receptor-I, growth differentiating factor-15, cystatin C, and N-terminal pro-b-type natriuretic peptide in a 20-week randomized trial of caloric restriction (CR), aerobic exercise (EX), CR+EX, or attention-control in 88 patients (67±5years) with heart failure with preserved ejection fraction (HFpEF). We calculated TAME-BI (analyte levels ranked, binned by quintile, and summed) and found a time×treatment interaction for improved TAME-BI with intervention (p=0.05) and detected associations between change in TAME-BI and change in six-minute walk distance (r= -0.24), usual walk speed (r= -0.23), and left ventricular relative wall thickness (r= 0.31). In sum, CR+EX intervention improves TAME-BI and changes in TAME-BI are associated with changes in functional measures in older HFpEF patients. 

 
2. Project Title: PESC.2019.1 Isolation and molecular characterization of exosomes secreted by visceral adipose tissue.
  Leader: Gagan Deep, PhD (Cancer Biology)
  The goal of this project is to isolate and characterize visceral adipose tissue (VAT) specific exosomes based on their unique surface markers from blood plasma/serum. Dr. Deep’s laboratory has developed novel techniques and tools to identify tissue specific exosomes, and these established methods will be used to identify VAT-specific exosomes as outlined in following specific aims: Specific Aim I. To identify unique proteins on the surface of exosomes isolated from visceral adipose tissue in mouse and nonhuman primate (NHP) models. Specific Aim II. To isolate and characterize VAT-derived exosomes (VATExo) from blood in mouse and NHP models. Specific Aim III. To isolate and characterize VATExo from the blood of NHP and humans. The long term objective is todevelop blood based VAT-specific exosomal biomarkers to allow noninvasive evaluation of visceral adipose tissue depot to provide novel molecular insights into the biology of this important tissue as well as help us to better understand VAT’s role in various diseases. The successful identification of VAT-derived exosomes from this study will be used as proof of concept for major NIH grants where we will functionally characterize the VAT exosomes in more detail for their “cargo” (including protein, lipids, metabolites, mRNA and miRNA) in order to explore relationships with physical function, frailty, heart failure with preserved ejection fraction, and other phenotypes as well as responses to exercise, diet modification, and other interventions. Novel methods have been developed that will be useful for several studies.
 
3. Project Title: PESC.2019.2 Is Restoring Protein Homeostasis A Viable Therapy For Age-Related Osteoarthritis?
  Leader: Raghunatha Yammani, PhD (Internal Medicine, Molecular Medicine)
  This Pepper pilot's overall goal is to determine the role of proteostasis in age-related OA. To achieve our aim, we will administer a small molecule chemical chaperone 4-phenyl butyric acid (PBA) to 18 months -old mice to restore proteostasis and examine age-linked severity osteoarthritis. There was a delay in starting the project on time due to COVID 19 related shut down of research activities. Yet, good progress has been made in accomplishing the goals described in the pilot application. Eighteen months old (10 male and 10 female) C57BL6 mice were divided into two groups. Group 1 mice receive (0.5mg/kg body) of phenyl butyric acid (PBA) in drinking water, and Group 2 mice received just water. We plan to administer PBA to mice for 20 weeks and collect their knee joint and analyze for cartilage lesion and OA. We also plan to collect tissues other than knee joints, including heart, lung, brain, liver, and blood from mice for tissue bank available to other investigators. Mice on the PBA showed decreased cartilage lesions and improved matrix production compared to the untreated group, evidenced by the ACS score and SafarinO staining. qPCR analysis showed that treatment with decreased mRNA expression of CHOP, an ER stress marker, and pro-apoptotic molecule and increased expression of ATG5, a key component of autophagy system. Additionally, PBA also modulated the gut microbiomes including increased microbiome diversity indices and phylogenetic abundance of beneficial bacteria. These results demonstrate that ER stress plays a significant role in primary OA, and PBA reduces OA by reducing ER stress and beneficially modulating the microbiome. This study demonstrates that alleviating ER stress improved autophagy, matrix production, and decreased cartilage lesions in aged mice. Treatment with PBA also beneficially modulated the microbiome. Taken together, our study demonstrated that targeting ER stress could be a therapeutic approach for primary OA. This data has been submitted as an abstract to international scientific meeting (OARSI 2022, Berlin, Germany). Additionally, we are planning to submit our finding to the journal of Osteoarthritis and cartilage.
 
4. Project Title: PESC 2020.1 Application of the Novel D3Cr Dilution Method to Better Understand Weight Loss Associated Changes in Muscle Mass and Physical Performance Among Older Adults with Obesity
  Leader: Kristen Beavers, PhD (Health & Exercise Science)
  The number of older adults living with obesity is growing at an unprecedented rate. Intentional weight loss (WL) can reverse obesity but concerns develop as WL decreases muscle mass. Counter-intuitively, despite decreased muscle mass; older adults can significantly improve muscle strength, physical performance, and mobility following intentional WL. We posit these paradoxical observations originate from indirect bioimaging methods commonly used to approximate muscle mass in clinical research. In contrast to these methods, the D3-Creatine (D3Cr) dilution method directly measures whole-body muscle mass. Consequently, D3Cr muscle mass displays stronger associations with physical function (i.e. strength, physical performance, and mobility) than dual energy x-ray absorptiometry (DXA) lean mass. However, given the novelty of this method, D3Cr muscle mass has not been examined in an intentional WL RCT; thus, the effects of intentional WL on changes in D3Cr muscle mass remain unclear. To address this knowledge gap, and as an appropriate next step in this line of research, we propose to add the D3Cr muscle mass measure to the ongoing NIA and Claude D. Pepper Older Americans Independent Center supported RCT (NCT04076618), Incorporating Nutrition, Vest, Education and Strength Training trial (INVEST). This pilot will leverage the current INVEST assessment schedule to add the D3Cr muscle mass measure at baseline and six-months. The primary objective of this pilot is to determine the feasibility of the D3Cr muscle mass measure as part of a clinical WL trial. We hypothesize this method for measuring muscle mass will be feasible among participants enrolled in INVEST. Additionally, our secondary objectives aim to (i) quantify the associations between six-month change in D3Cr muscle mass and change in 1) physical function, and 2) computed tomography (CT) muscle density and cross-sectional area (CSA), and DXA lean mass among 30 INVEST participants and (ii) examine the ability of baseline D3Cr muscle mass, CT muscle density and CSA, and DXA lean mass to predict six-month change in physical function among 90 INVEST participants. Overall, we hypothesize stronger associations will be observed between change in D3Crmuscle mass and physical function, compared to DXA and CT; and that baseline D3Cr muscle mass will predict intervention-related changes in muscle physical function; and, to a greater degree than DXA or CT parameters. These data will provide first of its kind data identifying the feasibility of the D3Cr method in a WL trial, support a prior R01 application (AG070169; 35%; MPIs: Cawthon/K. Beavers), and provide a unique training opportunity for Dr. Miller (T32 AG033534).The number of older adults living with obesity is growing at an unprecedented rate. Intentional weight loss (WL) can reverse obesity but concerns develop as WL decreases muscle mass. Counter-intuitively, despite decreased muscle mass; older adults can significantly improve muscle strength, physical performance, and mobility following intentional WL. We posit these paradoxical observations originate from indirect bioimaging methods commonly used to approximate muscle mass in clinical research. In contrast to these methods, the D3-Creatine (D3Cr) dilution method directly measures whole-body muscle mass. Consequently, D3Cr muscle mass displays stronger associations with physical function (i.e. strength, physical performance, and mobility) than dual energy x-ray absorptiometry (DXA) lean mass. However, given the novelty of this method, D3Cr muscle mass has not been examined in an intentional WL RCT; thus, the effects of intentional WL on changes in D3Cr muscle mass remain unclear. To address this knowledge gap, and as an appropriate next step in this line of research, we propose to add the D3Cr muscle mass measure to the ongoing NIA and Claude D. Pepper Older Americans Independent Center supported RCT (NCT04076618), Incorporating Nutrition, Vest, Education and Strength Training trial (INVEST). This pilot will leverage the current INVEST assessment schedule to add the D3Cr muscle mass measure at baseline and six-months. The primary objective of this pilot is to determine the feasibility of the D3Cr muscle mass measure as part of a clinical WL trial. We hypothesize this method for measuring muscle mass will be feasible among participants enrolled in INVEST. Additionally, our secondary objectives aim to (i) quantify the associations between six-month change in D3Cr muscle mass and change in 1) physical function, and 2) computed tomography (CT) muscle density and cross-sectional area (CSA), and DXA lean mass among 30 INVEST participants and (ii) examine the ability of baseline D3Cr muscle mass, CT muscle density and CSA, and DXA lean mass to predict six-month change in physical function among 90 INVEST participants. Overall, we hypothesize stronger associations will be observed between change in D3Crmuscle mass and physical function, compared to DXA and CT; and that baseline D3Cr muscle mass will predict intervention-related changes in muscle physical function; and, to a greater degree than DXA or CT parameters. These data will provide first of its kind data identifying the feasibility of the D3Cr method in a WL trial, support a prior R01 application (AG070169; 35%; MPIs: Cawthon/K. Beavers), and provide a unique training opportunity for Dr. Miller (T32 AG033534).
 
5. Project Title: PESC.2020.2 Development of a Nonhuman Primate Model of Age-Related Sleep Changes & Physical Decline
  Leader: Carol Shively, PhD, Brett Frye, (Pathology/Comparative Medicine, Primate Center)
  Physical decline, poor sleep, and social isolation are characteristics of many older Americans, and these conditions are linked to increased morbidity and mortality. While associations are observed between all three, whether they have causal relationships is poorly understood. Poor sleep and physical decline have been associated in several cross sectional studies, whereas prospective/longitudinal studies are rare and often based on self-reports of sleep quality. Social isolation predicts poor sleep, but recent evidence suggests that disrupted sleep may lead to social withdrawal. Increasing evidence also suggests that social isolation may result in physical decline, but loss of physical function also may be socially isolating. Given the potential negative impacts of poor sleep, social isolation and physical decline on the health of older adults, longitudinal studies using objective, physiologic data are needed to understand the relationships between these variables. Unfortunately, it is difficult and expensive to characterize these variables in longitudinal clinical studies. Preclinical translational studies enable comprehensive phenotyping repeatedly across the life course. This application addresses important gaps in knowledge by investigating the relationships between social isolation, sleep quality, and physical function (i.e., gait speed, strength, activity) in a prospective longitudinal study of 25 vervets (Chlorocebus aethiops sabaeus) which range in age from middle-age to end of life. These nonhuman primates (NHPs) recapitulate many aging-related neurocognitive and physical declines and, unlike rodents, exhibit sleep/wake patterns that closely resemble those of humans. In addition to measures of physical function, we will develop a NHP Frailty Index based on the Fried Model of Frailty (i.e., weight loss, muscle strength, physical activity, and gait speed). We will accomplish our goals by leveraging a currently available dataset (one-time measures of sleep and social integration, plus annual physical function and frailty measurements), and add new longitudinal measurements of sleep, social integration, and physical performance to allow assessment of change with aging. Overall, we hypothesize that decline in any one of these domains may result in decrements in the other two domains which ultimately results in loss of the ability for independent living. The primary goals of this project is to establish the feasibility of a longitudinal study to determine the nature of the relationships between poor sleep, social isolation, and physical function, and generate key data necessary to support extramural grant applications to understand the biological mechanisms linking poor sleep to social and physical impairment. Characterization of these relationships will identify targets for intervention to prolong health span and independent living into advanced age. Overall, we have successfully recorded ECG, 24-hour activity, metrics of NHP frailty, and social behavior using the proposed in this application. We were unable to determine sleep stages using the proposed methodology. Data organization and analyses are ongoing. We successfully recorded ECGs and 24 hour heart rates in N=20 female vervet monkeys (9-29 years of age). In addition to measures of heart rates, measured as successive inter beat intervals (R-R intervals), we have collaborated with Dr. Hossam Shaltout (Obstetrics and Gynecology, Wake Forest School of Medicine) to determine several measures of heart-rate variability (HRV) including: (1) the standard deviation of successive IBIs (SDNN), (2) the root-mean square of successive differences (RMSSD), (3) very low frequency (VLF) power, (4) low frequency (LF) power, (5) high frequency (HF) power, and (6) the LF/HF ratio. We are currently determining to what degree age is associated with changes in HRV in the aging vervet monkey. These data are relevant to the goals of the WF Pepper OAIC PESC, as impaired cardiac autonomic control (indicated by HRV) may predict cardiovascular risk, frailty, and all-cause mortality in aging human populations. Activity levels were recorded continuously for 24-hour bouts in the same N=20 animals. These measures will contribute to our construction of a NHP index of frailty (see below). We have also measured normal gait speed in the population. Development of a NHP Frailty Index: We have successfully collected most of the data necessary to develop a NHP index of frailty, including (1) time spent hanging from the sides of the chain link enclosure with all four feet off the ground (measure of weakness), (2) gait speed, and (3) 24-hour activity levels. We are in the process of conducting bi-annual assessments of weight to determine patterns in unintentional weight loss. We are now poised to generate the frailty index and subsequently test the index's utility in predicting morbidity and mortality. Specifically, morbidity will be based on clinical diagnoses gathered from the NHP electronic medical records (EMR) in CARS (Computerized Animal Record System), and mortality will be characterized as animals becoming sick or reach end of life over the next months and years. Social Behavior: We have successfully collected data of social integration for the aging vervet cohort. Analyses are ongoing to determine the relationship between age and social isolation. Moreover, we are in the process of analyzing data to determine whether social integration predicts declines in physical function or vice versa. Additionally, given that several of aging vervets have reached their end of natural life (N=), our comprehensive, integrative approach will enable us to determine the utility of the experimental variables in predicting all-causes mortality. We have yet to accurately determined sleep stages - awake, rapid-eye-movement sleep (REM), and non-REM) in the NHPs using our proposed analytic approach (machine learning from combined actigraphy and heart rate telemetry). Thus, our determination of sleep is limited to distinguishing wakefulness from resting via actigraphy alone.
 
6. Project Title: PESC.2020.3 Real-world monitoring of limb loading for bone preservation during weight loss
  Leader: Ashley Weaver, PhD, Katherine Hsieh, PhD (Biomedical Engineering)
  Obesity is a serious health concern among older adults that is associated with a loss of physical function and increased disability. Despite known medical complications that accompany obesity, there is reluctance to recommend intentional weight loss for older adults. This hesitation is partly due to reduced bone mineral density (BMD) that is observed with weight loss in this population, which can exacerbate the potential for development of osteoporosis and osteoporotic fracture. Reduced BMD because of weight loss is thought to occur due to less mechanical stress on the bone with reduced body weight. Although resistance training increases mechanical loading and attenuates BMD loss, compliance is challenging among older adults. A novel method to increase mechanical loading and improve BMD is through wearing weighted vests. This mode of increasing external load is currently being evaluated in an active OAIC-investigator led clinical trial (INVEST). However, the INVEST trial does not contain a direct measure of limb loading. The lack of direct limb loading metrics combined with uncertainty as to which loading metrics are associated with improved bone health likely contributes to observed variation in individual levels of preserved BMD with external loading interventions. Therefore, the overarching goal of this study is to evaluate the feasibility of using innovative force-sensing insoles to compare limb-loading response between external loading during intentional weight loss and intentional weight loss alone. Force-sensing insoles are a portable, valid, and reliable wearable technology that measures force at the foot-shoe interface and provides an indicator of overall limb loading. These insoles can be used outside of a research or clinical setting and measures real-world activities for continuous hours. Leveraging the investigator’s ongoing clinical trial, the primary goal of this study is to evaluate the feasibility of measuring daily limb loading using force-sensing insoles in 45 overweight or obese older adults (ages 60-85 years) in an intentional weight loss program combined with weighted vest use (VEST+WL) or resistance training (RT+WL) compared to intentional weight loss alone (WL). We hypothesize we will be able to recruit participants into the study with high adherence and satisfaction when wearing the insoles. We will also compare a) daily loading metrics with the insoles and b) femoral stress and strain between groups using CT imaging and finite element (FE) modeling. Last, we will identify associations and between limb loading metrics, changes in physical function and BMD change. The results of this study will expand the ability for remote home-based assessment and intervention delivery through force-sensing insoles, a necessity during the COVID-19 pandemic. Moreover, these findings will understand how to tailor external loading during weight loss for older adults to maximize their physical function and prevent disability associated with aging. Recent Updates: 38 participants have completed baseline insole assessment: 26 of those have been randomized, 15 participants have competed at-home wear, and 5 have completed follow up assessment. Limb loading metrics (cumulative loading, loading rate, peak loading) are being processed and analyzed as data collection is on-going. Subject specific FE models of the dominant leg for all randomized subjects (n=26) have been generated. Work is underway to determine how insole loading correlates to loading at the mid-femur to define a translation value for appropriate application of the insole forces to the isolated femoral FE model. This test will be performed with a well-validated full human body FE model in loading phase, midstance, and terminal stance.
 
7. Project Title: PESC.2020.4 (Ignition Pilot) MicroRNAs biomarkers and miRNA-gene networks associated with exercise-modulated weight loss
  Leader: Genesio Karere, PhD (Internal Medicine)
  The prevalence of overweight and obesity is increasing in the US and the world-wide. Obesity is associated with comorbidities, including cardiovascular disease, diabetes and hypertension. Exercise is a proven approach to weight loss and is accompanied by physiological changes in skeletal muscles. Identification of skeletal muscle miRNAs associated with weight loss and measured in circulating biofluids is important for elucidating molecular indicators of weight loss and exercise-modulated molecular mechanisms underlying the weight loss. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that results in alteration of mRNA and protein abundance, impacting diverse biological processes including cell growth, proliferation, differentiation and apoptosis. These processes are fundamental to maintenance of tissue cellular homeostasis. miRNAs expression is responsive to external stimuli, including exercise. Consequently, miRNAs are emerging potential biomarkers because are readily dateable in biofluids, including plasma/serum, saliva and urine, and potential therapeutic targets. Dysregulation of a few specific miRNAs (miR375. 126-3p, 663, 30c-p, 100-5, 27-3p, and 590-5p) has been implicated in weight loss after bariatric surgery (Doyon L et al. 2020). Inhibition of miR-324-5p resulted in reduction of adipose tissue and overall body weight loss in juvenile mice (Li D et al 2019). Other studies have revealed miRNAs dysregulated after exercise. For example, the expression of skeletal muscle-specific miRNAs (miR-1, miR-133a and b, miR-208b and miR-206) measured in plasma increased after chronic exercise (Banzet et al. 2013). In another study, serum circulating levels of miR-486 decreased after chronic versus acute exercise, and the expression was negatively correlated with VO2 max (Aoi et al. 2013). Together these studies separately suggest that miRNAs are responsive to weight loss and exercise. However, a comprehensive study revealing miRNA biomarkers of and molecular mechanisms underlying weight loss due to exercise is lacking. The objective of the proposed pilot study is to evaluate the feasibility of using miRNAs to predict weight loss after exercise and to provide potential mechanistic insights. We hypothesize that miRNAs are potential biomarkers predicative of weight loss after exercise, providing potential insights to molecular mechanisms underlying exercise outcomes.

We will test the hypothesis using the following specific aims:

1. Identify circulating miRNAs in plasma that correlate with weight loss after exercise. We will use small RNA Seq to assess miRNAs in plasma at baseline and post intervention in two groups: a group that showed weight loss after exercise (n= 5 pairs) and another group that exhibited no change (n= 5 pairs). Outcomes will be identification of miRNAs differentially expressed between baseline and post interventions in each group and miRNAs that are differentially expressed between the groups post intervention.

2. Identify skeletal muscle miRNA-gene regulatory networks associated with weight loss. We use the same study design in Aim 1 and small RNA Seq to identify differentially expressed miRNAs. In addition, we will identify miRNA-gene regulatory networks by integrating miRNA data and existing skeletal muscle transcriptomic data from the same individuals. Outcomes will be identification of skeletal muscle differentially expressed miRNAs and miRNA-gene networks dysregulated in exercise-modulated weight loss, providing potential biomarkers and insights to molecular mechanisms underlying weight loss after exercise.
 
8. Project Title: PESC.2021.1 Epigenetics of an intensive lifestyle intervention: the Look AHEAD study.
  Leader: Lindsay Reynolds, PhD (Epidemiology and Prevention), Mark Espeland, PhD (Gerontology and Geriatric Medicine), Timothy Howard, PhD (Biochemistry), Carl Langefeld, PhD (Biostatistics)
  Diabetes and obesity increase the risk of age-related health deficits and may accelerate epigenetic aging. Lifestyle interventions promoting weight loss, such as the Action for Health in Diabetes (Look AHEAD) trial intervention, can potentially buffer against decline in age-related health status in overweight or obese adults with type 2 diabetes. However, significant variation exists among who benefits from intensive lifestyle intervention (ILI) programs. Better understanding of the biological impact of ILI could help lay the foundation for personalized medicine approaches to predict individual responses to ILI. Epigenetic aging measures (the difference between a DNA methylation-based measure of biological age vs. chronological age) capture aspects of biological aging, and have potential as biomarkers of impact of ILI. We hypothesize that an ILI is more beneficial for participants with higher baseline measures of epigenetic aging, and that changes in epigenetic aging mediate benefits of ILI on accumulation of health deficits over time. To test our hypothesis, we are proposing to test epigenetic aging measures as predictors and biomarkers of the impact of the Look AHEAD ILI in adults with diabetes and obesity. We will assess baseline epigenetic age acceleration as a predictor of impact of an ILI on frailty in adults with diabetes and obesity. The goal of this pilot study is to generate preliminary data establishing feasibility and estimates for sample size calculations for an R01 application. We will generate epigenomic data and DNA methylation-based estimates of epigenetic aging in samples from a subset (n=32) of participants of the Look AHEAD trial at baseline and ~16 years after baseline. We will generate descriptive statistics for baseline epigenetic aging measures (epigenetic age acceleration and rate of aging) and for the change in epigenetic aging measures from baseline to Year 16 visit. Baseline epigenetic aging and change in epigenetic aging from baseline to Year 16 visit will be compared between intervention arms: ILI (n=16) vs. diabetes support and education (control condition; n=16). We will also compute associations of baseline epigenetic aging measures with change in frailty index from baseline to Year 16 visit (n=32). Our experienced and multi-disciplinary team, led by an Early Career Investigator, is well-positioned to perform the proposed pilot study, and future studies aiming to better understand the biological basis of benefit of an intensive lifestyle intervention for aging adults with diabetes who are overweight or obese.
 
DEVELOPMENT PROJECTS (2 Development Projects Listed)
1. Project Title: Development of Automated Approaches to Obtaining Age-Related Body Composition Phenotypes from Routine Computed Tomography (CT) Examinations
  Leader: Leon Lenchik, MD
  Core(s): Pilot and Exploratory Studies Core (PESC)
BioImaging (BioImaging)
  This project aims to develop automated approaches to CT segmentation of muscle using machine learning methods. The long-term objective is to create a widely available, automated image analysis algorithm, which will extract measures of body composition and structure from clinical image repositories in data warehouses and hospital-based image archive systems. These analyses could identify predictors of age-related decline in physical performance across multiple hospital health-care delivery systems. This project resulted in a successful R21 application, (funding to begin in 7/21) This study received ancillary funding to support acquiring CTs in the SOMMA study so this automation can be incorporated into the analyses of these scans. This project has led to 2 peer-reviewed publications and an R21 application to MrOS, Novel Computed Tomography (CT) Imaging Biomarkers in Older Men for Predicting Adverse Geriatric Health Outcomes.
 
2. Project Title: Novel Big Data Processing Algorithms and Summary Metrics to Enhance our Understanding of Health and Mobility (PepperMINT)
  Leader: Michael E Miller, PhD; W. Jack Rejeski, PhD, Jason Fanning, PhD, Shyh-Huei Chen, PhD
  Core(s): Clinical Research Core (CRC)
Biostatistical Design and Analysis Core (BIC)
  An important step in advancing accelerometry lies in first cross-calibrate core monitoring devices using direct observation in order to leverage data produced in existing datasets derived from large multisite trials (e.g., Look AHEAD; LIFE). Once complete, these data can be used to generate sophisticated metrics that better capture both amount and variability in sedentary and physical activity behaviors. Eligible participants will be older adults (aged = 65) who are overweight or obese (BMI=30-45 kg/m2), and low-active (i.e., engaging in less than 2 days/wk of structured physical activity for at least 20 minutes). We will aim to recruit an even number of males and females (i.e., 15 each) and within each sex, we will aim to recruit at least 7 individuals with a short physical performance battery (SPPB) score >9, and at least 7 with an SPPB score = 9. Excluded individuals will be unable to walk without assistive devices or will have cognitive impairment as indicated by a Montreal Cognitive Assessment score of less than 22. This study consists of two phases. During the first phase, a sample of low-active older adults (N = 30) will be guided through a series of 13 tasks while wearing two Actigraph accelerometers, one ActivPAL, one Fitbit, and one RT3. The main purpose of this phase is to identify how each monitor captures movement at low, moderate, and vigorous intensities, sitting and lying still, and transitioning for sitting to standing. Additional activities of daily living (e.g., folding laundry, sweeping) will be included to assess the potential influence of these tasks on the accelerometer data. Participants will spend one week wearing the monitors, and then return to repeat the task list. Following completion of this period, the analytic team (Miller, Chen) will utilize the data to identify effective means of devices calibration using metrics such as cadence (steps/minute) or energy expenditure (MET/h). This study has completed and data analysis is underway.
 
RESEARCH (8 Projects Listed)
1. Project Title: SENESCENT CELL BURDEN IN HUMAN AGING AND OBESITY: FUNCTIONAL CONSEQUENCES AND REDUCTION BY CALORIC RESTRICTION
  Leader(s): JUSTICE, JAMIE NICOLE
    WAKE FOREST UNIVERSITY HEALTH SCIENCES
    NIH K01AG059837 / ( 2018 - 2023 )
  Core(s): - Pilot and Exploratory Studies Core (PESC)
  Project SummaryA key aim of this proposal is to equip the candidate, Dr. Jamie Justice, with the expertise to become anindependent investigator who can advance interventions that extend healthy lifespan to randomized, controlledtrials in older persons. Specifically, cellular senescence is a biologic hallmark of aging that emerging preclinicalevidence indicates could have profound consequences on aging-related disease and function, and removal ofsenescent cells results in robust improvements in healthspan in rodents. Translation of these interventions toclinical trial has been proposed, yet health consequences of cell senescence and therapeutic potential has notbeen evaluated in humans. Dr. Justice's preliminary data in a small number of older women are the first toshow that cells expressing tumor suppressor protein and senescence biomarker p16INK4a are present inadipose tissue from older adults and related to worse physical function, but exercise and weight loss by caloricrestriction may mitigate this burden. The proposed research project represents a critical next step byexamining the effects of caloric restriction (CR) on cell senescence in a prospective randomized controlled trial(RCT). The primary hypothesis is that a CR intervention will reduce senescent cell burden and this reductionwill be related to improvement in functional and metabolic outcomes. This will be accomplished by capitalizingon a recent NIH-funded RCT (VEGGIE, R01DK103531) and the candidate's engaged inter-disciplinaryprimary mentoring team (Drs. Nicklas, Ding, Kritchevsky, Kirkland). VEGGIE will determine the effects of CRdesigned to achieve 10% weight loss vs. health education control in 200 men and women aged 40-65 yearswith obesity (BMI 30-45 kg/m2), to characterize epigenetic and transcriptomic effects of CR in adipocytes andperipheral blood monocytes and T cells, and associations with physical and metabolic function. We propose anancillary investigation in a subset of 90 participants (50-65 years, n=45 per grp) to determine the effects ofCR on senescent cell burden (Aim 1): a) proportion of p16INK4a expressing senescent cells(immunohistochemistry) in subcutaneous abdominal adipose tissue; b) expression of senescence biomarkersin isolated adipocytes and monocytes (RNAseq) and T cells (p16INK4a expression); and c) SASP biomarkers inplasma (cytokine/chemokine panel). We will also examine cross-sectional associations of age and obesity withcell senescence (Aim 2), and relationships between changes in senescence biomarkers and physical functionand metabolic outcomes (Aim 3). The research proposed is aligned with an approved NIA concept todevelop markers of aging-related biologic mechanisms for human studies. Additionally, it will provide essentialtraining for the candidate, who will establish expertise in cell senescence and translational research, anddevelop competencies in leading clinical trials with biological outcomes. This approach provides the idealplatform to advance the candidate's career as an independent investigator, and provide the foundation toestablish the role of cell senescence in human age-related functional decline.
 
2. Project Title: IDENTIFYING FRAILTY IN PRIMARY CARE: IMPLEMENTATION OF AN ELECTRONIC MEDICAL RECORD-BASED FRAILTY INDEX
  Leader(s): CALLAHAN, KATHRYN
    WAKE FOREST UNIVERSITY HEALTH SCIENCES
    NIH K76AG059986 / ( 2018 - 2023 )
  Core(s): - Clinical Research Core (CRC)
  Project SummaryThis Beeson award seeks to equip the candidate, Dr. Kathryn E. Callahan, with the expertise to become anindependent investigator to advance use of aging-related metrics and interventions to promote health, function,and quality of life in frail and at-risk older adults. Frailty is prevalent among older adults, and associated withnegative outcomes, including hospitalizations, mobility disability, admission to skilled nursing facilities, andmortality. Despite efforts to define and quantify frailty, time and resource constraints limit the feasibility of frailtymeasures in clinical practice. Dr. Callahan's preliminary work supports the feasibility of translating anEMR-based Frailty Index, or eFI into the Wake Forest Baptist Health (WFBH) EMR, and demonstrates an initialassociation between eFI score and hospitalizations and mortality. The proposed research project representscritical next steps: (1) to adapt and refine the eFI using ambulatory care data, (2) assess its predictive value forhealthcare outcomes for older adults, and (3) conduct a pilot of implementation in Medicare Shared SavingsProgram/Next Generation Accountable Care Organization primary care practices, to collect critical dataregarding feasibility, acceptability, and effectiveness. The scientific goal is to develop and implement an indexto define a population of frail older adults who would benefit from personalized evidence-based interventions.This work is essential to inform larger-scale implementation trials of interventions to mediate negative andcostly health outcomes for frail older adults. We hypothesize that self-report and functional data from AnnualWellness Visits (AWVs) in the EMR will further refine the predictive value of the eFI; and that implementation ofthe eFI will be feasible and acceptable. This project is supported by engaged mentors (Drs. Williamson andBoustani) and a highly interactive, inter-disciplinary advisory committee (Drs. Foley, Rejeski, and Pajewski)whose expertise and complementary skills are a noteworthy asset to this project. We propose the adaptationand refinement of the eFI within the WFBH EMR, using data from older adults enrolled in the WFBH MSSP/Next Gen ACO (Aim 1): we will integrate AWV data, and refine the predictive value of eFI scores in thispopulation. We will then conduct a pilot study implementing the adapted eFI score in six MSSP/Next Gen ACOprimary care practices, and follow health outcomes. The research proposed aligns with an NIA priority toimprove the health, well-being, and independence of adults as they age. It will also provide essential trainingfor the candidate, who will establish expertise in implementation science, achieve fluency in clinical informatics,and develop competencies in leading implementation trials. This approach provides the ideal platform toadvance the candidate's career as an independent investigator and provides the foundation to establish frailtymetrics in practice, leveraging the learning health system to implement interventions to improve health andfunction.
 
3. Project Title: BRAIN NETWORKS AND MOBILITY FUNCTION: B-NET
  Leader(s): KRITCHEVSKY, STEPHEN B.; LAURIENTI, PAUL ;
    WAKE FOREST UNIVERSITY HEALTH SCIENCES
    NIH R01AG052419 / ( 2017 - 2022 )
  Core(s): - Leadership and Administrative Core (LAC)
- Clinical Research Core (CRC)
- BioImaging (BioImaging)
- Biostatistical Design and Analysis Core (BIC)
  Project Summary/AbstractDeclining mobility function is a common age-related phenomenon that is associated with reduced quality of lifeand high societal costs. Recently, the brain's critical role in mobility function has been recognized usingimaging approaches assessing white matter characteristics. A new paradigm considering the brain as acomplex network uses MRI to directly characterize the brain as a functional network. Brain Networks andMobility Function: B-NET brings together national leaders in brain network science, neurology and mobilityassessment to apply this innovative network paradigm to elucidate the aging brain's role in declining mobility.We propose that functional connectivity within and between the sensorimotor cortex -- community structure(SMC-CS) -- predicts declining mobility; and that SMC-CS will be associated with mobility independent ofknown relationships between white matter integrity and mobility function.B-Net will establish a cohort of 240 community-dwelling older adults (age range 70-85) and measure mobilityfunction at baseline, 6, 18 and 30 months using the extended short physical performance battery (eSPPB). TheMRI will be repeated at 30 months. B-Net's specific aims are to:Specific Aim 1. Determine the baseline association between SMC-CS and eSPPB score. We hypothesizethat SMC-CS will be associated with eSPPB performance independent of known correlates of mobility functionand white matter integrity (i.e. fractional anisotropy and white matter lesions).Specific Aim 2. Determine whether baseline SMC-CS predicts mobility decline. We hypothesize that poorerbaseline SMC-CS will be predict declining eSPPB scores after accounting for known correlates of mobilityimpairment including white matter integrity, cardiovascular fitness, and muscle strength.Specific Aim 3. Repeat brain MRI imaging to determine the longitudinal association between changes inSMC-CS and changes in eSPPB score. We hypothesize that longitudinal declines in SMC-CS will besignificantly associated with declining eSPPB performance independent of known correlates of lower extremityfunction decline and white matter integrity.B-NET tests a novel emerging paradigm regarding the CNS's role in age-related functional decline to supportthe development of innovative strategies to sustain mobility function in older adults, a critical public healthneed.
 
4. Project Title: LONG-TERM FUNCTION AND HEALTH EFFECTS OF INTENTIONAL WEIGHT LOSS IN OBESE ELDERS
  Leader(s): HOUSTON, DENISE KATHRYN
    WAKE FOREST UNIVERSITY HEALTH SCIENCES
    NIH R01AG056418 / ( 2017 - 2022 )
  Core(s): - Clinical Research Core (CRC)
- BioImaging (BioImaging)
- Biostatistical Design and Analysis Core (BIC)
- Integrative Biology Core (Integrative Biology Core)
  Project Summary/AbstractObesity exacerbates age-related declines in function, is a strong determinant of mobility disability, and isassociated with poorer clinical outcomes and quality of life. Given that over one-third of older adults are obeseand the public health burden of age-related disability, identifying effective therapies that prevent obesity-relateddeclines in function and health in older adults are urgently needed. Clinical trials by our group and others showthat diet-induced weight loss interventions, particularly when combined with exercise, improve bodycomposition and physical and metabolic function over the short-term (in the weight-reduced state) in obeseolder adults. However, the overall safety and long-term benefits of intentional weight loss in this populationremain controversial and weight loss is often not recommended because of uncertainty of whether the benefitsoutweigh the risks (e.g., loss of muscle mass and bone). Furthermore, most individuals are not successful atlong-term maintenance of weight loss. Thus, whether improvements in physical and metabolic function andother health parameters persist over time among older adults following intentional weight loss, particularly ifweight regain occurs, is unknown. The overall goals of the proposed study are to determine if the short-termbenefits of intentional weight loss on physical and metabolic function are sustained and to examine potentiallong-term benefits and risks of weight loss in older adults. We will determine the effects of randomization todiet-induced weight loss on physical function (primary outcome), body composition, bone mineral density, andcardiovascular risk factors (secondary aims) a minimum of 3 and a maximum of 10 years after interventioncompletion. Our general hypothesis is that randomization to weight loss will result in improved long-termphysical and metabolic function compared to randomization to no weight loss. We will take advantage of ourunique access to five NIH-supported randomized, controlled trials that enrolled overweight or obese (BMI=27kg/m2) older adults (mean age at randomization, 67.3 years) and randomized them to weight loss plus exercise(n=458) or exercise alone (n=396) at Wake Forest from 2005 to 2014, the pooling of which will providesufficient sample size to definitively evaluate the long-term functional and health consequences of priorintentional weight loss. We will also explore the long-term effects of randomization to weight loss on quality oflife (SF-36), obesity- and weight loss-related medical events (e.g., knee replacements, fractures, MI),hospitalizations, and mortality; and assess the role of current behaviors (e.g., dietary intake, physical activity)on weight loss maintenance, physical function, body composition, and cardiovascular risk factors. Theproposed study will be the first randomized, controlled design to examine the long-term effects of intentionalweight loss in older adults and builds on our Aging Center's collaborative research focus in geriatric obesitytreatment to answer compelling and clinically important questions regarding the long-term efficacy and safetyof weight loss interventions in older adults in an efficient and cost-effective manner.
 
5. Project Title: INCORPORATING NUTRITION, VESTS, EDUCATION, AND STRENGTH TRAINING IN BONE HEALTH (INVEST IN BONE HEALTH)
  Leader(s): BEAVERS, KRISTEN MARIE
    WAKE FOREST UNIVERSITY
    NIH R01AG059186 / ( 2019 - 2024 )
  Core(s): - Pilot and Exploratory Studies Core (PESC)
- Clinical Research Core (CRC)
- BioImaging (BioImaging)
  PROJECT SUMMARYOld age and obesity are prevalent risk factors for morbidity and mortality. Weight loss (WL) ameliorates manyclinical consequences of obesity; yet despite its benefits, recommendation of intentional WL in older adultsremains controversial. Reluctance stems, at least in part, from loss of bone mass known to accompany overallWL and the potential for exacerbation of age-related risk of osteoporosis and fracture. Addition of resistanceexercise training (RT) to WL is an effective means to attenuate, but not stop, WL-associated reductions in bonemineral density (BMD); however, conventional RT interventions present barriers to long term feasibility (i.e.,expensive equipment, on-site participation, safety supervision by trained staff, and waning compliance).Alternately, treating the WL-associated decrease in mechanical stress by replacing lost weight externally mayalso preserve bone mass. Pilot data from our institution signal that weighted vest use (designed to mimicweight stability) during WL is both feasible and likely efficacious in reducing WL-associated hip BMD loss whileincreasing biomarkers of bone formation. If confirmed, the greater availability, ease of administration, andreduced cost of weighted vest use to offset WL-associated bone loss, as compared to RT, holds significantpublic health potential as a translatable strategy to maximize the cardiometabolic benefits of WL, whileminimizing negative implications for the musculoskeletal system. The main goal of the proposed R01 study isto compare the effects of WL alone and with weighted vest use or RT on several indicators of bone health andsubsequent fracture risk. We propose a 12 month trial in 192 older (65-79 years) adults with obesity (BMI=30-40 kg/m2) randomized to one of three interventions (n=64/group): WL alone (WL; caloric restriction targeting10% WL and following national obesity treatment guidelines); WL plus weighted vest use (WL+VEST; =6hours/day, weight replacement titrated up to 10% WL); or, WL plus structured RT (WL+RT; 3 days/week, 10exercises, 10-12 repetitions). Our primary study outcome is 12 month change in total hip trabecular volumetricBMD (vBMD) and we hypothesize that despite similar reductions in total body weight: (1) participants in theWL+VEST group will show attenuated losses of total hip trabecular vBMD versus WL, and (2) loss in total hiptrabecular vBMD will be no greater in WL+VEST compared to WL+RT. Led by a talented New Investigator, thisproposal is a natural extension of the work accomplished during the PI s current MRSDA (K01 AG047291), andconfers public health impact by testing a translatable strategy aimed at optimizing intentional WL in older adultswith obesity while elucidating mechanisms governing musculoskeletal response to WL.
 
6. Project Title: STUDY OF MUSCLE, MOBILITY AND AGING (SOMMA)
  Leader(s): CUMMINGS, STEVEN RON; HEPPLE, RUSSELL T ; KRITCHEVSKY, STEPHEN B. ; NEWMAN, ANNE B. ;
    CALIFORNIA PACIFIC MED CTR RES INSTITUTE
    NIH R01AG059416 / ( 2018 - 2023 )
  Core(s): - Clinical Research Core (CRC)
- BioImaging (BioImaging)
- Integrative Biology Core (Integrative Biology Core)
  Mobility inevitably declines with age, more in some than other people, often leading to mobility disabilitywith dependency, decreased quality of life, and enormous health care costs. The role of age-related biologicalchanges in skeletal muscle on the decline in mobility is poorly understood. We hypothesize that muscle massand the capacity to produce ATP are strong determinants of the mobility disability in older adults. Based onadvances from laboratory studies of muscle aging, we also hypothesize that denervation, oxidative damage,and decreased autophagic flux interact and contribute to declines in fitness, endurance and an increased riskof mobility disability. We will also use transcriptomic profiling by RNAseq to discover patterns of geneexpression that play important roles in the loss of mobility with aging. In the Study of Muscle Mobility and Aging (SOMMA), a prospective, longitudinal study of men andwomen age 70 to 90, our team of experts in clinical and laboratory sciences will use innovative and state-of-the-art technologies with rigorous quality control to test these hypotheses and discover new pathways for theloss of mobility with aging. We will measure quadriceps contractile volume by MRI and total muscle mass byd3 creatine dilution. We will use 31PMRS to assess the capacity of the quadriceps to generate ATP (ATPmax).In tissue form, muscle biopsies quantify denervation and oxidative damage to contractile proteins. SOMMA willbe the first to quantify autophagic flux to assess the role of autophagy in the loss of mobility with aging. We userespirometry on fresh tissue to quantify the contribution of mitochondria to ATPmax and mobility disability.These properties interact: for example, decreased autophagic flux promotes the accumulation of oxidativedamage and denervation, and understanding these relationships will guide the analysis and interpretation ofour results. Furthermore, we will use unbiased RNA-sequencing (RNA-seq) to profile the entire transcriptometo discover new associations between clusters of genes and individual variation in rates of loss of fitness (peakVO2), muscle mass, and risk of mobility disability. Field centers at Wake Forest and Pittsburgh, with exceptional track records for recruiting and retainingolder adults in complex studies, will enroll 875 women and men age 70 89 with a gait speed = 1.0 m/s,providing sufficient power to identify important relationships between individual and combinations of propertiesand the risk of mobility disability. SOMMA may identify and prioritize targets for new therapeutics and tailored exercise regimens. Wealso will create a unique archive of tissue, blood, with longitudinal data about important clinical outcomes thatthe scientific community can use to efficiently test new hypotheses about muscle and loss of mobility withaging.
 
7. Project Title: Health Aging & Later-Life Outcomes Planning (HALLO-P)
  Leader(s): KRITCHEVSKY, STEPHEN B.; MILLER, MICHAEL E.; NICKLAS, BARBARA J; REJESKI, WALTER JOHN;
    WAKE FOREST UNIVERSITY HEALTH SCIENCES
    NIH U01AG073240 / ( 2021 - 2024 )
  Core(s): - Clinical Research Core (CRC)
- BioImaging (BioImaging)
- Biostatistical Design and Analysis Core (BIC)
- Integrative Biology Core (Integrative Biology Core)
  The Health, Aging and Later-Life Outcomes Planning Grant (HALLO-P) is submitted in response to RFA-AG-21-016. Collectively, HALLO-P affiliated investigators have led 17 clinical trials of caloric restriction (CR; 3 ongoing), enrolling 2,773 adults (ages 55-91) with BMIs = 27 kg/m2, showing multiple beneficial physiologic changes associated with lower disease and disability risk. Whether this translates to actual reductions in disease and disability is unclear. A large multi-year trial with definitive clinical outcomes is needed to fill this evidence gap. Time restricted feeding (TRF) could be an attractive alternative to CR if it produced similar health benefits, was more easily sustained, and mitigated CR s undesirable loss of muscle and bone. The overall goal of this 3-year HALLO planning grant is to develop a protocol for a rigorous, multi-site, randomized clinical trial (RCT) comparing clinically-relevant health outcomes in older persons randomized to daily CR, a TRF regimen, or a non-dietary attention control group employing innovative mHealth tools to promote adherence. We will complete a 12-month pilot study enrolling 120 older adults (age =60 years; 50% women; =23% minority) to provide critical information on feasibility, intervention delivery, and data informing effect size determination. HALLO-P s Objectives are to: 1. Establish a scientific advisory board and other structures to guide planning activities and the design of a full- scale RCT that engage a wide range of stakeholders and build a national constituency for the project. 2. Refine our mHealth behavior-change and adherence tracking platform the HALLO-P Companion App to optimize delivery of both the CR and TRF interventions. 3. Conduct focus groups and a 12-month pilot RCT of: 1) 20% CR delivered in-person; 2) 20% CR delivered remotely via video conferencing; and 3) TRF (8-10 hours) with ad libitum caloric intake. Pilot data will help refine recruitment criteria, estimate recruitment yields, and refine intervention approaches. We will use doubly- labeled water to measure achieved CR and continuous glucose monitoring to assess adherence to TRF. 4. Model aging biomarker changes for differing CR doses using WF OAIC repositories and the HALLO-P pilot. Existing epidemiological databases will be used to estimate the anticipated effect of these biomarker changes on clinical outcomes and to derive key design metrics related to inclusion/exclusion criteria, and event rates related to multi-morbidity, health deficit accumulation, and functional decline/disability; and 5. Integrate new data, the scientific literature .and expert advice to prepare a protocol, and develop informed consent forms, manuals of operation, study forms, and related systems to permit the rapid launch of the larger trial upon completion of the pilot activities in coordination with the other U01 project funded by this mechanism.
 
8. Project Title: PRAGMATIC EVALUATION OF EVENTS AND BENEFITS OF LIPID-LOWERING IN OLDER ADULTS (PREVENTABLE)
  Leader(s): ALEXANDER, KAREN P; AMBROSIUS, WALTER T ; HERNANDEZ, ADRIAN ; WILLIAMSON, JEFF DOUGLAS ;
    DUKE UNIVERSITY
    NIH U19AG065188 / ( 2019 - 2026 )
  Core(s): - Clinical Research Core (CRC)
  There is an urgent need for evidence to guide clinical care of older adults due to demographic shifts, includinglonger life expectancy and a recent doubling of the older adult population. Statins reduce recurrent CVD eventsand prevent initial events in patients younger than 75 years. However, clinical research has often excludedpersons older than 75 years due to a higher prevalence of comorbidity and frailty so little to no evidence isavailable to guide care in this population. For older adults living longer, the promise of preventing cognitiveimpairment is as compelling as preventing a CVD event, but some evidence suggests statins maycontribute to memory difficulty or muscle symptoms. There is equipoise regarding the usefulness of statinsfor primary CVD, dementia, and disability prevention in adults older than 75 years, especially in the settingof multiple chronic conditions, advanced age, or frailty. Evidence to improve cognitive and functionaloutcomes in older populations with diverse race/ethnicity and health status will require new clinical trialapproaches with sustainable methodology and infrastructure. We propose PREVENTABLE (PRagmaticEValuation of evENTs And Benefits of Lipid-lowering in oldEr adults), the first statin trial with a non-CVDprimary outcome survival free of dementia or persisting disability. Using a placebo-controlled pragmaticclinical trial (PCT) design across PCORnet and VA network, the trial will be under the leadership of Dr. KarenAlexander at DCRI, Dr. Jeff Williamson at WFSM, Dr. Adrian Hernandez at DCRI, and Dr. Walter Ambrosius atWFSM. This team has established experience and track-record of accomplishment in the design and conductof PCTs, trial expertise in ascertaining cognitive and disability outcomes in older adults, and is supported by arobust administrative infrastructure for coordinating these shared responsibilities for success. The overarchinggoal of PREVENTABLE is to generate knowledge about the role of statins in older adults, a population in whichrisk/benefit for primary prevention has been under studied. The hypothesis is that a large trial conducted in anolder adult population will demonstrate the benefit of statins for reducing dementia, disability, and CV events.We further hypothesize that extensive genomic, biochemical and imaging ancillary studies will offer uniqueinsights into these key outcomes. PREVENTABLE has the following specific aims: AIM 1: Determine the roleof a moderate-intensity statin in preventing dementia and prolonging disability-free survival in patients 75 yearsand older without clinically evident coronary heart disease, including those with frailty, impaired physicalfunction, mild cognitive impairment, polypharmacy, and multi-morbidity. AIM 2: Determine the role of moderate-intensity statin in preventing hospitalization for myocardial infarction/acute coronary syndrome, stroke, heartfailure, revascularization or cardiovascular-related death, and preventing either mild cognitive impairment ordementia. AIM 3: Test the safety and tolerability of statins in older adults and collect 17,000 bio-specimens toadvance precision health.
 
PUBLICATIONS
2022
  1. Designing Actionable Solutions and Curriculum for Pain Disparities Education.
    Adams MCB, Denizard-Thompson NM, DiGiacobbe G, Williams BL, Brooks AK
    Pain Med, 2022 Feb 1, 23(2): 288-294
    https://doi.org/10.1093/pm/pnab289 | PMID: 34601612 | PMCID: PMC9020483
    Citations: | AltScore: 12.15
  2. Longitudinal relationship of baseline functional brain networks with intentional weight loss in older adults.
    Burdette JH, Bahrami M, Laurienti PJ, Simpson SL, Nicklas BJ, Fanning J, Rejeski WJ
    Obesity (Silver Spring), 2022 Apr, 30(4): 902-910
    https://doi.org/10.1002/oby.23396 | PMID: 35333443 | PMCID: PMC8969753
    Citations: | AltScore: 163.08
  3. Economic Outcomes of Rehabilitation Therapy in Older Patients With Acute Heart Failure in the REHAB-HF Trial: A Secondary Analysis of a Randomized Clinical Trial.
    Chew DS, Li Y, Zeitouni M, Whellan DJ, Kitzman D, Mentz RJ, Duncan P, Pastva AM, Reeves GR, Nelson MB, Chen H, Reed SD
    JAMA Cardiol, 2022 Feb 1, 7(2): 140-148
    https://doi.org/10.1001/jamacardio.2021.4836 | PMID: 34817542 | PMCID: PMC8613698
    Citations: 1 | AltScore: 26.6
  4. Intervening on exercise and daylong movement for weight loss maintenance in older adults: A randomized, clinical trial.
    Fanning J, Rejeski WJ, Leng I, Barnett C, Lovato JF, Lyles MF, Nicklas BJ
    Obesity (Silver Spring), 2022 Jan, 30(1): 85-95
    https://doi.org/10.1002/oby.23318 | PMID: 34932885 | PMCID: PMC8711609
    Citations: | AltScore: 149.55
  5. Evaluation of a blood-based geroscience biomarker index in a randomized trial of caloric restriction and exercise in older adults with heart failure with preserved ejection fraction.
    Justice JN, Pajewski NM, Espeland MA, Brubaker P, Houston DK, Marcovina S, Nicklas BJ, Kritchevsky SB, Kitzman DW
    Geroscience, 2022 Jan 10, 44(2): 983-995
    https://doi.org/10.1007/s11357-021-00509-9 | PMID: 35013909 | PMCID: PMC9135899
    Citations: | AltScore: 0.5
  6. Tailoring a physical activity intervention to older adults receiving intensive chemotherapy for acute myeloid leukemia (AML): One size does not fit all.
    Klepin HD, Tooze JA, Rejeski J, Mihalko S, Pardee TS, Demark-Wahnefried W, Powell BL, Geiger AM, Kritchevsky S
    J Geriatr Oncol, 2022 May, 13(4): 511-515
    https://doi.org/10.1016/j.jgo.2021.11.017 | PMID: 35487616 | PMCID: PMC9060358
    Citations: | AltScore: 12.85
  7. Physical Rehabilitation in Older Patients Hospitalized with Acute Heart Failure and Diabetes: Insights from REHAB-HF.
    Murray EM, Whellan DJ, Chen H, Bertoni AG, Duncan P, Pastva AM, Kitzman DW, Mentz RJ
    Am J Med, 2022 Jan, 135(1): 82-90
    https://doi.org/10.1016/j.amjmed.2021.08.001 | PMID: 34516959 | PMCID: PMC8688185
    Citations: | AltScore: 4.35
  8. Geriatric assessment for older adults receiving less-intensive therapy for acute myeloid leukemia: report of CALGB 361101.
    Ritchie EK, Klepin HD, Storrick E, Major B, Le-Rademacher J, Wadleigh M, Walker A, Larson RA, Roboz GJ
    Blood Adv, 2022 Jun 28, 6(12): 3812-3820
    https://doi.org/10.1182/bloodadvances.2021006872 | PMID: 35420672
    Citations: | AltScore: 4.35
  9. Psychosocial stress increases risk for type 2 diabetes in female cynomolgus macaques consuming a western diet.
    Silverstein-Metzler MG, Frye BM, Justice JN, Clarkson TB, Appt SE, Jeffrey Carr J, Register TC, Albu-Shamah M, Shaltout HA, Shively CA
    Psychoneuroendocrinology, 2022 May, 139: 105706
    https://doi.org/10.1016/j.psyneuen.2022.105706 | PMID: 35259592 | PMCID: PMC8977247
    Citations: | AltScore: 8.1
  10. Predicting Future Mobility Limitation in Older Adults: A Machine Learning Analysis of Health ABC Study Data.
    Speiser JL, Callahan KE, Ip EH, Miller ME, Tooze JA, Kritchevsky SB, Houston DK
    J Gerontol A Biol Sci Med Sci, 2022 May 5, 77(5): 1072-1078
    https://doi.org/10.1093/gerona/glab269 | PMID: 34529794 | PMCID: PMC9071470
    Citations: | AltScore: 2.5
  11. The geriatrics research instrument library: A resource for guiding instrument selection for researchers studying older adults with multiple chronic conditions.
    Tisminetzky M, Delude C, Allore HG, Anzuoni K, Bloomstone S, Charpentier P, Hepler JP, Kitzman DW, McAvay GJ, Miller M, Pajewski NM, Gurwitz J
    J Multimorb Comorb, 2022, 12: 26335565221081200
    https://doi.org/10.1177/26335565221081200 | PMID: 35586036 | PMCID: PMC9106318
    Citations: | AltScore: 2
  12. Older Patients With Acute Decompensated Heart Failure Who Live Alone: An Analysis From the REHAB-HF Trial.
    Warraich HJ, Kitzman DW, Nelson MB, Mentz RJ, Rosenberg PB, Lev Y, Whellan DJ
    J Card Fail, 2022 Jan, 28(1): 161-163
    https://doi.org/10.1016/j.cardfail.2021.06.005 | PMID: 34147611 | PMCID: PMC8734952
    Citations: | AltScore: 5.1
 
2021
  1. Relationship of physical function with quality of life in older patients with acute heart failure.
    Aladin AI, Whellan D, Mentz RJ, Pastva AM, Nelson MB, Brubaker P, Duncan P, Reeves G, Rosenberg P, Kitzman DW
    J Am Geriatr Soc, 2021 Apr 10, 69(7): 1836-1845
    https://doi.org/10.1111/jgs.17156 | PMID: 33837953 | PMCID: PMC8273137
    Citations: 1 | AltScore: 8.7
  2. Brain region-specific disruption of mitochondrial bioenergetics in cynomolgus macaques fed a Western versus a Mediterranean diet.
    Amick KA, Mahapatra G, Bergstrom J, Gao Z, Craft S, Register TC, Shively CA, Molina AJA
    Am J Physiol Endocrinol Metab, 2021 Nov 1, 321(5): E652-E664
    https://doi.org/10.1152/ajpendo.00165.2021 | PMID: 34569271 | PMCID: PMC8791787
    Citations: | AltScore: 14.85
  3. Measured Versus Estimated Resting Metabolic Rate in Heart Failure With Preserved Ejection Fraction.
    Anderson T, Cascino TM, Koelling TM, Perry D, Grafton G, Houston DK, Upadhya B, Kitzman DW, Hummel SL
    Circ Heart Fail, 2021 Aug, 14(8): e007962
    https://doi.org/10.1161/CIRCHEARTFAILURE.120.007962 | PMID: 34344169 | PMCID: PMC8373809
    Citations: | AltScore: 1.25
  4. Evaluation of a Strength-Training Program on Clinical Outcomes in Older Adults.
    Baumann CW, Manini TM, Clark BC
    JAMA, 2021 Mar 16, 325(11): 1111
    https://doi.org/10.1001/jama.2021.0298 | PMID: 33724318 | PMCID: PMC8148633
    Citations: | AltScore: NA
  5. Elevated IL-6 and CRP Levels Are Associated With Incident Self-Reported Major Mobility Disability: A Pooled Analysis of Older Adults With Slow Gait Speed.
    Beavers DP, Kritchevsky SB, Gill TM, Ambrosius WT, Anton SD, Fielding RA, King AC, Rejeski WJ, Lovato L, McDermott MM, Newman AB, Pahor M, Walkup MP, Tracy RP, Manini TM
    J Gerontol A Biol Sci Med Sci, 2021 Nov 15, 76(12): 2293-2299
    https://doi.org/10.1093/gerona/glab093 | PMID: 33822946 | PMCID: PMC8598983
    Citations: | AltScore: 4.5
  6. Risedronate use to attenuate bone loss following sleeve gastrectomy: Results from a pilot randomized controlled trial.
    Beavers KM, Beavers DP, Fernandez AZ, Greene KA, Swafford AA, Weaver AA, Wherry SJ, Ard JD
    Clin Obes, 2021 Dec, 11(6): e12487
    https://doi.org/10.1111/cob.12487 | PMID: 34569167 | PMCID: PMC8563448
    Citations: 1 | AltScore: 1
  7. Effects of Exercise and Weight Loss on Proximal Aortic Stiffness in Older Adults With Obesity.
    Brinkley TE, Leng I, Bailey MJ, Houston DK, Hugenschmidt CE, Nicklas BJ, Hundley WG
    Circulation, 2021 Aug 31, 144(9): 684-693
    https://doi.org/10.1161/CIRCULATIONAHA.120.051943 | PMID: 34333991 | PMCID: PMC8405553
    Citations: 2 | AltScore: 514.84
  8. Embedding and Sustaining a Focus on Function in Specialty Research and Care.
    Callahan KE, Boustani M, Ferrante L, Forman DE, Gurwitz J, High KP, McFarland F, Robinson T, Studenski S, Yang M, Schmader KE
    J Am Geriatr Soc, 2021 Jan, 69(1): 225-233
    https://doi.org/10.1111/jgs.16860 | PMID: 33064303 | PMCID: PMC7871732
    Citations: 3 | AltScore: 1.5
  9. Automated Frailty Screening At-Scale for Pre-Operative Risk Stratification Using the Electronic Frailty Index.
    Callahan KE, Clark CJ, Edwards AF, Harwood TN, Williamson JD, Moses AW, Willard JJ, Cristiano JA, Meadows K, Hurie J, High KP, Meredith JW, Pajewski NM
    J Am Geriatr Soc, 2021 Jan 19, 69(5): 1357-1362
    https://doi.org/10.1111/jgs.17027 | PMID: 33469933 | PMCID: PMC8127394
    Citations: 8 | AltScore: 25.2
  10. Investigating Predictors of Preserved Cognitive Function in Older Women Using Machine Learning: Women's Health Initiative Memory Study.
    Casanova R, Gaussoin SA, Wallace R, Baker LD, Chen JC, Manson JE, Henderson VW, Sachs BC, Justice JN, Whitsel EA, Hayden KM, Rapp SR
    J Alzheimers Dis, 2021, 84(3): 1267-1278
    https://doi.org/10.3233/JAD-210621 | PMID: 34633318 | PMCID: PMC8934040
    Citations: | AltScore: 2.75
  11. Ratings of Perceived Exertion During Walking: Predicting Major Mobility Disability and Effect of Structured Physical Activity in Mobility-Limited Older Adults.
    Cenko E, Chen H, Gill TM, Glynn NW, Henderson RM, King AC, Pahor M, Qiu P, Rego A, Reid KF, Tudor-Locke C, Valiani V, You L, Manini TM
    J Gerontol A Biol Sci Med Sci, 2021 Sep 13, 76(10): e264-e271
    https://doi.org/10.1093/gerona/glab036 | PMID: 33585918 | PMCID: PMC8436976
    Citations: | AltScore: 3.25
  12. The emerging role of the sympathetic nervous system in skeletal muscle motor innervation and sarcopenia.
    Delbono O, Rodrigues ACZ, Bonilla HJ, Messi ML
    Ageing Res Rev, 2021 May, 67: 101305
    https://doi.org/10.1016/j.arr.2021.101305 | PMID: 33610815 | PMCID: PMC8049122
    Citations: 4 | AltScore: 4.1
  13. A case study of ascertainment bias for the primary outcome in the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial.
    Esserman DA, Gill TM, Miller ME, Greene EJ, Dziura JD, Travison TG, Meng C, Peduzzi PN
    Clin Trials, 2021 Apr, 18(2): 207-214
    https://doi.org/10.1177/1740774520980070 | PMID: 33678038 | PMCID: PMC8009806
    Citations: | AltScore: NA
  14. Building on Lessons Learned in a Mobile Intervention to Reduce Pain and Improve Health (MORPH): Protocol for the MORPH-II Trial.
    Fanning J, Brooks AK, Hsieh KL, Kershner K, Furlipa J, Nicklas BJ, Rejeski WJ
    JMIR Res Protoc, 2021 Jul 19, 10(7): e29013
    https://doi.org/10.2196/29013 | PMID: 34279241 | PMCID: PMC8329761
    Citations: 1 | AltScore: NA
  15. Aging-related Alzheimer's disease-like neuropathology and functional decline in captive vervet monkeys (Chlorocebus aethiops sabaeus).
    Frye BM, Craft S, Latimer CS, Keene CD, Montine TJ, Register TC, Orr ME, Kavanagh K, Macauley SL, Shively CA
    Am J Primatol, 2021 Nov, 83(11): e23260
    https://doi.org/10.1002/ajp.23260 | PMID: 33818801 | PMCID: PMC8626867
    Citations: 7 | AltScore: 13.35
  16. Diet, psychosocial stress, and Alzheimer's disease-related neuroanatomy in female nonhuman primates.
    Frye BM, Craft S, Register TC, Andrews RN, Appt SE, Vitolins MZ, Uberseder B, Silverstein-Metzler MG, Chen H, Whitlow CT, Kim J, Barcus RA, Lockhart SN, Hoscheidt S, Say BM, Corbitt SE, Shively CA
    Alzheimers Dement, 2021 May, 17(5): 733-744
    https://doi.org/10.1002/alz.12232 | PMID: 33270373 | PMCID: PMC8119381
    Citations: 4 | AltScore: 13.8
  17. Temporal emergence of age-associated changes in cognitive and physical function in vervets (Chlorocebus aethiops sabaeus).
    Frye BM, Valure PM, Craft S, Baxter MG, Scott C, Wise-Walden S, Bissinger DW, Register HM, Copeland C, Jorgensen MJ, Justice JN, Kritchevsky SB, Register TC, Shively CA
    Geroscience, 2021 Jun, 43(3): 1303-1315
    https://doi.org/10.1007/s11357-021-00338-w | PMID: 33611720 | PMCID: PMC8190425
    Citations: 3 | AltScore: 5.5
  18. Effectiveness of a Nurse-Led Multidisciplinary Intervention vs Usual Care on Advance Care Planning for Vulnerable Older Adults in an Accountable Care Organization: A Randomized Clinical Trial.
    Gabbard J, Pajewski NM, Callahan KE, Dharod A, Foley KL, Ferris K, Moses A, Willard J, Williamson JD
    JAMA Intern Med, 2021 Jan 11, 181(3): 361-369
    https://doi.org/10.1001/jamainternmed.2020.5950 | PMID: 33427851 | PMCID: PMC7802005
    Citations: 7 | AltScore: 86.578
  19. Activity Levels in Survivors of the Intensive Care Unit.
    Gandotra S, Files DC, Shields KL, Berry M, Bakhru RN
    Phys Ther, 2021 Sep 1, 101(9):
    pii: pzab135. https://doi.org/10.1093/ptj/pzab135 | PMID: 34097055 | PMCID: PMC8418209
    Citations: | AltScore: 27.05
  20. Effect of intensive blood pressure control on subtypes of mild cognitive impairment and risk of progression from SPRINT study.
    Gaussoin SA, Pajewski NM, Chelune G, Cleveland ML, Crowe MG, Launer LJ, Lerner AJ, Martindale-Adams J, Nichols LO, Ogrocki PK, Sachs BC, Sink KM, Supiano MA, Wadley VG, Wilson VM, Wright CB, Williamson JD, Reboussin DM, Rapp SR
    J Am Geriatr Soc, 2021 Nov 26, 70(5): 1384-1393
    https://doi.org/10.1111/jgs.17583 | PMID: 34826341 | PMCID: PMC9106821
    Citations: | AltScore: 31.25
  21. Relationships Between Objectively Measured Physical Activity, Exercise Capacity, and Quality of Life in Older Patients With Obese Heart Failure and Preserved Ejection Fraction.
    German CA, Brubaker PH, Nelson MB, Fanning J, Ye F, Kitzman DW
    J Card Fail, 2021 Jun, 27(6): 635-641
    https://doi.org/10.1016/j.cardfail.2020.12.025 | PMID: 34088379 | PMCID: PMC8186734
    Citations: | AltScore: 4.5
  22. Trajectories of Blood Pressure Control a Year After Randomization and Incident Cardiovascular Outcomes in SPRINT.
    German CA, Elfassy T, Singleton MJ, Rodriguez CJ, Ambrosius WT, Yeboah J
    Am J Hypertens, 2021 Sep 22, 34(9): 973-980
    https://doi.org/10.1093/ajh/hpab059 | PMID: 33861306 | PMCID: PMC8457432
    Citations: | AltScore: 3.7
  23. Aging Influences the Metabolic and Inflammatory Phenotype in an Experimental Mouse Model of Acute Lung Injury.
    Gibbs KW, Chuang Key CC, Belfield L, Krall J, Purcell L, Liu C, Files DC
    J Gerontol A Biol Sci Med Sci, 2021 Apr 30, 76(5): 770-777
    https://doi.org/10.1093/gerona/glaa248 | PMID: 32997738 | PMCID: PMC8087268
    Citations: 3 | AltScore: 8.45
  24. Heterogeneity in Association Between Cognitive Function and Gait Speed Among Older Adults: An Integrative Data Analysis Study.
    Handing EP, Rapp SR, Chen SH, Rejeski WJ, Wiberg M, Bandeen-Roche K, Craft S, Kitzman D, Ip EH
    J Gerontol A Biol Sci Med Sci, 2021 Mar 31, 76(4): 710-715
    https://doi.org/10.1093/gerona/glaa211 | PMID: 32841312 | PMCID: PMC8011698
    Citations: 5 | AltScore: NA
  25. Legacy of a 10-Year Multidomain Lifestyle Intervention on the Cognitive Trajectories of Individuals with Overweight/Obesity and Type 2 Diabetes Mellitus.
    Hayden KM, Neiberg RH, Evans JK, Luchsinger JA, Carmichael O, Dutton GR, Johnson KC, Kahn SE, Rapp SR, Yasar S, Espeland MA, Action for Health in Diabetes (Look AHEAD) Research Group.
    Dement Geriatr Cogn Disord, 2021, 50(3): 237-249
    https://doi.org/10.1159/000517160 | PMID: 34412057 | PMCID: PMC8530880
    Citations: | AltScore: NA
  26. Conversion between the Modified Mini-Mental State Examination (3MSE) and the Mini-Mental State Examination (MMSE).
    Ip EH, Pierce J, Chen SH, Lovato J, Hughes TM, Hayden KM, Hugenschmidt CE, Craft S, Kitzman D, Rapp S
    Alzheimers Dement (Amst), 2021, 13(1): e12161
    https://doi.org/10.1002/dad2.12161 | PMID: 33816754 | PMCID: PMC8010479
    Citations: | AltScore: 7
  27. Vascular dysfunction as a potential culprit of sarcopenia.
    Jeon YK, Shin MJ, Saini SK, Custodero C, Aggarwal M, Anton SD, Leeuwenburgh C, Mankowski RT
    Exp Gerontol, 2021 Mar, 145: 111220
    https://doi.org/10.1016/j.exger.2020.111220 | PMID: 33373710 | PMCID: PMC8168450
    Citations: 7 | AltScore: 12.15
  28. Diet-Microbiota-Brain Axis in Alzheimer's Disease.
    Kincaid HJ, Nagpal R, Yadav H
    Ann Nutr Metab, 2021, 77 Suppl 2: 21-27
    https://doi.org/10.1159/000515700 | PMID: 33906194
    Citations: 6 | AltScore: 20.78
  29. Physical Rehabilitation for Older Patients Hospitalized for Heart Failure.
    Kitzman DW, Whellan DJ, Duncan P, Pastva AM, Mentz RJ, Reeves GR, Nelson MB, Chen H, Upadhya B, Reed SD, Espeland MA, Hewston L, O'Connor CM
    N Engl J Med, 2021 May 16, 385(3): 203-216
    https://doi.org/10.1056/NEJMoa2026141 | PMID: 33999544 | PMCID: PMC8353658
    Citations: 40 | AltScore: 595.556000000001
  30. Automated Muscle Measurement on Chest CT Predicts All-Cause Mortality in Older Adults From the National Lung Screening Trial.
    Lenchik L, Barnard R, Boutin RD, Kritchevsky SB, Chen H, Tan J, Cawthon PM, Weaver AA, Hsu FC
    J Gerontol A Biol Sci Med Sci, 2021 Jan 18, 76(2): 277-285
    https://doi.org/10.1093/gerona/glaa141 | PMID: 32504466 | PMCID: PMC7812435
    Citations: 9 | AltScore: 5.45
  31. Rehabilitation Intervention in Older Patients With Acute Heart?Failure With?Preserved Versus Reduced Ejection?Fraction.
    Mentz RJ, Whellan DJ, Reeves GR, Pastva AM, Duncan P, Upadhya B, Nelson MB, Chen H, Reed SD, Rosenberg PB, Bertoni AG, O'Connor CM, Kitzman DW
    JACC Heart Fail, 2021 Oct, 9(10): 747-757
    https://doi.org/10.1016/j.jchf.2021.05.007 | PMID: 34246602 | PMCID: PMC8487922
    Citations: 5 | AltScore: 45.8
  32. Effect of High-Intensity Strength Training on Knee Pain and Knee Joint Compressive Forces Among Adults With Knee Osteoarthritis: The START Randomized Clinical Trial.
    Messier SP, Mihalko SL, Beavers DP, Nicklas BJ, DeVita P, Carr JJ, Hunter DJ, Lyles M, Guermazi A, Bennell KL, Loeser RF
    JAMA, 2021 Feb 16, 325(7): 646-657
    https://doi.org/10.1001/jama.2021.0411 | PMID: 33591346 | PMCID: PMC7887656
    Citations: 4 | AltScore: 349.568
  33. Changes in body weight and knee pain in adults with knee osteoarthritis 3.5 years after completing diet and exercise interventions.
    Messier SP, Newman JJ, Scarlett MJ, Mihalko SL, Miller GD, Nicklas BJ, DeVita P, Hunter DJ, Lyles MF, Eckstein F, Guermazi A, Loeser RF, Beavers DP
    Arthritis Care Res (Hoboken), 2021 Aug 9, 74(4): 607-616
    https://doi.org/10.1002/acr.24765 | PMID: 34369105 | PMCID: PMC8825890
    Citations: | AltScore: 23.75
  34. Association of Urine Biomarkers of Kidney Tubule Injury and Dysfunction With Frailty Index and Cognitive Function in Persons With CKD in SPRINT.
    Miller LM, Rifkin D, Lee AK, Kurella Tamura M, Pajewski NM, Weiner DE, Al-Rousan T, Shlipak M, Ix JH
    Am J Kidney Dis, 2021 Oct, 78(4): 530-540.e1
    https://doi.org/10.1053/j.ajkd.2021.01.009 | PMID: 33647393 | PMCID: PMC8390569
    Citations: 2 | AltScore: 21.83
  35. Incorporating Nutrition, Vests, Education, and Strength Training (INVEST) in Bone Health: Trial Design and Methods.
    Miller RM, Beavers DP, Cawthon PM, Crotts C, Fanning J, Gerosa J, Greene KA, Hsieh KL, Kiel J, Lawrence E, Lenchik L, Lynch SD, Nesbit BA, Nicklas BJ, Weaver AA, Beavers KM
    Contemp Clin Trials, 2021 May, 104: 106326
    https://doi.org/10.1016/j.cct.2021.106326 | PMID: 33631359 | PMCID: PMC8180512
    Citations: | AltScore: 3.45
  36. New Horizons in Microbiota and Metabolic Health Research.
    Mishra SP, Jain S, Taraphder S, Yadav H
    J Clin Endocrinol Metab, 2021 Jan 23, 106(2): e1052-e1059
    https://doi.org/10.1210/clinem/dgaa769 | PMID: 33128374 | PMCID: PMC7823252
    Citations: | AltScore: 22.35
  37. Effects of a Motor Imagery Task on Functional Brain Network Community Structure in Older Adults: Data from the Brain Networks and Mobility Function (B-NET) Study.
    Neyland BR, Hugenschmidt CE, Lyday RG, Burdette JH, Baker LD, Rejeski WJ, Miller ME, Kritchevsky SB, Laurienti PJ
    Brain Sci, 2021 Jan 17, 11(1):
    pii: 118. https://doi.org/10.3390/brainsci11010118 | PMID: 33477358 | PMCID: PMC7830141
    Citations: 1 | AltScore: NA
  38. Physical frailty in older patients with acute heart failure: From risk marker to modifiable treatment target.
    Pandey A, Gilbert O, Kitzman DW
    J Am Geriatr Soc, 2021 Jun 19, 69(9): 2451-2454
    https://doi.org/10.1111/jgs.17306 | PMID: 34146340 | PMCID: PMC8440358
    Citations: | AltScore: 61.45
  39. Searching for the Optimal Exercise Training Regimen in Heart Failure With Preserved Ejection Fraction.
    Pandey A, Kitzman DW
    JAMA, 2021 Feb 9, 325(6): 537-539
    https://doi.org/10.1001/jama.2020.26347 | PMID: 33560307 | PMCID: PMC8261711
    Citations: 4 | AltScore: 51.75
  40. Exercise Intolerance in Older Adults With?Heart?Failure With Preserved Ejection?Fraction: JACC State-of-the-Art Review.
    Pandey A, Shah SJ, Butler J, Kellogg DL Jr, Lewis GD, Forman DE, Mentz RJ, Borlaug BA, Simon MA, Chirinos JA, Fielding RA, Volpi E, Molina AJA, Haykowsky MJ, Sam F, Goodpaster BH, Bertoni AG, Justice JN, White JP, Ding J, Hummel SL, LeBrasseur NK, Taffet GE, Pipinos II, Kitzman D
    J Am Coll Cardiol, 2021 Sep 14, 78(11): 1166-1187
    https://doi.org/10.1016/j.jacc.2021.07.014 | PMID: 34503685 | PMCID: PMC8525886
    Citations: 9 | AltScore: 19.3
  41. Characterizing the physical function decline and disabilities present among older adults with fecal incontinence: a secondary analysis of the health, aging, and body composition study.
    Parker-Autry C, Leng I, Matthews CA, Thorne N, Kritchevsky S
    Int Urogynecol J, 2021 Aug 11
    https://doi.org/10.1007/s00192-021-04933-5 | PMID: 34379165
    Citations: | AltScore: NA
  42. The geriatric incontinence syndrome: Characterizing geriatric incontinence in older women.
    Parker-Autry C, Neiberg RH, Leng I, Colombo L, Kuchel GA, Kritchevsky SB
    J Am Geriatr Soc, 2021 Nov, 69(11): 3225-3231
    https://doi.org/10.1111/jgs.17374 | PMID: 34519024
    Citations: | AltScore: 8.1
  43. The other striated muscle: The role of sarcopenia in older persons with heart failure.
    Reeves GR, Pandey A, Kitzman DW
    J Am Geriatr Soc, 2021 Apr 17, 69(7): 1811-1814
    https://doi.org/10.1111/jgs.17160 | PMID: 33864385
    Citations: 1 | AltScore: 35.85
  44. Six-month changes in ghrelin and glucagon-like peptide-1 with weight loss are unrelated to long-term weight regain in obese older adults.
    Rejeski JJ, Fanning J, Nicklas BJ, Rejeski WJ
    Int J Obes (Lond), 2021 Apr, 45(4): 888-894
    https://doi.org/10.1038/s41366-021-00754-0 | PMID: 33526855 | PMCID: PMC8005376
    Citations: | AltScore: 4.35
  45. Long-term, induced expression of Hand2 in peripheral sympathetic neurons ameliorates sarcopenia in geriatric mice.
    Rodrigues ACZ, Messi ML, Wang ZM, Bonilla HJ, Freeman WM, Delbono O
    J Cachexia Sarcopenia Muscle, 2021 Dec, 12(6): 1908-1924
    https://doi.org/10.1002/jcsm.12790 | PMID: 34546662 | PMCID: PMC8718059
    Citations: 1 | AltScore: 0.25
  46. Heart and neural crest derivative 2-induced preservation of sympathetic neurons attenuates sarcopenia with aging.
    Rodrigues ACZ, Wang ZM, Messi ML, Bonilla HJ, Liu L, Freeman WM, Delbono O
    J Cachexia Sarcopenia Muscle, 2021 Feb, 12(1): 91-108
    https://doi.org/10.1002/jcsm.12644 | PMID: 33258279 | PMCID: PMC7890150
    Citations: 5 | AltScore: 15.358
  47. Robust demographically-adjusted normative data for the Montreal Cognitive Assessment (MoCA): Results from the systolic blood pressure intervention trial.
    Sachs BC, Chelune GJ, Rapp SR, Couto AM, Willard JJ, Williamson JD, Sink KM, Coker LH, Gaussoin SA, Gure TR, Lerner AJ, Nichols LO, Still CH, Wadley VG, Pajewski NM
    Clin Neuropsychol, 2021 Sep 1 1-16
    https://doi.org/10.1080/13854046.2021.1967450 | PMID: 34470584 | PMCID: PMC8885785
    Citations: 2 | AltScore: 7
  48. Nonhuman primates at the intersection of aging biology, chronic disease, and health: An introduction to the American Journal of Primatology Special Issue on aging, cognitive decline, and neuropathology in nonhuman primates.
    Shively CA, Lacreuse A, Frye BM, Rothwell ES, Moro M
    Am J Primatol, 2021 Nov, 83(11): e23309
    https://doi.org/10.1002/ajp.23309 | PMID: 34403529 | PMCID: PMC8935964
    Citations: 1 | AltScore: 1.75
  49. Does the Impact of Intensive Lifestyle Intervention on Cardiovascular Disease Risk Vary According to Frailty as Measured via Deficit Accumulation?
    Simpson FR, Pajewski NM, Beavers KM, Kritchevsky S, McCaffery J, Nicklas BJ, Wing RR, Bertoni A, Ingram F, Ojeranti D, Espeland MA
    J Gerontol A Biol Sci Med Sci, 2021 Jan 18, 76(2): 339-345
    https://doi.org/10.1093/gerona/glaa153 | PMID: 32564066 | PMCID: PMC8444302
    Citations: 2 | AltScore: 10.7
  50. Left Atrial Stiffness Index Independently Predicts Exercise Intolerance and Quality of Life in Older, Obese Patients With Heart Failure With Preserved Ejection Fraction.
    Singleton MJ, Nelson MB, Samuel TJ, Kitzman DW, Brubaker P, Haykowsky MJ, Upadhya B, Chen H, Nelson MD
    J Card Fail, 2021 Nov 10, 28(4): 567-575
    pii: S1071-9164(21)00436-X. https://doi.org/10.1016/j.cardfail.2021.10.010 | PMID: 34774747 | PMCID: PMC9018494
    Citations: | AltScore: 7.7
  51. Effect of Intensive Blood Pressure Control on Aortic Stiffness in the SPRINT-HEART.
    Upadhya B, Pajewski NM, Rocco MV, Hundley WG, Aurigemma G, Hamilton CA, Bates JT, He J, Chen J, Chonchol M, Glasser SP, Hung AM, Pisoni R, Punzi H, Supiano MA, Toto R, Taylor A, Kitzman DW, SPRINT Research Group.
    Hypertension, 2021 May 5, 77(5): 1571-1580
    https://doi.org/10.1161/HYPERTENSIONAHA.120.16676 | PMID: 33775127 | PMCID: PMC8035296
    Citations: 2 | AltScore: 11.6
  52. Incidence and Outcomes of Acute Heart Failure With Preserved Versus Reduced Ejection Fraction in SPRINT.
    Upadhya B, Willard JJ, Lovato LC, Rocco MV, Lewis CE, Oparil S, Cushman WC, Bates JT, Bello NA, Aurigemma G, Johnson KC, Rodriguez CJ, Raj DS, Rastogi A, Tamariz L, Wiggers A, Kitzman DW, SPRINT Research Group.
    Circ Heart Fail, 2021 Dec, 14(12): e008322
    https://doi.org/10.1161/CIRCHEARTFAILURE.121.008322 | PMID: 34823375 | PMCID: PMC8692397
    Citations: 3 | AltScore: 6.35
  53. Effect of Dietary Protein Intake on Bone Mineral Density and Fracture Incidence in Older Adults in the Health, Aging, and Body Composition Study.
    Weaver AA, Tooze JA, Cauley JA, Bauer DC, Tylavsky FA, Kritchevsky SB, Houston DK
    J Gerontol A Biol Sci Med Sci, 2021 Nov 15, 76(12): 2213-2222
    https://doi.org/10.1093/gerona/glab068 | PMID: 33677533 | PMCID: PMC8599066
    Citations: | AltScore: 47.65
  54. Effect of Intensive Versus Standard Blood Pressure Control on Stroke Subtypes.
    Wright CB, Auchus AP, Lerner A, Ambrosius WT, Ay H, Bates JT, Chen J, Meschia JF, Pancholi S, Papademetriou V, Rastogi A, Sweeney M, Willard JJ, Yee J, Oparil S
    Hypertension, 2021 Apr, 77(4): 1391-1398
    https://doi.org/10.1161/HYPERTENSIONAHA.120.16027 | PMID: 33583199 | PMCID: PMC8224947
    Citations: | AltScore: 4.1


EXTERNAL ADVISORY BOARD MEMBERS

Nir Barzilai
Albert Einstein College of Medicine
Serving since 2012 (10 years)

Heather Whitson
Duke University
Serving since 2018 (4 years)

Kirk Erickson
University of Pittsburgh
Serving since 2018 (4 years)

Nathan LaBrasseur
Mayo Clinic
Serving since 2018 (4 years)

Roger Fielding
Tufts University
Serving since 2018 (4 years)


RECOGNITION AND AWARDS (2021-2022)
Atalie Thompson (2021)
  • American Glaucoma Society, MAPS award
Charles McCall, MD (2021)
  • Society for Leukocyte Biology Legacy Award Recipient
Dalane Kitzman, MD (2021)
  • Michael L. Pollock Established Investigator Award, American Association of Cardiovascular and Pulmonary Rehabilitation
Denise Houston, PhD (2021)
  • Career Development for Women Leaders (CDWL) Program, Wake Forest School of Medicine
  • Team Science Award (PREVENTABLE), Wake Forest School of Medicine
Gagan Deep (2021)
  • Research Excellence Award, Wake Forest School of Medicine
Heidi Kleipin, MD (2021)
  • Fellow, American Society of Clinical Oncology (FASCO)
  • Nominee, Harrison Teaching Award, nominated by Internal Medicine Residents
Jaime Speiser, PhD (2022)
  • Top 8 Cited Paper in the Past 3 Years, Expert Systems with Applications Journal (Publication #5, Speiser et al.)
Jamie Justice, PhD (2022)
  • AFAR Vincent Cristofalo Rising Star in Aging Research Award
  • Travel Awardee, NIA / AFAR Research Centers Collaborative Network (RCCN), Measuring Biologic Age Workshop
  • Jarrahi Research Scholars Fund in Geroscience Innovation
Jeff Williamson, MD (2021)
  • Wake Forest School of Medicine and Atrium Health Team Science Award - US POINTER
  • Wake Forest School of Medicine and Atrium Health Team Science Award - PREVENTABLE
Leon Lenchik (2021)
  • 2021 Honorable Mention: NIH Prize for Enhancing Faculty Gender Diversity in Biomedical and Behavioral Science. Tooze JA, Anthony EY, MD, Gesell SB, Danhauer SC, Emory CL, Danelson KA, Dressler E, Parker-Autry CY, Gwathmey TM, Criswell TL, Lenchik L, Barrett N, Whitley H.
Nicholas Pajewski, PhD (2021)
  • Wake Forest School of Medicine Team Science Award, PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr adults (PREVENTABLE) trial
Rita Bahkru, MD (2021)
  • Wake Forest Research Excellence Award
Stephen Kritchevsky, PhD (2021)
  • James Edwin Byrum Jr. Distinguished Faculty Mentoring Award
Stephen Kritchevsky, PhD (2021)
  • Toby R. Alligood, MD Endowed Professor in Geroscience

MINORITY RESEARCH

General Brief Description of Minority Activities:
The Maya Angelou Research Center for Health Equality (MA-RCHE) has been established by the WFUSM to address issues related to racial and ethnic health disparities. Its overarching goal is to enhance wellness, improve quality of life, and reduce the burden of disease in underrepresented minorities through a comprehensive program in four core areas: health education, career/leadership development, research, and dissemination/application of new research findings for more effective and efficient health care approaches.

A key feature of the MA-RCHE is its model campus/community partnership involving WFUSM, the Reynolda Campus of Wake Forest University, Winston-Salem State University (a historically Black college/university) and the Forsyth County community at-large. This partnership brings the vast experiences, knowledge base and resources of each partner to bear on health problems of underrepresented minorities.


Minority Trainee(s):
  • Amber Brooks, MD, Assistant Professor, Department of Anesthesiology
    Project Title: Revisiting A Mobile Intervention to Reduce Pain and Improve Health (MORPH2) Leaders: Amber Brooks, MD and Jason Fanning, PhD Dept of Anesthesiology and Wake Forest Health and Exercise Sciences, respectively Wells Fargo Faculty Scholar Award / 2020-2022 MORPH concluded with a two-group randomized controlled pilot trial (RCT) in obese (BMI=30-45 kg/m2), low-active, older (55-85 years) adults with chronic pain who were randomized to either 12-weeks of active intervention or a wait-list control. This study represents an extension of MORPH—hereafter MORPH II—with the intention of immediately addressing limitations in the original MORPH study. We will randomize 30 older, low-active, obese adults to the active intervention or to a standard control for 12 weeks. To build upon the last phase of MORPH, we will deliver this intervention fully remotely, providing cellular data-equipped tablet computers to protect participant safety and reduce technical issues that may arise due to lack of face-to-face orientation appointments. We are mindful of the current COVID-19 climate and have chosen to deliver the entire intervention remotely. We will include intensive individual coaching throughout the program and greater emphasis on frequent movement to drive better uptake of a day-long movement program and will transition participants to a 12-week no-contact follow-up to observe whether behavior change sustains following completion of the focused intervention. CRC trained the staff and oversee the physical performance testing and core battery. BIC supports the collection and data entry of the core battery data into the common database. REC Continues support for this previous scholar. Study Status: Recruitment and intervention are underway
  • Gagan Deep, PhD, Associate Professor, Cancer Biology
    PESC Pilot 2019.1 Isolation and molecular characterization of exosomes secreted by visceral adipose tissue
  • Genesio Karere, PhD, Assistant Professor, Department of Internal Medicine, Section on Molecular Medicine
    Current REC scholar Project title: MicroRNA biomarkers and pathways underlying response to exercise intervention in older adults
  • Raghunatha Yammani, PhD, Associate Professor, Internal Medicine, Molecular Medicine
    PESC 2019.2 Is Restoring Protein Homeostasis A Viable Therapy For Age-Related Osteoarthritis?

Minority Grant(s):