THE JOHNS HOPKINS UNIVERSITY
Claude D. Pepper Older Americans Independence Center

Principal Investigator    Jeremy Walston, M.D.  410-550-1003  jwalston@jhmi.edu
Program Administrator    Brian Buta, MHS  410-502-3412  bbuta@jhu.edu
       
CENTER DESCRIPTION

Since its inception in 2003, the Johns Hopkins University (JHU) Older Americans Independence Center (OAIC) has pursued a rigorous and distinctive scientific approach considering physical frailty as a biologically-rooted state of decreased resiliency and reserve, which induces a syndromic phenotype and specific etiological mechanisms. As evidenced by peer-reviewed publications and associated NIH grant funding, this specific conceptualization of frailty has provided a highly productive framework for population-based, clinical, and biological discovery, for the development of potential prevention and treatment strategies, and for the training of junior investigators for academic careers in frailty and aging research. This center’s mission remains, in many respects, as it has been throughout the life of our OAIC: To make fundamental etiological discoveries related to frailty, move these towards frailty-focused interventions, develop evidence-based guidelines for the prevention and management of adverse outcomes in frail older individuals, identify new investigators dedicated to these ends, and provide supported investigators with the expertise, resources, and training necessary to lead the next generation of frailty-related scholarship and practice. Given the rapidly growing interest in frailty, its detection, its management, and the critical mass of frailty-related knowledge that this OAIC has generated, we have launched an Information Dissemination Core (IDC) to enable our OAIC to more comprehensively disseminate frailty-related findings so as to better impact clinical and public health practice. We pursue our mission through the following specific aims:

  1. To stimulate, lead and develop effective frailty-focused interdisciplinary research programs that promote the maintenance of independence. This has helped to create a vibrant and growing center with scientific vigor and a rich interdisciplinary milieu of experienced faculty and successful trainees focused on frailty research.
  2. To translate the new knowledge generated in this OAIC into targeted prevention and treatment strategies that help older adults maintain independence. An existing clinical translational resource core, an IDC, and the national OAIC network facilitate this effort.
  3. To provide the highest quality expertise, support, infrastructure and technology in biological, data analytic and clinical research methodologies to OAIC investigators.
  4. To support the development of new and innovative methodologies, research strategies and technologies essential to the study of frailty. Aims 3 and 4 are organized through Biostatistics, Biological Mechanisms, and Clinical Translational cores.
  5. To provide tailored training and mentorship to junior investigators interested in developing careers focused on frailty in older adults. We continue with a leadership team that has demonstrated expertise and commitment to training the next generation of investigators.
  6. To attract outstanding investigators and trainees to frailty research from across the Johns Hopkins University and beyond. We augment our successful local approach to this by providing highly visible educational and training activities on a local and national level, and through the IDC.

CORES
Leadership and Administrative Core (LAC)
Leader 1:    Karen Bandeen-Roche, PhD   kbandee1@jhu.edu
Leader 2:    Jeremy Walston, MD   jwalston@jhmi.edu
The Leadership/Administrative Core (LAC) spearheads the vision for the Johns Hopkins Older Americans Independence Center (JHU OAIC), sets goals through which to implement it, and assures energy and quality in accomplishing goals. It leads in identifying the next generation of research on frailty that should be created, supports research planning and recruitment of investigators, and sets and monitors progress benchmarks. It is the OAIC base for recruiting and nurturing a critical mass of investigators dedicated to the creation of high impact, innovative research essential to the prevention and treatment of frailty in older adults. It administrates the OAIC and its Cores for soundness of operations and accomplishes required reporting. It promotes a stimulating intellectual environment around scholarship on frailty so as to attract outstanding researchers and knit them into an interdisciplinary community. It creates visibility for the accomplishments of the OAIC locally and globally: In the current cycle it leverages a new Information Dissemination Core (IDC) to amplify these efforts. The LAC is led by OAIC Co-Principal Investigators with broad interdisciplinary scientific expertise and institutional reach. They work closely with the other OAIC Cores Directors, and with a diverse Leadership Council and Internal Advisory Committee to develop and promote a frailty-focused agenda across the Johns Hopkins University. An experienced External Advisory Board reviews this OAIC annually, and provides crucial feedback and additional scientific vision. The LAC provides essential leadership in planning, integrating, sustaining, implementing and monitoring OAIC operations. Its goals are to envision and then support research leading to new strategies to enhance independence in older Americans and to create a new generation of research leaders in the field

Research Education Component (REC)
Leader 1:    Gary Gerstenblith, MD   gblith@jhmi.edu
The purpose of the Research Education Core (REC) is to foster the career development of junior faculty from multiple disciplines into academic scientists in gerontology and geriatrics, focusing on the theme of exercise and activity rehabilitation and recovery research. The REC supports mentor-based research training and education to promote the career development of REC Scholars as well as other junior faculty, fellows, and students pursuing research careers in aging. The UM-OAIC has a successful history of mentored training that crosses traditional disciplinary boundaries to develop novel research for improving function and independence in older persons. This has enriched the cadre of scientists at UM and elsewhere conducting aging research in exercise and rehabilitation science.

Pilot and Exploratory Studies Core (PESC)
Leader 1:    Neal Fedarko, PhD   ndarko@jhmi.edu
The major goal of Pilot and Exploratory Studies Core (PESC) is to cultivate and support innovative pilot and exploratory studies that are needed to develop crucial larger scale and confirmatory studies to advance the development of effective prevention and/or therapies for frailty, and hence facilitate independence in older adults. The PESC provides funding, access to biostatistical, biological, and clinical research core resources, and mentoring and oversight pilot and exploratory studies. Because of the importance of these studies to the development of new scientific priorities, additional resources are provided to this core to help maximize flexibility, efficiency, and rapid development of areas of focus for this OAIC. The PESC Core, in close collaboration with the OAIC Leadership Council, sets ideas the next stages of research most essential to advancing science on frailty, and then works to identify investigators whose expertise and career goals are applicable to furthering knowledge in these target areas. The leadership and resources of these cores are then focused on the development, conduct and eventual translation of high impact pilot studies. The proposed studies must be novel and either hypothesis-driven or focused on development of methods needed to validly address hypotheses: they ideally address potential mechanisms, etiologies, or screening approaches for frailty, or lay groundwork for evaluating potential therapies to prevent or treat the frailty and its consequences and hence maintain independence. It is expected that PESC-supported studies establish preliminary data that will lead to substantive, long term external funding that can bring the research initiated to completion. Given our roadmap goals of accelerating translation of frailty to increase healthspan in clinical and public health settings, elucidating the biological underpinnings and role of multisystem dysregulation in frailty and resilience, and improving ascertainment of frailty measurement in settings that challenge measurement, special focus was given to these areas for the PESC studies articulated in this application.

Resource Core 1 (RC1): Biostatistics Core (RC1)
Leader 1:    Karen Bandeen-Roche, PhD   kbandee1@jhu.edu
Leader 2:    Qian-Li Xue, PhD   qxue1@jhu.edu

The Johns Hopkins Older Americans Independence Center (OAIC) has empowered by many-fold the creation of significant research, training and practice paradigms for addressing frailty in older adults. The functions supplied by this Biostatistics Core have been central in this. They include: our key roles in the mentorship and training of junior colleagues in the statistics of frailty and aging; our development and dissemination of emerging resources and technologies for data management and analysis; our provision of database and statistical expertise and support to scholarship on frailty and aging, needed methodological innovation, and collaborative intellectual leadership for the creation and translation of research on frailty. Outcomes of this Core, in collaboration in this OAIC and beyond, include advancement of knowledge on the ascertainment, biological and etiological underpinnings, health consequences, and treatment of frailty, research surmounting significant methodological challenges to the study of frailty, and the creation of intellectual capital and infrastructure for further advances. These have laid crucial groundwork for intervening on frailty. For more than 15 years our Biostatistics Core has dedicated a critical mass of leadership from gerontologically informed biostatisticians toward the amelioration of frailty in older adults through our OAIC, and its leadership has dedicated the same to research on aging for nearly 30 years. Our leadership and our external advisory committee consider it crucial that this Core continue to contribute to the OAIC’s overarching aims through the intellectual innovation, collaboration and support it provides.  



Resource Core 2 (RC2): Biological Mechanisms Core (RC2)
Leader 1:    Peter Abadir, MD, PhD   pabadir1@jhmi.edu
Leader 2:    Dan Arking, PhD   darking@jhmi.edu

Advances in in understanding of molecular and physiological processes that influence aging phenotypes, and in methodologies that help to measure these changes, have greatly improved our ability to identify biological pathways that are potentially relevant to the etiology of frailty.  The major goal of this core is to promote molecular and biological studies of aging and frailty-relevant pathways, and to translate these findings into relevant diagnostic, preventive and treatment strategies. Building on our prior cycles, mitochondrial biology, chronic inflammation, renin angiotensin system, and genetics continue to be a core expertise content offered to investigators from within the core.  We have also gained expertise and collaborators at Johns Hopkins who have considerable “omics” and in computational biology expertise.   These technologies have provided a logical basis for searching and identifying specific biomarkers associated with human phenotypes and diseases; they can not only provide markers for human disease that are useful for nosology in heterogeneous clinical phenotypes but, more importantly, provide deep insight into pathophysiology and disease mechanisms that will form the bases for future diagnostics and treatments.   Consequently, the rationale for RC-2 is to provide the expertise, technology access and infrastructure, mentoring, and training necessary to facilitate the highest quality etiologic research in frailty.



Resource Core 3 (RC3): Clinical Translation and Recruitment Core (RC3)
Leader 1:    Todd Brown, MD   tbrown27@jhmi.edu
In order to more effectively meet JHU OAIC’s goal of translating frailty-related etiological discoveries into clinical studies that help maintain independence in older adults, and to overcome the substantial barriers to success in clinical investigation for junior investigators,  the leadership of this OAIC made a strategic decision to develop this resource core.  RC-3 provides to supported OAIC investigators: 1) comprehensive training and mentorship in clinical research that spans from study design through implementation through outcome interpretation, 2) clinical research space and assistance with all aspects of forms and protocol development, data collection, and recruitment of human subjects,  3) an active registry of more than 1000 older adults who have consented to be contacted for aging and frailty related studies, and 4) synergy with other cores in order to optimize all aspects of frailty-related study design, data collection, and biological measurement and junior faculty training.  This synergy is greatly augmented by our core leaders, Dr. Robert Wise, who has considerable expertise in the development, implementation, and conduct of clinical physiological studies and clinical trials and who ended his tenure as leader in 2018. Dr. Todd Brown, an endocrinologist with considerable human subjects research expertise and who plays a leading role in the ICTR at Johns Hopkins, now leads RC-3.  The daily operations are led by a highly skilled and experienced research program manager with expertise in the measurement of frailty, mobility, and cognition, as well as expertise in protocol development and implementation and in subject recruitment and retention, in coordination with our OAIC administrator and Drs. Brown and Walston.  This initiative, which is closely aligned with the JHU Division of Geriatric Medicine and Gerontology goals of better integrating clinical practice with clinical research, is funded in part by philanthropic resources. 

Information Dissemination Core (IDC)
Leader 1:    Jeremy Walston, MD   jwalston@jhmi.edu
Leader 2:    Tara Sullivan, PhD   

To improve the reach and use of the evidence-based knowledge on frailty that emanates from JHU OAIC-supported research and elsewhere, we have developed a state-of-the art Information Dissemination Core (IDC) with a highly experienced partner: Johns Hopkins Center for Communication Programs (CCP). CCP has long standing, high-profile expertise and experience in knowledge management (KM) and dissemination science, with clients including USAID, The Bill and Melinda Gates Foundation, and UNICEF. The development of this close partnership between knowledge management experts at CCP and the frailty related content experts who lead this OAIC provides a highly rigorous yet accessible approach to more efficiently and effectively disseminate frailty-related findings and recommendations to a broader audience using cutting edge approaches. We envision that this audience will include researchers, students, clinicians, professional societies and foundations, policymakers, and older adults seeking information on frailty. Indeed, our overarching goal is to have this IDC become a national and international ‘go-to’ resource for the latest information and resources related to frailty science from this OAIC and as well as other authoritative sources: We seek ultimately to accelerate incorporation of best practices for addressing frailty in health practice and promotion, so as to benefit older adults. 



CAREER DEVELOPMENT
REC Scholar, Research & Grants Funded During Pepper Supported Time Years Publications
 

None specified.

Past Scholars
Alden Gross, PhD, Epidemiology (2014-2016)
Charles H. Brown IV, MD , Anesthesiology and Critical Care Medicine (2014-2016)
Charles H. Brown IV, MD , Anesthesiology and Critical Care Medicine (2014-2016)
Rani Hasan, MD, MHS, Cardiology (2015-2018)
Tae Chung, MD, Physical Medicine and Rehabilitation (2016-2018)
Abdulla Damluji, MD, PhD, Cardiology (2017-2019)
Orla Sheehan, MD, PhD, Geriatric Medicine (2018-2020)
Pei-Hsun Wu, PhD, Institute for NanoBioTechnology (2018-2020)
Bharath Ambale-Venkatesh, PhD, Radiology and Radiological Science (2018-2020)
Reyhan Westbrook, PhD, Geriatric Medicine (2018-2020)
Keenan Walker, PhD, Neorology (2019-2019)

PILOT/EXPLORATORY PROJECTS (5 Pilot Projects Listed)
1. Project Title: Pilot Behavioral Intervention to Address Pain and Frailty in Older African-American Women
  Leader: Janiece Taylor, PhD, RN, Mary Catherine Beach, PhD; Sarah L. Szanton PhD, ANP, FAAN, Roland J. Thorpe Jr., PhD
 

Older African American women are crucial to target for intervention not only because of their heightened frailty prevalence, but because they are at higher risk of pain than other racial/ethnic groups and African American men and have exacerbated relationship and outcomes of frailty and pain. They often experience difficulties communicating with health care providers, moreover, that may interfere with treatment of symptoms related to pain and frailty: Communication intervention has well documented potential to lessen these difficulties and result in better disease management. Specific aims of this study are: 1) To pilot a tailored behavioral activation intervention focused on improving frailty, chronic pain, and depressive symptoms among community dwelling older African American women and collect summary data needed to design a confirmatory intervention trial. Strategies will be non-pharmacologic and aim to improve communication, physical activity and education. 2) To determine a) feasibility and acceptability of the intervention b) if strategies and evaluation techniques were appropriate. 

 
2. Project Title: Exploratory Study of Metabolomics Energy Signatures in Frailty
  Leader: Anne Le, MD, Reyhan Westbrook, PhD
 

Building on a small PES awarded to Drs. Le and Westbrook that utilized a frail mouse model previously characterized in RC-2, altered metabolomics signatures were identified that suggest that TCA cycle processes are a component of dysregulated energy utilization in frailty. Given this background, we hypothesize that specific patterns of altered energy metabolites linked to glucose metabolism through mitochondrial bioenergetics, biosynthesis, and redox homeostasis pathways can help to distinguish frail from non-frail older adults, and that the circulating concentrations of metabolites related to glucose metabolism are measurably different between frail and non-frail older adults. Utilizing research resources from all three resource cores, and Dr. Le’s established metabolomics measurement infrastructure (Metabolomics facility) and expertise in energy metabolism measurement, the following specific aims were proposed: 1) To utilize metabolomics measurement to reconstruct the relevant metabolic pathways of glucose metabolism related to bioenergetics, biosynthesis, and redox homeostasis, and determine differences between frail and non-frail participants, and 2) To identify the most promising biomarkers for a frailty-related energetic signature and plan for a future targeted validation study of diagnostic utility and biological discovery. 

 
3. Project Title: Association between Sleep Deficiency and Frailty: What harms most?
  Leader: Naresh Punjabi, MD, PhD, Jiawei Bai, PhD
 

Epidemiologic surveys show that at least 50% of adults over 65 years in age have sleep-related complaints. Sleep disturbance has been associated with neurohormonal, circadian, and homeostatic alterations: As many such changes have been evidenced by this OAIC and others to also underlie frailty, it reasonable to expect interconnections between sleep quality and frailty. We hypothesize that disordered sleep heightens risk for frailty onset and believe that intervention to improve sleep can prevent or buffer frailty. Prior studies indicate that poor sleep quality is associated with frailty. These predominantly have assessed sleep, however, by either self-report or relatively crude summaries (e.g. time in sleep states) of actigraphy or polysomnography data. This project uses data from the community-based Sleep Heart Health Study (SHHS) to extract power spectral “curves” summarizing the history of the overnight sleep EEG, by functional principal components analysis (fPCA), and identify sleep EEG signatures highly associated with frailty prevalence, incidence and transitions, and vice versa. 

 
4. Project Title: PCSK9 Links Age and Frailty Inflammation to Endothelial Cell Dysfunction
  Leader: Thorsten Leucker, MD, PhD, Gary Gerstenblith, MD.
 

One of the most significant aspects of aging is the marked increase in mortality and significant lifelong disability due to coronary vascular and cerebrovascular disease respectively. There is heterogeneity in that risk with a significant increase in older individuals with frailty and those with the prediabetes, both of which are increased with age and independently associated with vascular disease. Many preclinical and clinical studies indicate that inflammation is a common predisposing factor but the link between inflammation and vascular disease in older adults and particularly in those with frailty and pre-diabetes is not well characterized. Decreased endothelial cell (EC) production and release of nitric oxide (NO), which has potent anti-atherosclerotic effects is a driver of the development and progression of atherosclerotic vascular disease. Beyond its role in cholesterol homeostasis, proprotein convertase subtilisin/kexin type 9 (PCSK9, is associated with the future risk of cardiovascular diseases. Laboratory studies of isolated ECs demonstrate that inflammatory stimuli increase EC PCSK9 and, in separate experiments, that increased PCSK9 decreases endothelial nitric oxide synthase (eNOS) and NO bioavailability, decreases which indicate EC dysfunction independent of low-density lipoprotein cholesterol (LDL-C).

 

This research will examine whether PCSK9 links proinflammatory stimuli with EC dysfunction by studying in vivo endothelial- dependent vascular function and in vitro basic studies of ECs. A comparison of the in vivo and in vitro results will also provide information regarding the extent to which vascular dysfunction in the older groups is related to systemic, circulating factors and to mitochondrial dysfunction. In addition to association, we will examine causality by using PCSK9 targeted small interfering RNA in the above basic studies. The significance of the research to the field of aging, therefore, is the opportunity it offers to understand whether EC PCSK9 is one mediator of the known cardiovascular risk associated with inflammation in older individuals, which then would provide a target of intervention as PCSK9 antibodies are available for clinical use.

 
5. Project Title: Daily physical activity patterns and the modifying role of inflammatory markers in frailty
  Leader: Amal Wanigatunga, PhD, MPH, Jennifer A. Schrack, PhD, Lawrence J. Appel, MD, MPH, Dr. Robert H. Christenson, PhD
 

Frailty is a common medical syndrome of increased vulnerability in adults aged 70 years and older that is often accompanied by low daily physical activity (PA) and high chronic inflammation. Currently, the method by which low PA is quantified and defined relies on coarse measures of self-reported time spent in a few daily activities, leaving a large knowledge gap regarding the true manifestation of PA decrements in frailty. Moreover, chronic inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP) have been linked to components of frailty, including high fatigability and functional decline, making it plausible that degradation of daily PA patterns may be connected to rising circulation of both IL-6 and CRP. This warrants further investigation into inflammation as a possible underlying mechanism connecting detailed measures of PA and the onset and progression of frailty with aging. Findings from such investigation would lay the groundwork towards building the clinical utility of measuring physical activity in non-laboratory, community-dwelling settings to detect and intervene on trajectories towards frailty and accelerated aging in ever-expanding older adult populations.

 

The proposed research aims to examine (1) whether total daily PA and patterns of daily PA accumulation differ by frailty status (non-frail, pre-frail, and frail), and (2) whether chronic inflammation modifies this association. We hypothesize that free-living PA patterns are deteriorated and diminished in those who exhibit pre-frail and frail phenotypes, compared to non-frail individuals. Further, we hypothesize that these sophisticated measures of PA are sensitive to rising chronic inflammation (IL-6 and CRP) typically present in frail older adults. The proposed research provides an exciting opportunity to use cutting-edge methods to extract unique patterns of PA accumulation from objectively measured PA and assess whether greater deterioration in these PA patterns are seen with higher inflammation and frailty states. 

 
DEVELOPMENT PROJECTS (3 Development Projects Listed)
1. Project Title: Characterizing Longitudinal Interdependence among Multiple Multi-System Dysregulation (MSD) Biomarkers
  Leader: Karen Bandeen-Roche, PhD
  Core(s):
 

MSD has long been hypothesized as a determinant of frailty but rarely has been assessed other than through counts of dysregulated systems taken cross-sectionally. This DP lays groundwork for its study as a dynamic process through specific aims to: (1) Characterize longitudinal interdependence among biomarkers of systems thought to underlie frailty; (2) Derive summary measures of longitudinal dysregulation in multiple systems; (3) Validate measures resulting from (2) by assessing their associations with frailty and mortality, and whether they are stronger predictors of frailty than the count measure.  

 
2. Project Title: Development of an aptamer to selectively target the angiotensin autoantibody
  Leader: Peter Abadir, MD, Neal Fedarko, PhD
  Core(s):
 

Prior RC-2 studies have focused on the angiotensin system as a potential contributor to frailty and as a target for intervention development. A recent publication in part supported by RC-1, 2, and 3 described agonistic autoantibodies (aAbs) against the Angiotensin Type 1 Receptor (AT1R) whose serum levels increased in older
adults and were associated with inflammatory cytokines, hypertension, adverse health outcomes and frailty. Aptamers are oligonucleotides that bind their targets with high affinity and specificity and are currently used for
in vitro diagnostics, biosensor technologies, and targeted therapies. RNA aptamer agents can be engineered as allosterically modulated ribozymes - where binding to the targeted aAb activates the selfcleaving ribozyme domain and a fluorescence quencher is removed, yielding a fluorescent signal. This DP seeks to develop the lead agents necessary for creating a unique high throughput diagnostic/prognostic quantitative assay.  

 
3. Project Title: Development and Validation of Age-, Sex-, and Race-specific Thresholds for the Physical Frailty Phenotype Criteria Among Kidney Transplant Candidates and Recipients
  Leader: Nadia M. Chu, PhD
  Core(s):
 

The physical frailty phenotype (PFP) is a measure of frailty recognized for its clinical utility. Frailty, based on the current PFP criteria, is common and associated with adverse outcomes among adult kidney transplant (KT) candidates and recipients. However, older and African American candidates/recipients are disproportionately impacted by frailty. Despite differences found between age and racial subgroups in KT, recent studies in community-dwelling older adults suggest that these variations may be partially due to measurement error, such that PFP criteria may assess frailty differentially between subgroups, resulting in potential misclassification. Given that KT populations comprise of a wider age-range and a greater prevalence of males and minority groups, this potential misclassification of individuals as frail could make it especially challenging for clinicians to identify candidates that can withstand surgery and benefit from KT. Our overall goal for this study will be to generate age-, sex-, and race-specific PFP criteria thresholds for KT candidates and recipients by leveraging an ongoing, prospective, multi-center NIA-funded R01 on frailty and aging in ESRD of 7,803 candidates and 1,383 recipients (aged ?18) linked to the national registry of all KT candidates and recipients. Specifically, we will aim to (1) test if age-, sex-, and race-specific thresholds for PFP criteria are needed among KT candidates and recipients; (2) calculate nationally-representative thresholds for continuous PFP components among KT candidates and recipients and create an updated PFP; and (3) compare predictive validity of the original PFP and the updated PFP (incorporating new nationally-representative thresholds) against adverse outcomes including waitlist mortality, longer length of stay, graft loss and post-KT mortality. Linkage to the national registry provides the unique opportunity to translate measures that were collected at the cohort-level and project them to the national-level in order to calculate nationally-representative thresholds for the PFP criteria using creative statistical methodologies. By doing so, we will reduce misclassification in future studies examining predictors, mechanisms, and consequences of frailty, which can have a direct impact on clinical practice by improving risk stratification, identifying frail candidates for prehabilitation, and improving equitable access to KT, particularly for older, robust candidates. Findings from this study will support the American Society of Transplantation’s goal to establish a standard, validated measure of frailty in solid organ transplantation. Additionally, with expert guidance from the OAIC Biostatistics Core, study findings will provide a benchmark for the operationalization of frailty and a blueprint for gerontologists on how to identify appropriate thresholds to improve geriatric assessments.  

 
RESEARCH (72 Projects Listed)
1. Project Title: AGING-RELATED BIODEMOGRAPHY OF LIFE COURSE PHYSIOLOGY AND ENVIRONMENTAL MODIFIERS
  Leader(s): SEPLAKI, CHRISTOPHER
    UNIVERSITY OF ROCHESTER
    NIH K01AG031332 / (2009-2014)
  Core(s):
  DESCRIPTION (provided by applicant): New integrative biodemographic and gerontological frameworks, a better etiologic understanding of both disease and geriatric conditions, and technological advances in minimally-invasive specimen collection are resulting in the incorporation of increasingly broad arrays of biological markers into population research. This career award will draw on these advanc...
 
2. Project Title: FRAILTY AND ADVERSE HEALTH OUTCOMES OF AGING IN OLDER ADULTS WITH KIDNEY FAILURE
  Leader(s): MCADAMS DEMARCO, MARA A.
    THE JOHNS HOPKINS UNIVERSITY
    NIH K01AG043501 / (2013-2018)
  Core(s):
  DESCRIPTION (provided by applicant): There are >400,000 older ESRD patients in the United States; adults over 55 are the fastest growing age group, and also the most challenging to treat and counsel. In older ESRD patients, risk prediction for patients undergoing the 2 available treatment modalities -- dialysis and kidney transplantation (KT) -- is based on generic metrics derived from national re...
 
3. Project Title: INTERSECTION OF PHYSIOLOGIC FRAILTY AND COGNITIVE PERFORMANCE IN OLDER ADULTS: AN INTEGRATIVE DATA ANALYSIS
  Leader(s): GROSS, ALDEN L.
    THE JOHNS HOPKINS UNIVERSITY
    NIH K01AG050699 / (2016-2021)
  Core(s):
  DESCRIPTION (provided by applicant): Alden L. Gross is an Assistant Professor in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health. He seeks a mentored career development award to obtain critical knowledge skills in the biology of aging, particularly as it relates to frailty in older adults, and necessary research experience foran independent career a...
 
4. Project Title: VISION LOSS AND COGNITION: TESTING THE SENSORY CONSEQUENCE HYPOTHESIS
  Leader(s): SWENOR, BONNIELIN
    THE JOHNS HOPKINS UNIVERSITY
    NIH K01AG052640 / (2017-2022)
  Core(s):
  ABSTRACTThis is an application for a K01 Research Career Development Award. The goal of the proposed project is toprovide the candidate with advanced skills needed to establish an independent research program examiningthe relationship between vision loss and cognitive decline in older individuals. To facilitate this long-term goalthe candidate will: (1) characterize the longitudinal relationship b...
 
5. Project Title: ALTERATION OF KYNURENINE PATHWAY IN AGE-ASSOCIATED MUSCLE WEAKNESS
  Leader(s): CHUNG, TAE HWAN
    THE JOHNS HOPKINS UNIVERSITY
    NIH K08AG058483 / (2018-2023)
  Core(s):
  PROJECT SUMMARY Decline in skeletal muscle function with aging is a major determinant of disability and morbidity in late life.However, the neurobiology of such decline in skeletal muscle function in normal aging is poorly understood.The proposed K08 project is a critical step towards to understanding the underlying mechanism of age-relateddecline of skeletal muscle function. This study uniquely f...
 
6. Project Title: VACCINE-INDUCED IMMUNITY AGAINST INFLUENZA IN FRAILTY
  Leader(s): LENG, SEAN XIAO
    THE JOHNS HOPKINS UNIVERSITY
    NIH K23AG028963 / (2006-2011)
  Core(s):
  DESCRIPTION (provided by applicant): Sean Leng, MD PhD, has demonstrated great promise, and unsurpassed determination, to become a leader in clinical / translational aging research. He has had advanced training in Immunology and Molecular Virology, Cytokine Research, and Internal Medicine. After a clinical and research fellowship in Geriatric Medicine and Gerontology at Johns Hopkins, he was rec...
 
7. Project Title: ACCESS TO KIDNEY TRANSPLANTATION IN ELDERLY PATIENTS
  Leader(s): SEGEV, DORRY L
    THE JOHNS HOPKINS UNIVERSITY
    NIH K23AG032885 / (2009-2012)
  Core(s):
  DESCRIPTION (provided by applicant): Dr. Dorry Segev is a junior faculty member in Transplant Surgery at the Johns Hopkins School of Medicine, where he received all of his medical education and training. He is also completed all requirements for an MHS in Biostatistics and is pursuing a PhD in Clinical Investigation from the Johns Hopkins Bloomberg School of Public Health. Dr. Segev's previous w...
 
8. Project Title: TREATMENT BURDEN IN OLDER ADULTS WITH DIABETES AND MULTIMORBIDITY
  Leader(s): BOYD, CYNTHIA MELINDA
    THE JOHNS HOPKINS UNIVERSITY
    NIH K23AG032910 / (2009-2014)
  Core(s):
  The increasing prevalence of chronic disease in the aging U.S. population presents substantial challenges todelivering medical care that is both patient-centered and consistent with evidence-based guidelines. Dr.Boyd's prior work demonstrated that the application of disease-specific guidelines to older patients withmultimorbidity is limited by the complexity, expense, and burden ofthe recommended ...
 
9. Project Title: CMV INFECTION AND T-CELL RECEPTOR DIVERSITY IN THE PATHOGENESIS OF FRAILTY
  Leader(s): WANG, GEORGE C.
    THE JOHNS HOPKINS UNIVERSITY
    NIH K23AG033113 / (2010-2012)
  Core(s):
  Project Summary/Abstract George C. Wang, MD, is an Instructor of Medicine in the Division of Geriatric Medicine at the JohnsHopkins University School of Medicine. His long-term career goal, as an independent clinical investigator, is toadvance the understanding of the aging immune system and improve older adults' quality of life throughimproved vaccination and immunotherapeutic strategies. During ...
 
10. Project Title: AGE RELATED CHANGE IN ANGIOTENSIN RECEPTORS AND ITS ROLE IN CHRONIC INFLAMMATION
  Leader(s): ABADIR, PETER M.
    THE JOHNS HOPKINS UNIVERSITY
    NIH K23AG035005 / (2010-2016)
  Core(s):
  Project Abstract:Aging is associated with enhanced inflammation. An altered ratio between angiotensin receptors AT1R andAT2R results in induction of inflammation in animal models. The effects of aging on the expression of AT1R andAT2R in humans and the contribution of changes in AT1R and AT2R to increased inflammation in the older havenot been previously studied. Our preliminary evidence suggests ...
 
11. Project Title: PREVENTION AND COGNITIVE CONSEQUENCES OF POSTOPERATIVE DELIRIUM
  Leader(s): BROWN, CHARLES HUGH
    THE JOHNS HOPKINS UNIVERSITY
    NIH K23AG051783 / (2017-2017)
  Core(s):
  PROJECT SUMMARY/ABSTRACTBackground: Among older adults, delirium, cognitive decline, and functional decline after surgery arecommon. These issues may be particularly important in spine surgery patients, in whom my GEMSSTARstudy showed a 43% incidence of delirium. In this proposal, I will build the foundation for a research careerfocused on reducing neurocognitive and functional decline after surge...
 
12. Project Title: ASSOCIATION OF FRAILITY WITH POST THYROIDECTOMY ALTERATIONS IN VOICE, SWALLOWING, AND QUALITY OF LIFE
  Leader(s): MATHUR, AARTI
    THE JOHNS HOPKINS UNIVERSITY
    NIH K23AG053429 / (2017-2022)
  Core(s):
  Project SummaryThis project aims to evaluate the association of frailty with post-operative changes in voice, swallowing, andquality of life following thyroidectomy in older adults. Specifically, Aim 1 is to evaluate the effect ofthyroidectomy on voice, swallowing, and quality of life in older adults. The literature suggests that thesealterations occur at a relatively high frequency in younger pat...
 
13. Project Title: DETERMINANTS AND CONSEQUENCES OF FRAILTY AMONG AGING HIV-INFECTED PERSONS
  Leader(s): PIGGOTT, DAMANI
    THE JOHNS HOPKINS UNIVERSITY
    NIH K23AI108357 / (2013-2019)
  Core(s):
  DESCRIPTION (provided by applicant): My career goal is to improve health outcomes for aging HIV-infected and at risk communities and to support the development of health promoting interventions tailored to socially marginalized, resource-constrained, and clinically vulnerable members of these communities. Frailty is an important age-related state of increased vulnerability to stressors that result...
 
14. Project Title: HEARING LOSS AND AGING
  Leader(s): LIN, FRANK R
    THE JOHNS HOPKINS UNIVERSITY
    NIH K23DC011279 / (2010-2016)
  Core(s):
  DESCRIPTION (provided by applicant): Dr. Frank Lin is a junior faculty member in the Department of Otolaryngology-Head & Neck Surgery at the Johns Hopkins School of Medicine where his clinical practice is dedicated to hearing loss and otology. He previously completed a Ph.D in Clinical Investigation at the Johns Hopkins Bloomberg School of Public Health where he applied conceptual models of functi...
 
15. Project Title: AGE-RELATED CHANGES IN THE VESTIBULAR SYSTEM AND FUNCTIONAL IMPLICATIONS
  Leader(s): AGRAWAL, YURI
    THE JOHNS HOPKINS UNIVERSITY
    NIH K23DC013056 / (2014-2019)
  Core(s):
  DESCRIPTION (provided by applicant): This project aims to characterize age-related changes in vestibular function, and explore their influence on important gait outcomes that increase fall risk and mortality in older individuals. These aims will be carried out within the Baltimore Longitudinal Study of Aging (BLSA), a rigorous, comprehensive longitudinal study of >1000 individuals age 20-103. Spec...
 
16. Project Title: GLUCOSE INSULIN AND MUSCLE LOSS
  Leader(s): KALYANI, RITA R
    THE JOHNS HOPKINS UNIVERSITY
    NIH K23DK093583 / (2012-2017)
  Core(s):
  DESCRIPTION (provided by applicant): Dr. Rita Kalyani is a junior faculty member in the Division of Endocrinology and Metabolism at the Johns Hopkins School of Medicine where her clinical practice is dedicated to the prevention and treatment of diabetes. She previously completed a Masters of Health Science in Clinical Investigation at the Johns Hopkins School of Public Health where she applied her...
 
17. Project Title: PATIENT-CENTERED CARE FOR OLDER ADULTS WITH MULTIPLE CHRONIC CONDITIONS: RESEARCH AND MENTORING PROGRAM
  Leader(s): BOYD, CYNTHIA MELINDA
    THE JOHNS HOPKINS UNIVERSITY
    NIH K24AG056578 / (2017-2022)
  Core(s):
  Project SummaryThe aims of this proposal are to 1) develop the candidate's capacity for research, leadership, and mentorshipthrough career development in clinical trials, building and leading national collaborations, and mentoring, 2) toexpand her mentorship of promising junior investigators in patient-oriented aging research, and 3) to pursue aninnovative research direction to develop and evaluat...
 
18. Project Title: MONITORING CEREBRAL AUTOREGULATION IN PATIENTS UNDERGOING TRAUMATIC HIP FRACTURE SURGERY TO IMPROVE POSTOPERATIVE OUTCOMES
  Leader(s): BROWN, CHARLES HUGH
    THE JOHNS HOPKINS UNIVERSITY
    NIH K76AG057020 / (2017-2021)
  Core(s):
  PROJECT SUMMARY/ABSTRACTBackground: Surgery for hip fracture can be devastating for older adults, with complications includingdelirium, increased risk of dementia, and inability to walk. As an anesthesiologist and clinician-scientist, I havefocused on reducing delirium after surgery. In this proposal, I will build the foundation for a research careerfocused on the broader goals of reducing neuroco...
 
19. Project Title: IMPROVING CANCER SCREENING IN OLDER ADULTS WITH LIMITED LIFE EXPECTANCY
  Leader(s): SCHOENBORN, NANCY
    THE JOHNS HOPKINS UNIVERSITY
    NIH K76AG059984 / (2018-2022)
  Core(s):
  PROJECT SUMMARYBackground: Cancer screening can lower cancer-related mortality and morbidity but may be associated withsignificant harms and burdens in older adults. There is often a lag-time of 10 years before patients screenedfor breast, colorectal, or prostate cancers actually benefit. On the other hand, multiple harms from screeningcan occur in the short-term. Older adults with limited life ex...
 
20. Project Title: THE JOHNS HOPKINS ALZHEIMER'S DISEASE RESOURCE CENTER FOR MINORITY AGING RESEARCH
  Leader(s): REBOK, GEORGE W.; THORPE, ROLAND J ;
    THE JOHNS HOPKINS UNIVERSITY
    NIH P30AG059298 / (2018-2023)
  Core(s):
  The Schools of Medicine, Nursing, and Public Health of the Johns Hopkins University areproposing a new Alzheimer's-related Resources Center for Minority Aging Research (AD-RCMAR) in response to RFA-AG-18-002. The aims of this application are to: (1) mentor early-stage investigators from underrepresented backgrounds in minority aging and health disparitiesresearch, with a focus on Alzheimer's disea...
 
21. Project Title: TGFB MODULATION: THERAPEUTIC TARGETING FOR COPD-EMPHYSEMA
  Leader(s): NEPTUNE, ENID R
    THE JOHNS HOPKINS UNIVERSITY
    NIH P50HL107190 / (2011-2015)
  Core(s):
  DESCRIPTION (provided by applicant): COPD is a complex lung disorder with distinct compartmental manifestations which challenge simplistic notions of single gene or single pathway causality. Whereas the airway findings of subepithelial fibrosis and fibroblast proliferation seem to reflect exuberant matrix deposition, the airspace findings of septal loss and cellular apoptosis conversely suggest ma...
 
22. Project Title: OXIDATIVE STRESS AND THE PATHOGENESIS OF SARCOPENIA AND DISABILITY IN OLDER WOMEN
  Leader(s): SEMBA, RICHARD D
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG027012 / (2005-2019)
  Core(s):
  DESCRIPTION (provided by applicant): Disability threatens the independence of many older adults and results in substantial late-life health care needs and associated expenditures. Sarcopenia plays a central role in disability. Our long-term goals are to gain insight into the processes that underlie the development of sarcopenia and disability and to identify possible strategies for prev...
 
23. Project Title: NFKB RELATED GENETIC INFLUENCES ON INFLAMMATION AND POOR HEALTH IN OLDER ADULTS
  Leader(s): WALSTON, JEREMY DAVID
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG027236 / (2006-2011)
  Core(s):
  DESCRIPTION (provided by applicant): The long-term goal of this study is to identify genes and biologic pathways related to inflammation that influence the rapid decline in function and influence frailty and mortality in a subset of older adults. Inappropriate activation of the pro-inflammatory protein NFkB acts as an important gateway in this process. We have identified a cluster of inflammator...
 
24. Project Title: HEPCIDIN AND THE PATHOGENESIS OF ANEMIA IN OLDER ADULTS.
  Leader(s): SEMBA, RICHARD D
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG029148 / (2007-2012)
  Core(s):
  DESCRIPTION (provided by applicant): Anemia is common in older adults and is associated with a wide spectrum of adverse outcomes, including reduced quality of life, weakness, fatigue, disability, and increased mortality. Anemia among older adults is caused by renal failure, chronic inflammation, and nutritional deficiencies, and about one-third of the anemia is unexplained. Hepcidin, a recently ...
 
25. Project Title: THE ROLE AND GENETIC MECHANISM OF EPIGENETIC PLASTICITY IN AGE-RELATED DISEASE
  Leader(s): FEINBERG, ANDREW P.; FALLIN, M DANIELE ;
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG042187 / (2011-2017)
  Core(s):
  Age-related susceptibility to disease is the most common cause of morbidity, mortality, and diminishedquality of life. Although likely related to both genetics and epigenetics, the epigenetic influences on age-related disease have not been defined previously or related to genetic variation. We have recentlyproposed a novel paradigm for understanding the relationship between variation in DNA sequen...
 
26. Project Title: FRAILTY AND RISK PREDICTION IN OLDER ADULTS CONSIDERING KIDNEY TRANSPLANTATION
  Leader(s): SEGEV, DORRY L
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG042504 / (2013-2019)
  Core(s):
  DESCRIPTION (provided by applicant): End stage renal disease (ESRD) disproportionately affects older adults: approximately 60% of dialysis patients are aged e55. On average, older patients who undergo kidney transplantation (KT) have a survival benefit over dialysis. However, referral for KT in older patients is much lower than for other age groups, at almost 1/7th the rate of referral for younger...
 
27. Project Title: AGE RELATED CHANGE IN MITOCHONDRIAL ANGIOTENSIN SYSTEM AND MITOCHONDRIAL DECLINE
  Leader(s): ABADIR, PETER M.
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG046441 / (2014-2019)
  Core(s):
  DESCRIPTION (provided by applicant): Aging and decline in mitochondrial function are closely linked. Key signs of mitochondrial dysfunction include increased generation of reactive oxygen species, fewer ATP molecules produced per O2 consumed, and increased apoptosis. The reduction in ATP translates to lower energy for cellular maintenance processes including mitobiogenesis and turnover. We recentl...
 
28. Project Title: SPHINGOLIPIDS AND INFLAMMATION IN THE DEVELOPMENT AND PROGRESSION OF ALZHEIMER'S
  Leader(s): MIELKE, MICHELLE M
    MAYO CLINIC
    NIH R01AG049704 / (2015-2019)
  Core(s):
  DESCRIPTION (provided by applicant): The pathophysiological brain changes associated with Alzheimer's disease [AD] begin decades before clinical symptoms. Although recent advances have led to a preclinical biomarker model of AD pathogenesis (first amyloid-beta [A ] pathology, second neurodegeneration, and lastly cognitive symptoms), the mechanisms that underlie these pathological change...
 
29. Project Title: ENHANCING MOBILITY IN OLDER ADULTS BY TREATING CHRONIC INFLAMMATION
  Leader(s): WALSTON, JEREMY DAVID
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG050560 / (2016-2019)
  Core(s):
  DESCRIPTION (provided by applicant): Chronic inflammation (CI) as defined by chronic elevation in serum inflammatory markers such as C-reactive protein (CRP) and Interleukin-6 (IL-6) is a known risk for the development of adverse health outcomes in older adults, including mortality, frailty, chronic disease, and mobility declines. Despite this, little is known about howbest to measure C...
 
30. Project Title: NEIGHBORHOODS, COGNITIVE AGING AND MODIFIABLE RISK FACTORS
  Leader(s): CARLSON, MICHELLE C
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG055404 / (2018-2022)
  Core(s):
  The role of modifiable risk factors (RF), like physical activity (PA), sleep quality, social engagement, andcardiovascular (CV) risk is receiving greater attention to promote the cognitive health of an aging populationand reduce risk of Alzheimer's disease. Each of these risk factors is known to be influenced by environmentalsources, such as neighborhood walkability, safety, noise, and access to l...
 
31. Project Title: AGING, COGNITION, AND HEARING EVALUATION IN ELDERS (ACHIEVE) RANDOMIZED TRIAL
  Leader(s): LIN, FRANK R; CORESH, JOSEF ;
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG055426 / (2017-2022)
  Core(s):
  Novel approaches to reduce the risk of age-related cognitive decline, Alzheimer s disease (AD), and otherdementias in older adults are urgently needed given the aging of the population. Epidemiologic studiesdemonstrate that peripheral hearing loss in older adults is strongly and independently associated withaccelerated cognitive decline and incident dementia. Hypothesized mechanistic pathways unde...
 
32. Project Title: ESRD-SPECIFIC PHYSIOLOGIC RESERVE: IMPROVING GERIATRIC TRANSPLANT PROGNOSTICATION - DIVERSITY SUPPLEMENT
  Leader(s): MCADAMS DEMARCO, MARA A.
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG055781 / (2017-2022)
  Core(s):
  Older adults with end stage renal disease (ESRD) who receive kidney transplantation (KT) double their lifeexpectancy. The new kidney allocation system, designed to better match longevity of recipients and allografts,has been in effect for 2 years. During this time, access to KT among older adults has plummeted; with ratesdeclining 10% for candidates aged 61-70 and 24% for those aged >70. The core ...
 
33. Project Title: DOES VESTIBULAR LOSS PREDICT FALLS IN PATIENTS WITH ALZHEIMER'S DISEASE?
  Leader(s): AGRAWAL, YURI
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG057667 / (2018-2023)
  Core(s):
  Project summaryThis project investigates whether vestibular loss predicts falls in patients with Alzheimer s disease (AD).The proposed research is an observational study of 150 patients with AD to evaluate the associationbetween baseline vestibular function and 2-year incidence of falls. We will also explore whether vestibularfunction is associated with balance and gait function, as well as spatia...
 
34. Project Title: FRAILTY, HIV INFECTION, INJECTION DRUG USE AND THE INFLAMMATORY-MICROBIOME
  Leader(s): PIGGOTT, DAMANI
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG060825 / (2018-2023)
  Core(s):
  PROJECT SUMMARY/ABSTRACTWith effective antiretroviral therapy (ART), life expectancy for HIV-infected persons has markedly improved, yetmarked deficits in survival remain for HIV-infected persons with a history of injecting drugs (PWID). Disparitiesamong PWID have been attributed in part to a shifting spectrum of disease to aging-associated conditionsdriven by persistent inflammation even with ART...
 
35. Project Title: CONTRIBUTION OF SENSORIMOTOR FUNCTION TO RISK AND PATHOGENIC MECHANISMS OF ALZHEIMER'S DISEASE AND RELATED DEMENTIAS
  Leader(s): SCHRACK, JENNIFER ANN; AGRAWAL, YURI ; LIN, FRANK R ;
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG061786 / (2019-2023)
  Core(s):
  PROJECT SUMMARYAlzheimer's disease (AD) is the most common cause of dementia. Underlying pathological and physiologicalchanges related to the onset and progression of AD are believed to emerge several years prior to clinicalmanifestations. Sensory impairments, gait abnormalities, and motor slowing may precede the diagnosis of ADby a decade or more, presenting the exciting possibility that changes ...
 
36. Project Title: MITOCHONDRIAL ENERGETICS, EXERCISE INTOLERANCE AND FATIGABILITY IN OLDER PEOPLE WITH HIV
  Leader(s): WEISS, ROBERT G
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AG063661 / (2019-2024)
  Core(s):
  People living with HIV infection (PLWH) are living longer but with advancing age experienceaccelerated functional decline (decreased strength, slowed gait, reduced exercise tolerance) and increasedfrailty, as compared to non-infected individuals. The syndromes of functional decline and frailty are associatedwith impaired quality of life, increased vulnerability to superimposed stresses, and the li...
 
37. Project Title: INFLUENZA VACCINE FAILURE IN ADULTS OVER AGE 75: ROLE OF CHRONIC CMV INFECTION
  Leader(s): LENG, SEAN XIAO
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01AI108907 / (2014-2019)
  Core(s):
  DESCRIPTION (provided by applicant): Seasonal influenza causes significant morbidity and mortality. Annual immunization with a trivalent inactivated vaccine (TIV) is recommended. However, despite improved vaccination coverage in older adults over time, influenza-related mortality has actually increased. While many TIV studies indicate its benefit for older adults as awhole, these studies lacked re...
 
38. Project Title: MECHANISMS OF ANEMIA OF CHRONIC INFLAMMATION AND AGING IN MICE.
  Leader(s): ROY, CINDY NORENE
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01DK082722 / (2009-2014)
  Core(s):
  Abstract:Anemia of inflammation or chronic disease (AICD) is the most common form of anemia in North Americaoutside of iron deficiency (PAS-08-019). Furthermore, the anemia associated with aging and the geriatricsyndrome, frailty has recently been linked to inflammation, suggesting the molecular mechanisms underlyingboth of these anemias may be conserved. Though AICD can arise in diverse clinical ...
 
39. Project Title: HEMODIALYSIS-BASED INTERVENTIONS TO PRESERVE COGNITIVE FUNCTION
  Leader(s): MCADAMS DEMARCO, MARA A.
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01DK114074 / (2018-2022)
  Core(s):
  ABSTRACTOver 640,000 US adults suffer from ESRD, >95% of whom receive hemodialysis (HD) for the rest of their life oruntil transplantation. Kidney disease and HD significantly impact cognitive function, especially higher-orderexecutive function. Only 13% of HD patients have normal cognition; HD patients experience executive functionimpairment at a rate 3-fold higher than the general population, le...
 
40. Project Title: DEVELOPING PERSONALIZED IMMUNOSUPPRESSION FOR OLDER KIDNEY TRANSPLANT RECIPIENTS
  Leader(s): MCADAMS DEMARCO, MARA A.
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01DK120518 / (2018-2022)
  Core(s):
  ABSTRACT>400,000 older adults (age =55) suffer from end-stage renal disease (ESRD). There has been a 5-foldincrease in the number of kidney transplants (KT) in this age group. Older recipients are a distinct group due toimpaired homeostasis, higher comorbidity burden, and immune system attenuation. These physiologic factorsinfluence older KT recipients response to immunosuppression (IS) medicatio...
 
41. Project Title: SLEEP APNEA AND DYSREGULATION OF LIPID METABOLISM
  Leader(s): POLOTSKY, VSEVOLOD Y
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01HL080105 / (2005-2016)
  Core(s):
  Obstructive sleep apnea (OSA) leads to high cardiovascular mortality, which has been attributed tometabolic abnormalities induced by chronic intermittent hypoxia (IH). We have developed a mouse modelof chronic IH, which mimics the oxygen profile in human OSA, and have shown that IH causesdyslipidemia, hepatic steatosis and insulin resistance. We have also shown that IH leads to metabolicdysfunctio...
 
42. Project Title: THE ROLE OF HEPATOCYTE GROWTH FACTOR SIGNALING AIRSPACE HOMEOSTASIS
  Leader(s): NEPTUNE, ENID R
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01HL085312 / (2007-2015)
  Core(s):
  DESCRIPTION (provided by applicant): The most vital function of the lung is gas-exchange. The site of this critical function, the alveolus, must harbor robust mechanisms for both the maintenance and survival of resident cells and the preservation of functional morphology. When these mechanisms are compromised, diseases such as chronic obstructive pulmonary disease, bronchopulmonary dysplasia an...
 
43. Project Title: SLEEP APNEA AND LONGITUDINAL CHANGES IN GLYCEMIA AND INFLAMMATION IN OLDER MEN
  Leader(s): PUNJABI, NARESH M
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01HL089467 / (2008-2013)
  Core(s):
  DESCRIPTION (provided by applicant): Though long part of our common wisdom, the fact that inadequate sleep quantity and quality lead to serious health implications have only recently come under scientific scrutiny. Many of the findings have been striking and frightful. Most germane, it is now evident that normal sleep and health are intimately related. People who sleep less or have sleep-disorde...
 
44. Project Title: FUNCTIONAL DISSECTION OF THE SUDDEN CARDIAC DEATH ASSOCIATED BAZ2B LOCUS
  Leader(s): ARKING, DAN E
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01HL111267 / (2011-2018)
  Core(s):
  DESCRIPTION (provided by applicant): Despite recent progress in treatment and prevention of coronary heart disease, sudden cardiac death (SCD) remains a major public health problem, with an annual incidence of 180,000-250,000 in the U.S. The vast majority of SCD events occur in the general population, with up to 50% of individuals experiencing SCD as a first sign of disease. The critical importa...
 
45. Project Title: MITOCHONDRIAL DNA COPY NUMBER AND GENETIC VARIATION IN CORONARY HEART DISEASE
  Leader(s): ARKING, DAN E
    THE JOHNS HOPKINS UNIVERSITY
    NIH R01HL131573 / (2016-2021)
  Core(s):
  DESCRIPTION (provided by applicant): Coronary heart disease (CHD) continues to be a leading cause of mortality and morbidity worldwide. Age-related decline in mitochondrial function is a novel mechanism that may underlie multiple biological changes that increase the risk of atherosclerosis and CHD in the general population. We determined mtDNA copy number (mtDNA-CN) in whole blood, one ...
 
46. Project Title: CLINICAL SIGNIFICANCE OF SHORT-TERM CHANGE AND VARIABILITY OF GRIP STRENGTH
  Leader(s): XUE, QIAN-LI
    THE JOHNS HOPKINS UNIVERSITY
    NIH R03AG041992 / (2012-2015)
  Core(s):
  DESCRIPTION (provided by applicant): Aging is associated with progressive lose of skeletal muscle mass and strength referred to as sarcopenia, a significant risk factor for disability, fraily, and mortality. Epidemiologically, muscle weakness defined based on a single measurement of hand grip strength has repeatedly proven to correlate with subsequent adverse health outcomes, even when measured...
 
47. Project Title: BIG QUESTIONS IN COGNITIVE AGING: AN INTEGRATIVE ANALYSIS APPROACH
  Leader(s): GROSS, ALDEN L.
    THE JOHNS HOPKINS UNIVERSITY
    NIH R03AG045494 / (2013-2014)
  Core(s):
  DESCRIPTION (provided by applicant): The timing and magnitude of age-related cognitive decline, some of the oldest questions in cognitive aging research, remain open questions of major importance. Although many studies have been conducted, we often cannot compare results because they use different cognitive tests and are not directly comparable. The goal of this proposal is to conduct an integrati...
 
48. Project Title: FRAILTY ASSESSMENT: MATCHING SIMPLIFICATION EFFORTS TO CLINICAL AIMS
  Leader(s): XUE, QIAN-LI
    THE JOHNS HOPKINS UNIVERSITY
    NIH R03AG048541 / (2014-2017)
  Core(s):
  DESCRIPTION (provided by applicant): Frailty has been theoretically defined as a clinically recognizable state of increased vulnerability in older adults. Although numerous instruments have been developed to identify frailty, consensus on best measures has not been achieved. The two most commonly cited frailty measures in the geriatric literature are the Physical Frailty Phenotype (PFP) and the ...
 
49. Project Title: LEAN BODY MASS AND THE DEVELOPMENT OF DIABETES
  Leader(s): KALYANI, RITA R
    THE JOHNS HOPKINS UNIVERSITY
    NIH R03DK109163 / (2016-2019)
  Core(s):
  DESCRIPTION (provided by applicant): Given the projected increasing burden of diabetes in the future, understanding modifiable risk factors for its development is important for public health in order to develop appropriate and targeted preventive strategies. While it has been well described that obesity is a risk factor for type 2 diabetes development, critical questions regarding the r...
 
50. Project Title: TISSUE-BASED VALIDATION OF COPD GENETIC STUDIES USING LUNG HEALTH STUDY COHORT
  Leader(s): NEPTUNE, ENID R
    THE JOHNS HOPKINS UNIVERSITY
    NIH R03HL095406 / (2008-2013)
  Core(s):
  DESCRIPTION (provided by applicant): Tissue-based validation of COPD Genetic Studies using Lung Health Study Cohort Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in North America, affecting 10-12 million Americans. Although cigarette smoking is the most common environmental risk factor involved in development of COPD, only 10-20% of heavy smokers ever deve...
 
51. Project Title: DEVELOPMENT OF A MOUSE MODEL FOR FRAILTY
  Leader(s): WALSTON, JEREMY DAVID
    THE JOHNS HOPKINS UNIVERSITY
    NIH R21AG025143 / (2007-2010)
  Core(s):
  DESCRIPTION (provided by applicant): The goal of this study is to establish a frail mouse model that can be utilized in future etiologic and intervention studies of the geriatric syndrome of frailty. The phenotypic characteristics sought in this model include age related declines in activity, muscle strength, and weight, and increased markers systemic inflammation as characterized by increased s...
 
52. Project Title: DEVELOPMENT OF BLOOD LIPID BIOMARKERS FOR ALZHEIMER'S DISEASE PROGRESSION
  Leader(s): MIELKE, MICHELLE M
    THE JOHNS HOPKINS UNIVERSITY
    NIH R21AG028754 / (2007-2010)
  Core(s):
  DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Findings from the literature, and preliminary data reported in this application, suggest lipid measures, including brain-derived cholesterol species and lipid peroxidation products, may produce unique, readily detectable signatures in the blood of AD patients. These signatures may be indica...
 
53. Project Title: EXPLORING FACTORS INFLUENCING GENDER DISPARITIES IN ACCESS TO TRANSPLANTATION
  Leader(s): SEGEV, DORRY L
    THE JOHNS HOPKINS UNIVERSITY
    NIH R21AG034523 / (2010-2013)
  Core(s):
  DESCRIPTION (provided by applicant): In the modern era, kidney transplantation is a safe and effective treatment for many patients with kidney failure. However, choosing the right patients for kidney transplantation is difficult, especially among older patients. Although older patients who receive transplants survive longer than if they had stayed on dialysis, still very few older patients are p...
 
54. Project Title: NOVEL FORMULATION OF TOPICAL LOSARTAN FOR TREATMENT OF WOUNDS IN AGING
  Leader(s): WALSTON, JEREMY DAVID; ABADIR, PETER M. ;
    THE JOHNS HOPKINS UNIVERSITY
    NIH R21AG043284 / (2013-2016)
  Core(s):
  DESCRIPTION (provided by applicant): The development of pressure ulcers is one of the most painful, debilitating, and costly conditions that impact older adults. The increased risk for skin breakdown and poor healing in older adults is both extrinsic (incontinence, immobility) and intrinsic (decreased elasticity, perfusion, and oxygenation). Although improvements in wound care have been made ...
 
55. Project Title: CHRONIC CMV INFECTION IN THE ELDERLY: DIAGNOSIS AND LINK TO CHRONIC INFLAMMATION
  Leader(s): LENG, SEAN XIAO
    THE JOHNS HOPKINS UNIVERSITY
    NIH R21AG043874 / (2013-2016)
  Core(s):
  DESCRIPTION (provided by applicant): A large body of evidence from us and others indicates that a chronic inflammatory state marked by elevated IL-6 contributes to many age-related diseases, frailty, disability and mortality in older adults. Despite this, the causes and underlying mechanisms leading to this chronic inflammatory state remain to be defined. Studies have reported clonal expansion ...
 
56. Project Title: RECOMBINANT HUMAN LACTOFERRIN FOR THE TREATMENT OF CHRONIC INFLAMMATION IN OLDER ADULTS.
  Leader(s): WALSTON, JEREMY DAVID
    THE JOHNS HOPKINS UNIVERSITY
    NIH R21AG053681 / (2016-2019)
  Core(s):
  Project AbstractMild persistent activation of inflammatory pathways, often termed chronic inflammation (CI) is observed in up to30% of older adults. Dozens of population studies have identified significant associations between serum-based pro-inflammatory measures and functional decline, frailty, worsening chronic illness, cognitive decline,mortality and reduced gait speed. Serum markers of CI suc...
 
57. Project Title: MEASUREMENT OF COGNITIVE FUNCTION IN OLDER ADULTS WITH SENSORY LOSS
  Leader(s): SWENOR, BONNIELIN; DEAL, JENNIFER ANNE ;
    THE JOHNS HOPKINS UNIVERSITY
    NIH R21AG060243 / (2019-2021)
  Core(s):
  ABSTRACTThe goal of the proposed project is to determine if estimates of cognitive impairment and Alzheimer s diseaseand related dementias (ADRD) are biased among older adults with hearing or vision impairment. The impact ofthis this potential bias could be significant, as over 55% of Americans 60 years and older have either hearingor vision impairment. The specific aims of this research are to: (...
 
58. Project Title: TREATMENT BURDEN IN COMPLEX OLDER PATIENTS AS A TARGET FOR INTERVENTION
  Leader(s): BOYD, CYNTHIA MELINDA
    THE JOHNS HOPKINS UNIVERSITY
    AHRQ R21HS017650 / (2008-2011)
  Core(s):
  DESCRIPTION (provided by applicant): Complex older patients present substantial challenges to delivering medical care that is both guideline-based and patient-centered. There is little information available to guide a patient with complex health status and his or her physicians when they weigh the risks, burdens and benefits of a test or treatment plan to diagnose or treat chronic diseases. Desp...
 
59. Project Title: IMPROVING CLINICAL PRACTICE GUIDELINES FOR COMPLEX PATIENTS
  Leader(s): BOYD, CYNTHIA MELINDA
    THE JOHNS HOPKINS UNIVERSITY
    AHRQ R21HS018597 / (2009-2012)
  Core(s):
  DESCRIPTION (provided by applicant): Many of the major barriers to applying evidence-based guidelines in complex patients originate from the fact that guidelines are developed for the management of diseases instead of people with diseases. With rare exceptions, guidelines focus on the management of a single disease, or a single disease-problem, and do not address how to optimally integrate care ...
 
60. Project Title: BLOOD-BASED LIPID BIOMARKERS REFLECTIVE OF ALZHEIMER-ASSOCIATED NEURODEGENERATION
  Leader(s): MIELKE, MICHELLE M
    THE JOHNS HOPKINS UNIVERSITY
    NIH R21NS060271 / (2007-2010)
  Core(s):
  DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Findings from the literature, and preliminary data reported in this application, suggest lipid measures, including brain-derived cholesterol species and lipid peroxidation products, may produce readily detectable signatures in the blood of AD patients. These signatures may be indicators of ...
 
61. Project Title: A RANDOMIZED, BLINDED, PLACEBO-CONTROLLED CLINICAL TRIAL TO EVALUATE LONGEVERON MESENCHYMAL STEM CELL (LMSC) THERAPY FOR TREATING THE METABOLIC SYNDROME
  Leader(s): HARE, JOSHUA M; LENG, SEAN XIAO ; OLIVA, ANTHONY ANDREW ;
    LONGEVERON LLC
    NIH R42AG054322 / (2017-2021)
  Core(s):
  The metabolic syndrome (MetS) is a cluster of factors that increases the risks for cardiovascular disease, type 2diabetes mellitus, and mortality, and currently affects > 40% of US adults. MetS is associated with endothelialdysfunction, decreased circulating endothelial progenitor cells (EPCs), and a pro-inflammatory state. We havemade the exciting discovery that therapy with allogeneic mesenchyma...
 
62. Project Title: TRANSITIONS TO FAMILY CAREGIVING AND ITS IMPACT ON HEALTH INDICATORS
  Leader(s): ROTH, DAVID L
    THE JOHNS HOPKINS UNIVERSITY
    NIH RF1AG050609 / (2016-2021)
  Core(s):
  DESCRIPTION (provided by applicant): The growth of the older adult population, increased prevalence of many disabling conditions, and high costs of institutional care are placing heavy demands on family members to provide informal caregiving services to adults with disabilities. Many previous studies have characterized caregiving as a chronic stress experience associated with poorer hea...
 
63. Project Title: REPRODUCTIVE RISK FACTORS FOR ALZHEIMER'S DISEASE DEMENTIA AND PATHOLOGY
  Leader(s): MIELKE, MICHELLE M
    MAYO CLINIC
    NIH RF1AG055151 / (2017-2022)
  Core(s):
  PROJECT SUMMARY/ABSTRACTRecent estimates suggest that almost two-thirds of the individuals diagnosed with Alzheimer s disease [AD]are women. The National Institutes of Health and the Alzheimer s Association have highlighted the critical needto understand sex differences in the risk factors and clinical progression of AD. Reproductive and hormonalfactors may be particularly important for women. Hyp...
 
64. Project Title: LONGITUDINAL STUDY OF LIPIDS AND APOE IN THE DEVELOPMENT OF AD AND AD PATHOLOGY
  Leader(s): MIELKE, MICHELLE M
    MAYO CLINIC
    NIH U01AG037526 / (2011-2015)
  Core(s):
  DESCRIPTION (provided by applicant): The E4 allele of the Apolipoprotein E (ApoE) gene is the strongest genetic risk factor for the onset of sporadic Alzheimer's disease (AD) identified to date. The roles by which ApoE influences amyloid-beta (A2) metabolism and non-A2-mediated mechanisms in AD pathogenesis, however, remain to be fully clarified. The literature, and our preliminary data, suggest...
 
65. Project Title: VITAMIN D SUPPLEMENTS TO PREVENT FALLS IN OLDER ADULTS: A DOSE-RESPONSE TRIAL
  Leader(s): APPEL, LAWRENCE JOHN
    THE JOHNS HOPKINS UNIVERSITY
    NIH U01AG047837 / (2014-2020)
  Core(s):
  DESCRIPTION (provided by applicant): The public health burden of falls in older persons is substantial. Several lines of evidence suggest that vitamin D supplements might substantially reduce the risk of falls, potentially by > 25% in persons with low serum 25-hydroxyvitamin D [25(OH)D] levels. However, trial evidence is insufficient to guide policy. The proposed study is a seamless, two stage, B...
 
66. Project Title: ENERGY RESERVES, PHYSICAL ACTIVITY, AND ALZHEIMER'S DISEASE IN THE BALTIMORE LONGITUDINAL STUDY OF AGING
  Leader(s): SCHRACK, JENNIFER ANN
    THE JOHNS HOPKINS UNIVERSITY
    NIH U01AG057545 / (2017-2022)
  Core(s):
  PROJECT SUMMARYAlzheimer s disease (AD) is the most common cause of dementia. Underlying pathological and physiologicalchanges related to the onset and progression of AD are believed to emerge several years prior to clinicalmanifestations. Gait abnormalities and motor slowing typically precede the diagnosis of AD by a decade ormore, presenting the exciting possibility that changes in gait may act ...
 
67. Project Title: VALIDATION OF NUCLEAR MORPHOLOGY AS A BIOMARKER OF AGING AND AGING-RELATED PHENOTYPES
  Leader(s): WIRTZ, DENIS
    THE JOHNS HOPKINS UNIVERSITY
    NIH U01AG060903 / (2018-2023)
  Core(s):
  AbstractAlterations in the nuclear protein lamin and associated structures in the nucleus have beenidentified as a source of nuclear morphology changes that markedly impact overall cellularfunction. These changes in nuclear morphology are thought to drive molecular changes thatinfluence a wide range of aging-related phenotypes and chronic disease states. Importantly, wehave recently used high-thro...
 
68. Project Title: STRUCTURAL NESTED MODELS FOR ASSESSING THE SAFETY AND EFFECTIVENESS OF GENERIC DRUGS
  Leader(s): VARADHAN, RAVI
    THE JOHNS HOPKINS UNIVERSITY
    FDA U01FD005556 / (2015-2019)
  Core(s):
  Project SummaryThe U.S. Food and Drug Administration (FDA) expects that approved generic products provide the samequality, safety, and efficacy as the corresponding brand. Despite this, some clinicians and patients arereluctant to use generic medications due to fears of lesser effectiveness or concerns about toxicities or sideeffects. The FDA seeks to ensure that patients can confidently access ge...
 
69. Project Title: SLEEP APNEA TREATMENT WITH POSITIVE AIRWAY PRESSURE FOR PREVENTION OF DIABETES MELLITUS
  Leader(s): PUNJABI, NARESH M
    THE JOHNS HOPKINS UNIVERSITY
    NIH U34DK120051 / (2018-2020)
  Core(s):
  ABSTRACTThis application is in response to the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK)program announcement PAR-18-423 for implementing a multi-center randomized clinical trial to test thehypothesis that treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy inpeople with prediabetes will reduce the progression to type 2 diabetes mel...
 
70. Project Title: SEX AND AGE DIFFERENCES IN IMMUNITY TO INFLUENZA (SADII)
  Leader(s): KLEIN, SABRA L.
    THE JOHNS HOPKINS UNIVERSITY
    NIH U54AG062333 / (2018-2023)
  Core(s):
  SEX AND AGE DIFFERENCES IN IMMUNITY TO INFLUENZA (SADII) SUMMARYThe NIH Office of Research on Women s Health (ORWH) should support a Specialized Center of ResearchExcellence (SCORE) on sex differences in influenza immunity because despite having antivirals and vaccines,influenza remains a significant public health threat, causing approximately 100,000 hospitalizations, 30,000deaths, and approximat...
 
71. Project Title: CHARACTERIZING RESILIENCIES TO PHYSICAL STRESSORS IN OLDER ADULTS: A DYNAMICAL PHYSIOLOGICAL SYSTEMS APPROACH
  Leader(s): WALSTON, JEREMY DAVID; BANDEEN-ROCHE, KAREN J. ; VARADHAN, RAVI ;
    THE JOHNS HOPKINS UNIVERSITY
    NIH UH2AG056933 / (2017-2019)
  Core(s):
  Project SummaryWhen confronted with a major physical stressor, some older adults are able to recover, with minimal decline,their physical and cognitive function, while others suffer precipitous, irreversible declines in function. This is thecentral notion behind resiliency. Little is known about the intrinsic (e.g., physiologic and molecular processes)and extrinsic (e.g., health behaviors) factors...
 
72. Project Title: CHARACTERIZING RESILIENCIES TO PHYSICAL STRESSORS IN OLDER ADULTS: A DYNAMICAL PHYSIOLOGICAL SYSTEMS APPROACH
  Leader(s): WALSTON, JEREMY DAVID; BANDEEN-ROCHE, KAREN J. ; VARADHAN, RAVI ;
    THE JOHNS HOPKINS UNIVERSITY
    NIH UH3AG056933 / (2019-2022)
  Core(s):
  Project SummaryWhen confronted with a major physical stressor, some older adults are able to recover, with minimal decline,their physical and cognitive function, while others suffer precipitous, irreversible declines in function. This is thecentral notion behind resiliency. Little is known about the intrinsic (e.g., physiologic and molecular processes)and extrinsic (e.g., health behaviors) factors...
 
PUBLICATIONS
2021
 
2020
  1. Physical Frailty Phenotype Criteria and their Synergistic Association on Cognitive Functioning.
    Chu NM, Bandeen-Roche K, Xue QL, Carlson MC, Sharrett AR, Gross AL
    J Gerontol A Biol Sci Med Sci, 2020 Oct 15
    pii: glaa267. https://doi.org/10.1093/gerona/glaa267 | PMID: 33057609
    Citations: | AltScore: NA
  2. Frailty Prevalence in Younger End-Stage Kidney Disease Patients Undergoing Dialysis and Transplantation.
    Chu NM, Chen X, Norman SP, Fitzpatrick J, Sozio SM, Jaar BG, Frey A, Estrella MM, Xue QL, Parekh RS, Segev DL, McAdams-DeMarco MA
    Am J Nephrol, 2020 Jul 8, 51(7): 501-510
    https://doi.org/10.1159/000508576 | PMID: 32640462 | PMCID: PMC7442041
    Citations: | AltScore: 3.2
  3. Brain Renin-Angiotensin System at the Intersect of Physical and Cognitive Frailty.
    Cosarderelioglu C, Nidadavolu LS, George CJ, Oh ES, Bennett DA, Walston JD, Abadir PM
    Front Neurosci, 2020, 14: 586314
    https://doi.org/10.3389/fnins.2020.586314 | PMID: 33117127 | PMCID: PMC7561440
    Citations: | AltScore: 21.95
  4. Transcatheter Aortic Valve Replacement in Low-Population Density Areas: Assessing Healthcare Access for Older Adults With Severe Aortic Stenosis.
    Damluji AA, Fabbro M 2nd, Epstein RH, Rayer S, Wang Y, Moscucci M, Cohen MG, Carroll JD, Messenger JC, Resar JR, Cohen DJ, Sherwood MW, O'Connor CM, Batchelor W
    Circ Cardiovasc Qual Outcomes, 2020 Aug, 13(8): e006245
    https://doi.org/10.1161/CIRCOUTCOMES.119.006245 | PMID: 32813564 | PMCID: PMC7590951
    Citations: | AltScore: 33.95
  5. U.S. National Profile of Older Adults with Cognitive Impairment Alone, Physical Frailty Alone, and Both.
    Ge ML, Carlson MC, Bandeen-Roche K, Chu NM, Tian J, Kasper JD, Xue QL
    J Am Geriatr Soc, 2020 Dec, 68(12): 2822-2830
    https://doi.org/10.1111/jgs.16769 | PMID: 32860219
    Citations: | AltScore: 8.9
  6. Plasma levels of corticosterone, tumor necrosis factor receptor 1 and interleukin 6 are influenced by age, sex and chronic inflammation in mice treated with acute temperature stress.
    Ge N, Westbrook R, Langdon J, Yang H, Marx R, Abadir P, Xue QL, Walston JD
    Exp Gerontol, 2020 Dec, 142: 111136
    https://doi.org/10.1016/j.exger.2020.111136 | PMID: 33164891 | PMCID: PMC7705815
    Citations: | AltScore: NA
  7. Derivation of a measure of physiological multisystem dysregulation: Results from WHAS and health ABC.
    Gross AL, Carlson MC, Chu NM, McAdams-DeMarco MA, Mungas D, Simonsick EM, Varadhan R, Xue QL, Walston J, Bandeen-Roche K
    Mech Ageing Dev, 2020 May 11, 188: 111258
    https://doi.org/10.1016/j.mad.2020.111258 | PMID: 32423871 | PMCID: PMC7375911
    Citations: | AltScore: 5.05
  8. Clinically Meaningful Change for Physical Performance: Perspectives of the ICFSR Task Force.
    Guralnik J, Bandeen-Roche K, Bhasin SAR, Eremenco S, Landi F, Muscedere J, Perera S, Reginster JY, Woodhouse L, Vellas B
    J Frailty Aging, 2020, 9(1): 9-13
    https://doi.org/10.14283/jfa.2019.33 | PMID: 32150208 | PMCID: PMC7286121
    Citations: 1 | AltScore: 28.7
  9. An overview of frailty in kidney transplantation: measurement, management and future considerations.
    Harhay MN, Rao MK, Woodside KJ, Johansen KL, Lentine KL, Tullius SG, Parsons RF, Alhamad T, Berger J, Cheng XS, Lappin J, Lynch R, Parajuli S, Tan JC, Segev DL, Kaplan B, Kobashigawa J, Dadhania DM, McAdams-DeMarco MA
    Nephrol Dial Transplant, 2020 Jul 1, 35(7): 1099-1112
    https://doi.org/10.1093/ndt/gfaa016 | PMID: 32191296 | PMCID: PMC7417002
    Citations: 2 | AltScore: 40.3
  10. Development and validation of an inflammatory-frailty index for kidney transplantation.
    Haugen CE, Gross A, Chu NM, Norman SP, Brennan DC, Xue QL, Walston J, Segev DL, McAdams-DeMarco M
    J Gerontol A Biol Sci Med Sci, 2020 Jul 3
    pii: glaa167. https://doi.org/10.1093/gerona/glaa167 | PMID: 32619229
    Citations: | AltScore: 1.25
  11. The Association between Frailty and Uncorrected Refractive Error in Older Adults.
    Lee MJ, Varadaraj V, Tian J, Bandeen-Roche K, Swenor BK
    Ophthalmic Epidemiol, 2020 Jun, 27(3): 219-225
    https://doi.org/10.1080/09286586.2020.1716380 | PMID: 31952461 | PMCID: PMC7080595
    Citations: | AltScore: NA
  12. Spinal Anesthesia for Geriatric Lumbar Spine Surgery: A Comparative Case Series.
    Lessing NL, Edwards CC 2nd, Dean CL, Waxter OH, Lin C, Curto RA, Brown CH 4th
    Int J Spine Surg, 2020 Oct, 14(5): 713-721
    https://doi.org/10.14444/7103 | PMID: 33046538 | PMCID: PMC7671447
    Citations: | AltScore: NA
  13. Stable ischemic heart disease: how to keep it that way.
    Leucker TM, Schulman SP, Gerstenblith G
    J Clin Invest, 2020 Mar 2, 130(3): 1055-1057
    https://doi.org/10.1172/JCI135959 | PMID: 31985489 | PMCID: PMC7269554
    Citations: | AltScore: 8.65
  14. Exercise intolerance and rapid skeletal muscle energetic decline in human age-associated frailty.
    Lewsey SC, Weiss K, Sch?r M, Zhang Y, Bottomley PA, Samuel TJ, Xue QL, Steinberg A, Walston JD, Gerstenblith G, Weiss RG
    JCI Insight, 2020 Oct 15, 5(20):
    pii: 141246. https://doi.org/10.1172/jci.insight.141246 | PMID: 32941181 | PMCID: PMC7605538
    Citations: | AltScore: 42.75
  15. Linking early life risk factors to frailty in old age: evidence from the China Health and Retirement Longitudinal Study.
    Li Y, Xue QL, Odden MC, Chen X, Wu C
    Age Ageing, 2020 Feb 27, 49(2): 208-217
    https://doi.org/10.1093/ageing/afz160 | PMID: 31957780 | PMCID: PMC7047816
    Citations: 2 | AltScore: 11.05
  16. Evaluation of mitochondrial DNA copy number estimation techniques.
    Longchamps RJ, Castellani CA, Yang SY, Newcomb CE, Sumpter JA, Lane J, Grove ML, Guallar E, Pankratz N, Taylor KD, Rotter JI, Boerwinkle E, Arking DE
    PLoS One, 2020, 15(1): e0228166
    https://doi.org/10.1371/journal.pone.0228166 | PMID: 32004343 | PMCID: PMC6994099
    Citations: 5 | AltScore: 1.5
  17. Targeted deletion of interleukin-6 in a mouse model of chronic inflammation demonstrates opposing roles in aging: benefit and harm.
    Ma L, Nidadavolu LS, Yang H, Langdon J, Westbrook R, Tsui BMW, Lee TS, Hinson J, Ling S, Marx-Rattner R, Wu Y, Nguyen T, Tan J, Khadeer M, Moaddel R, Le A, Walston JD, Abadir PM
    J Gerontol A Biol Sci Med Sci, 2020 Jun 26
    pii: glaa156. https://doi.org/10.1093/gerona/glaa156 | PMID: 32585682
    Citations: 2 | AltScore: 21.95
  18. IL10 deficiency promotes alveolar enlargement and lymphoid dysmorphogenesis in the aged murine lung.
    Malinina A, Dikeman D, Westbrook R, Moats M, Gidner S, Poonyagariyagorn H, Walston J, Neptune ER
    Aging Cell, 2020 Apr, 19(4): e13130
    https://doi.org/10.1111/acel.13130 | PMID: 32170906 | PMCID: PMC7189990
    Citations: 2 | AltScore: 0.25
  19. Perceptions and Practices Regarding Frailty in Kidney Transplantation: Results of a National Survey.
    McAdams-DeMarco MA, Van Pilsum Rasmussen SE, Chu NM, Agoons D, Parsons RF, Alhamad T, Johansen KL, Tullius SG, Lynch R, Harhay MN, Rao MK, Berger J, Cooper M, Tan JC, Cheng XS, Woodside KJ, Parajuli S, Lentine KL, Kaplan B, Segev DL, Kobashigawa JA, Dadhania D, AST Kidney Pancreas Community of Practice Workgroup.
    Transplantation, 2020 Feb, 104(2): 349-356
    https://doi.org/10.1097/TP.0000000000002779 | PMID: 31343576 | PMCID: PMC6834867
    Citations: 5 | AltScore: 6.4
  20. Functional Outcomes of Frail Patients After Cardiac Surgery: An Observational Study.
    Nakano M, Nomura Y, Suffredini G, Bush B, Tian J, Yamaguchi A, Walston J, Hasan R, Mandal K, Schena S, Hogue CW, Brown CH 4th
    Anesth Analg, 2020 Jun, 130(6): 1534-1544
    https://doi.org/10.1213/ANE.0000000000004786 | PMID: 32384343 | PMCID: PMC7641106
    Citations: 1 | AltScore: NA
  21. Frailty transitions, inflammation and mortality among persons aging with HIV infection and injection drug use.
    Piggott DA, Bandeen-Roche K, Mehta SH, Brown TT, Yang H, Walston JD, Leng SX, Kirk GD
    AIDS, 2020 Apr 13, 34(8): 1217-1225
    https://doi.org/10.1097/QAD.0000000000002527 | PMID: 32287069
    Citations: 1 | AltScore: 5.5
  22. The transition to family caregiving and its effect on biomarkers of inflammation.
    Roth DL, Haley WE, Sheehan OC, Huang J, Rhodes JD, Durda P, Howard VJ, Walston JD, Cushman M
    Proc Natl Acad Sci U S A, 2020 Jul 14, 117(28): 16258-16263
    https://doi.org/10.1073/pnas.2000792117 | PMID: 32581123 | PMCID: PMC7368336
    Citations: | AltScore: 67.6
  23. Visual Impairment and Frailty: Examining an Understudied Relationship.
    Swenor BK, Lee MJ, Tian J, Varadaraj V, Bandeen-Roche K
    J Gerontol A Biol Sci Med Sci, 2020 Feb 14, 75(3): 596-602
    https://doi.org/10.1093/gerona/glz182 | PMID: 31419280 | PMCID: PMC7328203
    Citations: 1 | AltScore: 1
  24. Dissecting the Racial/Ethnic Disparity in Frailty in a Nationally Representative Cohort Study with Respect to Health, Income, and Measurement.
    Usher T, Buta B, Thorpe RJ, Huang J, Samuel LJ, Kasper JD, Bandeen-Roche K
    J Gerontol A Biol Sci Med Sci, 2020 Mar 9
    pii: glaa061. https://doi.org/10.1093/gerona/glaa061 | PMID: 32147727
    Citations: | AltScore: 11.65
  25. Perceptions, Barriers, and Experiences With Successful Aging Before and After Kidney Transplantation: A Focus Group Study.
    Van Pilsum Rasmussen SE, Warsame F, Eno AK, Ying H, Covarrubias K, Haugen CE, Chu NM, Crews DC, Harhay MN, Schoenborn NL, Segev DL, McAdams-DeMarco MA
    Transplantation, 2020 Mar, 104(3): 603-612
    https://doi.org/10.1097/TP.0000000000002848 | PMID: 31283666 | PMCID: PMC6930354
    Citations: | AltScore: 2.7
  26. Association of peripheral inflammatory markers with connectivity in large-scale functional brain networks of non-demented older adults.
    Walker KA, Gross AL, Moghekar AR, Soldan A, Pettigrew C, Hou X, Lu H, Alfini AJ, Bilgel M, Miller MI, Albert MS, Walston J
    Brain Behav Immun, 2020 Jan 11, 87: 388-396
    pii: S0889-1591(19)31061-X. https://doi.org/10.1016/j.bbi.2020.01.006 | PMID: 31935468 | PMCID: PMC7316598
    Citations: | AltScore: 11.25
  27. Kynurenines link chronic inflammation to functional decline and physical frailty.
    Westbrook R, Chung T, Lovett J, Ward C, Joca H, Yang H, Khadeer M, Tian J, Xue QL, Le A, Ferrucci L, Moaddel R, de Cabo R, Hoke A, Walston J, Abadir PM
    JCI Insight, 2020 Aug 20, 5(16):
    pii: 136091. https://doi.org/10.1172/jci.insight.136091 | PMID: 32814718 | PMCID: PMC7455140
    Citations: | AltScore: 34.1
  28. Single-cell morphology encodes metastatic potential.
    Wu PH, Gilkes DM, Phillip JM, Narkar A, Cheng TW, Marchand J, Lee MH, Li R, Wirtz D
    Sci Adv, 2020 Jan, 6(4): eaaw6938
    https://doi.org/10.1126/sciadv.aaw6938 | PMID: 32010778 | PMCID: PMC6976289
    Citations: 2 | AltScore: 64.45
  29. Frailty as an integrative marker of physiological vulnerability in the era of COVID-19.
    Xue QL
    BMC Med, 2020 Oct 23, 18(1): 333
    https://doi.org/10.1186/s12916-020-01809-1 | PMID: 33092582 | PMCID: PMC7581466
    Citations: | AltScore: 4.3
  30. Discrepancy in Frailty Identification: Move Beyond Predictive Validity.
    Xue QL, Tian J, Walston JD, Chaves PHM, Newman AB, Bandeen-Roche K
    J Gerontol A Biol Sci Med Sci, 2020 Jan 20, 75(2): 387-393
    https://doi.org/10.1093/gerona/glz052 | PMID: 30789645 | PMCID: PMC7176056
    Citations: 3 | AltScore: 2.2
  31. Angiotensin II Blood Levels Are Associated with Smaller Hippocampal and Cortical Volumes in Cognitively Normal Older Adults.
    Yasar S, Moored KD, Adam A, Zabel F, Chuang YF, Varma VR, Carlson MC
    J Alzheimers Dis, 2020, 75(2): 521-529
    https://doi.org/10.3233/JAD-200118 | PMID: 32280103 | PMCID: PMC7293768
    Citations: 1 | AltScore: 10
  32. Mitochondrial DNA copy number and incident atrial fibrillation.
    Zhao D, Bartz TM, Sotoodehnia N, Post WS, Heckbert SR, Alonso A, Longchamps RJ, Castellani CA, Hong YS, Rotter JI, Lin HJ, O'Rourke B, Pankratz N, Lane JA, Yang SY, Guallar E, Arking DE
    BMC Med, 2020 Sep 16, 18(1): 246
    https://doi.org/10.1186/s12916-020-01715-6 | PMID: 32933497 | PMCID: PMC7493408
    Citations: | AltScore: NA


EXTERNAL ADVISORY BOARD MEMBERS

Harvey J. Cohen, M.D.
Division Chief of Geriatrics, Director of the Center for the Study of Aging and Human Development, Duke University Medical Center
Serving since 2003 (18 years)

Luigi Ferrucci, M.D., Ph.D.
NIA Scientific Director, Senior Investigator and Chief, Longitudinal Studies Section
Serving since 2003 (18 years)

Joan E. Bailey-Wilson, Ph.D.
Head, Statistical Genetics Section; Co-Branch Chief, Inherited Disease Research Branch; National Human Genome Research Institute; National Institutes of Health
Serving since 2008 (13 years)

Gerald Beck, Ph.D.
Section Head, Clinical Trials; Design and Analysis, Department of Quantitative Health Sciences, Cleveland Clinic Foundation
Serving since 2013 (8 years)

Howard Bergman, M.D.
Chair, Department of Family Medicine, Professor of Family Medicine, Medicine and Oncology, Dr. Joseph Kaufmann Professor of Geriatric Medicine, McGill University
Serving since 2013 (8 years)


RECOGNITION AND AWARDS (2020-2021)

Recognition and Awards not specified.

MINORITY RESEARCH

General Brief Description of Minority Activities:

Janiece Taylor, PhD: Pilot Study. "Pilot Behavioral Intervention to Address Pain and Frailty in Older African-American Women."

Karen Bandeen-Roche, PhD: RC1 Development Project: includes analyses of frailty measurement variance by race in the National Health and Aging Trends Study.




Minority Trainee(s):
  • Janiece Taylor, PhD, Assistant Professor
    Janiece Taylor, PhD: Pilot Study. "Pilot Behavioral Intervention to Address Pain and Frailty in Older African-American Women."

Minority Grant(s):