BOSTON PEPPER CENTER
Claude D. Pepper Older Americans Independence Center


  Principal Investigator    Shalender Bhasin, M.D.    
  Program Administrator    Molly Lukas    mlukas@bwh.harvard.edu
 
I. CENTER DESCRIPTION
 

The Boston OAIC is unique in its thematic focus on Function Promoting Therapies (FPTs) and its positioning across the entire spectrum of translational science from mechanism elucidation, preclinical proof-of-concept studies, biomarker validation, epidemiologic investigation to randomized trials of FPTs. The Boston OAIC integrates 19 NIH-funded studies of function promoting therapies, 3 Research Education Component projects, 3 pilot projects, and 3 developmental projects into an interdisciplinary program that is supported by a Leadership and Administrative Core, a Research Education Component (REC), a Pilot and Exploratory Studies Core (PESC), and 3 resource cores (Function Assessment Core, Preclinical Discovery Core, Biostatistical and Data Analysis Core). Our REC and PESC candidates include several rising stars in Geriatrics and Gerontology, including 3 Beeson and K grant awardees. The REC will recruit the most promising stars from a vast reservoir of talent at Harvard, Tufts and BU, and train them through a didactic education and mentored research program. Integration will be achieved by the PROMOTE Program that includes a research concierge service, research meetings, annual retreats, a website and a newsletter. The Boston OAIC is well integrated with the the Harvard Geriatrics and Gerontology research community and programs, including its T32 training grant, Harvard Clinical Translational Science Institute, the Roybal Center, The New England Geriatrics Research Clinical Education Center, and the Glenn Foundation Center for Biology of Aging.

Boston OAIC’s unique strengths include its focus on Function Promoting Therapies, emphasis on translation and commercialization, access to a large pool of talented young investigators, its extension across the entire spectrum of translational research, and its infrastructure for developing intellectual property and companies, and supporting several seminal randomized trials of FPTs.


II. RESEARCH, RESOURCES AND ACTIVITIES
  A. CORES
  Biostatistical Design and Analysis Core (BDAC)
Leader 1:    Thomas Travison, PhD   TGT@hsl.harvard.edu
Leader 2:    Paola Sebastiani, PhD   
Leader 3:    Ralph D’Agostino, PhD   
Leader 4:    Karol Pencina, PhD   
The BDAC provides collaborative support in the design, execution and analysis of clinical trials and epidemiology studies conducted at the Boston OAIC. Additionally, the BDAC provides mentoring and collaborative opportunities for students and junior faculty in quantitative aspects of the study of physical function and impairments in aging. The BDAC is equipped to provide critical services on a consulting basis (e.g. in an advisory capacity in critical review of study data collection procedures) and more formally (e.g. in conducting simulation studies and power calculation). Furthermore, the BDAC provides support for ongoing projects by providing critical review and expertise in evaluating study conduct, or more extensive, pre-specified contributions to trial objectives. Support services for study completion are also available in providing guidance and assistance in statistical analyses, as well as co-authorship of abstracts and manuscripts describing study results.

Development Projects Core
Leader 1:    Alan M. Jette, PT, PhD, F.A.P.T.A.   ajette@bu.edu
The Developmental Projects core funds pilot projects chosen based on their innovation and translational value, and the need and potential of novel methods to advance OAIC projects

Functional Assessment Core (FAC)
Leader 1:    Roger Fielding, PhD   roger.fielding@tufts.edu
Leader 2:    Thomas Storer, Ph.D.   
The FAC represents a strategic interdisciplinary alliance between the Muscle Mechanics and Metabolomics Laboratory, the Laboratory of Exercise Physiology and Physical Performance and the Health and Disability Research Institute at Boston University and the Nutrition, Exercise Physiology and Sarcopenia Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. The core provides standardized, state-of-the-art technologies to measure muscle performance, functional limitations, and disability in human and animal studies for OAIC’s pilot and exploratory projects and for several OAIC related projects funded through other sources.

Leadership and Administrative Core (LAC)
Leader 1:    Shalender Bhasin, MD   sbhasin@partners.org
Leader 2:    Roger Fielding, PhD   
Leader 3:    Lewis A. Lipsitz, MD   lipsitz@hsl.harvard.edu
The LAC is responsible for stimulating, sustaining, evaluating, and reporting OAIC’s progress towards its goals and enabling integration of OAIC activities. In addition to providing administrative support, the LAC coordinates the activities of Boston OAIC’s investigators, resource cores, its conferences, and career development activities.

Pilot and Exploratory Studies Core (PESC)
Leader 1:    Monty Montano, PhD   MAMONTANO@research.bwh.harvard.edu
Leader 2:    Douglas P. Kiel, MD   
Within the context of the OAIC’s overall mission, the Pilot and Exploratory Studies Core (PESC) aims to provide catalytic support – seed funding, core support, and mentorship – for innovative pilot research projects that generate data on the mechanisms of FPT action to facilitate more definitive mechanistic studies, feasibility data to guide efficacy trials, hypothesis generating or proof-of-concept exploratory studies and retrospective analysis of existing epidemiologic data that inform FPT interventions.

Preclinical Discovery care
Leader 1:    Ravi Jasuja, PhD   
The ability to genetically modify rodents has increased the need to assess reproducibly and quantifiably, the phenotype of these animals with respect to body composition and physical function. In addition to utilizing the small animal resource services, the Preclinical Discovery Core (PDC) provides the infrastructural and consultative support for non-invasive measurements of alterations in body composition, muscle performance, physical function and metabolic performance to facilitate longitudinal studies of FPTs during aging and metabolic stress. The PDC is also continuing its mission to spearhead innovation- development of novel 7Tesla MRI techniques to provide mechanistic insights into FPT interventions.

Research Education Component (REC)
Leader 1:    Lewis A. Lipsitz, MD   lipsitz@hsl.harvard.edu
Leader 2:    Amy Wagers, PhD   
Leader 3:    Edward Marcantonio, MD   
The overall goal of the Research Education Component (REC) of the Boston OAIC is to train future independent research scientists who have the knowledge and the skill to translate fundamental mechanisms of disease and disability into novel interventions that can improve the health, physical function, and well-being of people as they age. The REC achieves this by selecting the most promising early career scientists from clinical and basic science disciplines and providing them with both collective and individual educational activities, research experiences, mentoring, and career guidance that will enable them to acquire future career development or research awards and ultimately become leaders in translational research devoted to the discovery of function promoting therapies (FPTs).

II. RESEARCH, RESOURCES AND ACTIVITIES (continued...)
  B. RESEARCH (16 Projects Listed)
 
1. Project Title: UNCOVERING MOLECULAR EFFECTORS OF MAMMALIAN AGING
  Leader(s): WAGERS, AMY JO
    HARVARD UNIVERSITY
    NIH DP1AG063419 / (2018-2023)
  Project Summary Aging is the single largest risk factor for most chronic degenerative diseases, including cardiovascular,musculoskeletal and neurodegenerative dysfunctions, and age-associated diseases now represent the mostrapidly growing unmet medical need in our society. Yet, while certain ?hallmarks of aging? have been defined,the critical molecular mediators that drive (and oppose) mammalian aging phenotypes have yet to besystematically explored, due in part to the technological challenges of applying classic functional geneticapproaches, which require the laborious generation and aging(!) of complex gene-specific germline andconditional knockout alleles, to studies of aging physiology. As this substantial knowledge gap presents asignificant impediment to developing new therapies for human aging pathologies, we aim in this project toestablish a new, more facile approach to interrogating the genes and pathways that regulate mammalian organfunction and repair throughout life. Our approach will take advantage of a unique in vivo genome editing system through which we canexperimentally induce programmable mutations into the genomes of stem cells in the blood and skeletalmuscle in intact animals, without the requirement for stem cell isolation and transplantation. By targetingendogenous stem cells, we allow for the maintenance and propagation of these mutations but circumvent theneed to remove these cells their native biological niche, which can induce cellular stress and alter stem cellbehavior by exposure to non-physiological ex vivo conditions. We also enable rapid testing of potentialcombinatorial gene effects, in multiple genetic backgrounds and in mice of various ages. Thus, our approachprovides a more powerful, and higher throughput, view into the molecular effectors of organismal aging, whichwill allow us to test previously unapproachable hypotheses regarding the impact of somatic mutagenic eventsin aging organ systems and to identify novel regulators that may drive the precocious onset of, or mediateprotection from, degenerative phenotypes across organ systems. Taken together, our work will yield new platform technologies for interrogating mammalian gene functionsin vivo, new insights into fundamental mechanisms of aging physiology and regenerative biology, and new andpotentially broadly useful methods for effecting genetic therapies in situ.
 
2. Project Title: ROLE OF MICRORNAS ON AGE AND CONTRACTION-INDUCED SKELETAL MUSCLE GROWTH
  Leader(s): RIVAS, DONATO A
    TUFTS UNIVERSITY BOSTON
    NIH K01AG047247 / (2015-2020)
  DESCRIPTION (provided by applicant): The age-associated loss of skeletal muscle mass and function (sarcopenia) is associated with substantial social and economic costs. The plasticity and adaptability of skeletal muscle to contraction (i.e. resistance-exercise) is a fundamental physiological event leading to larger and more robust skeletal muscle. However, muscle growth in response to resistance exercise (RE), like other anabolic stimuli, is attenuated in older adults The cause of aberrant muscle adaptation with aging is complex. Recent work has revealed a novel role for small non-coding RNAs, called microRNAs (miRNA) in the regulation of gene expression. Using an integrated bioinformatics analysis of protein-coding gene and miRNA array data from young and older men, I identified ten specific miRNAs as important regulators of muscle plasticity (Plasticity Related miRs [PR-miRs]) leading to the transcriptional response to exercise and lean mass in young and older men. However, the precise mechanisms underlying the expression of PR-miRs on age-related changes in muscle anabolism and sarcopenia are currently unknown. Thus, the overall objective of this K01 application will be to determine the mechanistic role(s) of these PR-miRs in skeletal muscle adaptation to anabolic stimulation in 1) healthy young, 2) sarcopenic older and 3) age- and functionally-matched non-sarcopenic older males and females. This will be accomplished by determine the differences in expression of PR-miRs with aging and sarcopenia in response to anabolic stimulation (AIM 1). Mechanistically determine the extent to which manipulation of PR-miR levels in vitro, in human primary myocytes, can reverse anabolic resistance observed with age and sarcopenia (AIM 2) and the effect of altering PR-miRs levels on skeletal muscle growth and development (AIM 3). This project will improve our understanding of the molecular mechanisms that contribute to the loss of skeletal muscle and eventually leading to the development of drug therapies for the treatment of sarcopenia in the ever growing aging population. The mentorship team includes, Dr. Roger Fielding, a leader in aging research and muscle biology, Dr. Kenneth Walsh, a cardiovascular researcher and leading molecular biologist, Dr. Laurence Parnell a computational biologist and authority in gene and miRNA expression analysis, Dr. Thomas Gustafsson a physician-scientist and clinical researcher and Dr. Thomas Travison an expert in biostatistics. The mentorship team has a variety of know-how in every facet of this project including, conducting human clinical trials and skeletal muscle biology, computational biology and genomics and molecular biology and mechanisms. The proposed career development plan includes research-oriented and didactic training at Tufts University, Boston University and the Karolinska Institute in Stockholm,Sweden. The pursuit of the specific aims of the research project, the multidisciplinary mentorship team and the career development plan will facilitate a transition to an independent research career.
 
3. Project Title: ROLE OF THE GUT MICROBIOME AND THE SERUM METABOLOME ON LEAN MASS AND PHYSICAL FUNCTION IN OLDER ADULTS
  Leader(s): LUSTGARTEN, MICHAEL S
    TUFTS UNIVERSITY BOSTON
    NIH K01AG050700 / (2016-2020)
  DESCRIPTION (provided by applicant): In older adults (70+ years), reduced lean body mass and physical function are associated with increased disability, hospitalization, morbidity and mortality. Because older adults are the fastest growing global subpopulation, identification of mechanisms that underlie the maintenance of lean mass and physical function will be important for addressing the public health priority of healthy aging. Gut bacteria may be involved in mechanisms that underlie the maintenance of lean mass and physical function. In support of this hypothesis, in multiple publications I recently reported significant associations between circulating gut bacteria-related metabolites with these outcomes in older adults. Accordingly, my over- arching hypothesis is that is gut bacteria are associated with and are causatively involved in mechanisms that underlie the maintenance of lean mass and physical function in older adults. To test this hypothesis, I propose to: characterize the association between fecal bacteria with lean mass and physical function (AIM 1), test the causative role of gut bacteria on the maintenance of lean mass and physical function by colonizing germ-free mice with fecal bacteria from older adults (AIM 2), and examine potential mechanisms that link gut bacteria with these outcomes by identifying associations between gut bacteria and serum metabolites with lean mass and physical function (AIM 3). Based on results obtained from the proposed study, I expect to progress towards an independent research career by designing and conducting clinical and translational studies aimed at targeted modulation the gut microflora, which may be a novel and innovative means for improving lean mass and physical function, and for addressing the public health priority of healthy aging in older adults. To accomplish these objectives I will need additional training. The proposed career development plan includes specialized training, coursework, and seminars that will allow me to: 1) learn and apply the bioinformatic methods that are used to analyze and interpret the gut microbiome and serum metabolome, and 2) design and conduct clinical and translational studies aimed at improving lean mass and physical function in older adults. In addition, I have organized a multi-disciplinarymentoring (Drs. Huttenhower, O'Toole and Fielding) and collaborative (Drs. Jones and Garrett) team that has extensive experience in every facet of this project including computational biology, the microbiome, the metabolome, gut bacterial transfer into germ-free mice, and in conducting clinical studies in older adults, which collectively will foster my development in theseareas. The knowledge, skills and experience that I will acquire through the proposed career development and research plans of this project are necessary to compete for R-series and other independent investigator grants, thereby allowing me to achieve my career goal of becoming an independent research scientist.
 
4. Project Title: AGING-ASSOCIATED DYSREGULATION OF THE HYPOXIA PATHWAY LIMITS SKELETAL MUSCLE REGENERATION
  Leader(s): SINHA, INDRANIL
    BRIGHAM AND WOMEN'S HOSPITAL
    NIH K76AG059996 / (2018-2023)
  Project Summary/Abstract This proposal describes a five-year training program and career development plan for Dr. IndranilSinha. Dr. Sinha is a prior trainee of a National Institute of Aging-sponsored Postdoctoral Individual NationalResearch Service Award (F32). He is a current awardee of a Research and Education Core Grant through theBoston Pepper Center and the National Institute of Aging. He has completed clinical training in Plastic andReconstructive Surgery and is board-certified through the American Board of Plastic Surgery. He is nowembarking on a research and career development program under the mentorship of Amy Wagers, Ph.D.,Professor of Medicine, Harvard Medical School. Dr. Wagers is an accomplished researcher in skeletal muscleregeneration and has a history of mentoring trainees who go on to successful, independent research careers.Additional mentoring will be provided by Dr. Shalender Bhasin, a world-renowned researcher on sarcopenia,and Dr. Laurie Goodyear, an expert on exercise physiology. Dr. Sinha's career development plan includesutilization of educational resources at Brigham and Women's Hospital, Joslin Diabetes Center, and HarvardMedical School. Career development support will also be provided by the Brigham and Women's HospitalDepartment of Surgery, where the principle investigator will serve as an attending physician during the periodof funding. Dr. Sinha has developed a clear timeline for publication of his work in peer-reviewed journals,presentations at national meetings, establishment of an Aging Interest Group within Plastic Surgery, and plansfor the development of independent research projects and continued research funding. Dr. Sinha is interested in developing novel treatment strategies for aging-associated loss of skeletalmuscle regeneration. He is investigating mechanisms by which aging alters hypoxia pathway signaling andskeletal muscle regenerative potential in a murine model. He found that two key factors in the hypoxiapathway, aryl hydrocarbon receptor nuclear translocator (ARNT) and vascular endothelial growth factor(VEGF), are severely dysregulated in skeletal muscle in aging and may lead to a loss of skeletal muscleregenerative potential. Furthermore, using a genetically modified mouse model, he demonstrated that musclespecific loss of ARNT recapitulates diminished skeletal muscle regeneration as associated with aging. Buildingon these intriguing preliminary data, the central goals of this project are to (1) mechanistically define the role ofhypoxia pathway signaling and its impact on muscle regeneration in aging, (2) identify interventions to restoreARNT and VEGF signaling to preserve skeletal muscle myogenic potential, and (3) determine whether musclehypertrophy in response to exercise, which is known to require skeletal muscle regeneration and hypoxiasignaling, is limited in aging secondary to loss of ARNT.
 
5. Project Title: HEALTH OUTCOMES OF TAI CHI IN SUBSIDIZED SENIOR HOUSING
  Leader(s): LIPSITZ, LEWIS; WAYNE, PETER MICHAEL ;
    HEBREW REHABILITATION CENTER FOR AGED
    NIH R01AG025037 / (2006-2021)
  DESCRIPTION (provided by applicant): Elderly people living in low-income housing facilities represent one of our nation's largest, most functionally impaired, economically disadvantaged, and understudied populations that account for a disproportionate share of Medicare spending. This revised competitive renewal application aims to improve the health and reduce the health care costs of this population by conducting a cluster randomized controlled trial of Tai Chi exercises vs. health education and social calls in 16 housing facilities in cities surrounding Boston. The proposal builds upon previously successful studies by Drs. Lipsitz, Wayne, and others showing multiple benefits of Tai Chi exercises in elderly people with a variety of diseases and disabilities. A randomized, controlled pilot study supported by the current R37 grant that thisapplication seeks to renew, showed that 12 weeks of Tai Chi exercises tailored to the abilities of frail seniors living in supportive housing facilities can improve balance, gait, and physical function. The proposed study aims are to determine the effects of Tai Chi exercises conducted at least twice weekly over a 1 year period on 1) functional performance measured by the Short Physical Performance Battery and 2) health care utilization and costs determined from Medicare claims data in poor, multiethnic, elderly residents of low income housing facilities. Secondary outcomes will include person-centered measures such as physical function, cognition, psychological well-being, falls, self-efficacy, and satisfaction. We hypothesize that compared to the control intervention, Tai Chi will significantly improve physical function and reduce health care utilization and costs. This study will prepare the necessary training and protocol manuals for widespread dissemination of Tai Chi programs in housing facilities across the nation. It will also provide estimates of potential Medicare cost savings that can be used to justify future health insurance payments for this intervention. The previous experience of the Co-Principal Investigators and their colleagues at Harvard Medical School and Brandeis University in aging research, clinical trials, functional assessment, Medicare claims analyses, and Tai Chi interventions will help assure the project's success.
 
6. Project Title: REGULATION AND FUNCTION OF GROWTH DIFFERENTIATION FACTOR 11 DURING DEVELOPMENT AND AGING
  Leader(s): WAGERS, AMY JO
    HARVARD UNIVERSITY
    NIH R01AG048917 / (2016-2021)
  DESCRIPTION (provided by applicant): Healthy skeletal muscle is essential to sustain normal physical function, and muscle undergoes multiple developmental and functional transitions during fetal, neonatal and adult life. In the latest stages of life, impaired muscle homeostasis and reduced muscle regenerative potential lead to progressive loss of muscle mass and strength. Importantly, reduced muscle function in elderly individuals is one of the strongest predictors of imminent mortality, suggesting that improved understanding of the fundamental mechanisms underlying muscle aging and the development of novel strategies to intervene in this process, would have tremendous impact on lifespan and quality of life of the growing population of aged individuals experiencing degenerative muscle decline. This project is aimed at increasing our understanding of skeletal muscle function throughout life by focusing on a novel circulating hormone called Growth Differentiation Factor 11 (GDF11, also known as Bone Morphogenic Protein 11, or BMP11). Extensive published and preliminary data indicate that GDF11 plays a key role in modulating the homeostatic remodeling of skeletal muscle fibers and the regenerative activity of muscle stem cells (satellite cells) at particular stages of life. GDF1 protein circulates at high levels in neonatal and young adult animals (including humans), but declines dramatically with advancing age and in concert with the emergence of multiple age-associated pathologies in muscle and other tissues. Data from our recently published manuscripts indicate that raising the levels of circulating GDF11 in aged mice can reverse certain age-related pathologies, including recovery of satellite cell numbers in resting muscle and restoration of muscle regenerative potential after mild muscle injury. However, overproduction of this protein in younger mice subjected to severe muscle damage may have a detrimental effect. In this project, we will answer questions crucial to understanding the regulation and activity of this new candidate rejuvenating factor for aged muscle, and its potential for regulating developmental and aging phenotypes in mice and humans by: (1) defining the cellular source(s) of GDF11 throughout life and clarifying the basis for the age-dependent decline of this hormone and its potential age- and injury-dependent effects on muscle repair, (2) evaluating the impact on development and homeostasis of removal of GDF11 at discrete stages of life or in discrete GDF11- producer cells, and (3) assessing age-regulated changes in GDF11 abundance and function in human sera and correlating these with muscle performance, body composition and overall physical function in individuals with or without mobility limitations. Together, these studies will provide critical insights into muscle developmental biology and aging and may validate a promising new candidate therapeutic for the reversal of age-related skeletal muscle dysfunction.
 
7. Project Title: EPIDEMIOLOGY AND RISK OF ANTIPSYCHOTIC USE IN HOSPITALIZED ELDERLY WITH DELIRIUM
  Leader(s): KIM, DAE HYUN
    BRIGHAM AND WOMEN'S HOSPITAL
    NIH R01AG056368 / (2018-2021)
  PROJECT SUMMARY/ABSTRACTEach year 2 million older adults receive antipsychotic medications (APMs) in the hospital, mainly for delirium.Although the harms of APMs are well documented and their use has declined in older adults with dementia, thescope and risk of off-label APM exposure in hospitalized older adults remain largely unknown. The objective ofthis application is to determine the prescribing trends and risks of APMs and their alternatives in hospitalizedolder adults with postoperative delirium. The research team will analyze data from 2 national inpatient data-bases and detailed clinical data from 5 NIH-funded cohorts to generate evidence on the comparative safety ofAPMs and their alternatives that is generalizable to real-world patients. The central hypothesis is that off-labelAPM use is associated with increased risk of adverse events compared with no use in hospitalized older adultswith postoperative delirium; in particular, newer ?atypical? APMs may be more harmful than conventional ?typi-cal? APM for short-term use. The applicant's preliminary data showed that, although atypical APMs may be asharmful as typical APM in hospitalized older surgical patients, use of atypical APMs and certain psychoactivedrugs has been rising in recent years. The APM prescribing rates also vary more than 30 folds across the UShospitals, which suggests potentially inappropriate prescribing. Lack of safety data on APMs for hospitalizedolder adults, as well as little evidence on safer alternatives seems to contribute to these trends. The rationalefor this application is that the available safety data from dementia patients may not generalize to hospitalizedolder surgical patients and that evidence on the comparative safety of APMs and other psychoactive drugs inroutine care patients cannot be generated from clinical trials alone. This 3-year proposal has 3 specific aims:1) determine the risk of in-hospital mortality, institutional discharge, prolonged length of stay, and readmissionassociated with different APMs in older patients with delirium after major surgery; 2) determine the risk of in-hospital non-fatal adverse events associated with different APMs; and 3) identify psychoactive drugs that maybe prescribed as therapeutic alternatives to APMs by examining longitudinal prescribing trends. The investiga-tors will apply innovative research methodologies of leveraging existing large claims datasets and cohort datato enhance generalizability to routine care populations, increase statistical power to address safety for patientsubgroups and individual drugs, and reduce bias. By conducting validation of case-identification algorithms,the investigators will improve how in-hospital adverse events are measured in inpatient drug safety research.The impact of this research is significant, because high-quality evidence on the comparative safety of APMsand their alternatives can guide clinicians to reduce excessive APM use and promote rational and safe APMprescribing, thereby improving safety and clinical care of older surgical patients.
 
8. Project Title: INVESTIGATING GDF11 AND MSTN AS CANDIDATE CIRCULATING GERONIC FACTORS
  Leader(s): WAGERS, AMY JO
    HARVARD UNIVERSITY
    NIH R01AG057428 / (2017-2021)
  Project SummaryStudies using heterochronic parabiosis, a surgical intervention that establishes bi-directional cross-circulationbetween young and old animals, strongly indicate the existence of blood-borne factors that regulate theregeneration and homeostasis of skeletal muscle, and other tissues, in an age-dependent manner. Work frommy lab and others implicate the circulating proteins Growth Differentiation Factor 11 (GDF11) and Myostatin(MSTN) as candidate geronic factors responsible for the transposition of aging phenotypes in muscle inheterochronically joined mice.GDF11 and MSTN are closely related ligands of the TGF? superfamily that share 89% sequence identity intheir receptor-binding domains and exhibit highly overlapping patterns of receptor binding. Yet despite thesesimilarities, published reports suggest that these two proteins may exert opposing influences on aging muscle.In particular, we showed that systemic supplementation of GDF11 levels in aged mice (by injection ofrecombinant GDF11 protein) can elicit a striking reversal of age-related deficits in muscle repair capacity,remodel myofiber ultrastructure, and enhance muscle strength and endurance. GDF11 expression also hasbeen positively correlated with lifespan in studies of multiple species. Conversely, analyses of MSTN-deficientanimals suggest that MSTN acts normally to limit muscle growth and slow regeneration after injury, and thatmild suppression of MSTN in mice may have a positive impact on lifespan. Importantly, these effects of GDF11and MSTN appear to be both dose- and context-specific, which has raised some confusion and controversyregarding their respective influences on aging and health span.In this proposal, we aim to overcome prior experimental challenges to generate a clear molecular geneticunderstanding of the respective roles of GDF11 and MSTN in muscle aging, their mechanistic relationship toone another, and their relevance as therapeutically actionable geronic proteins. Our studies will use highlyspecific LC-MS/MS assays and mouse genetic models to track circulating protein levels and manipulateGDF11 and MSTN expression in young, middle-aged and aged mice, and in the young or aged partners ofheterochronic parabiosis, both in steady state and in response to muscle injury. The importance of this work isunderscored by human studies linking differences in serum levels of GDF11 and MSTN with clinical outcomesin several aging-related diseases. As such, our proposed work has a high potential impact for the identificationand future development of promising targets to combat age-related muscle dysfunction and is directlyresponsive to RFA-AG-17-002: Characterization of Circulating Pro- and Anti-Geronic Proteins and Peptides.
 
9. Project Title: PROSPECTIVE MONITORING OF NEWLY APPROVED CARDIOVASCULAR DRUGS IN OLDER ADULTS WITH FRAILTY
  Leader(s): KIM, DAE HYUN
    BRIGHAM AND WOMEN'S HOSPITAL
    NIH R01AG062713 / (2019-2023)
  PROJECT SUMMARY/ABSTRACTCardiovascular disease (CVD) affects 70% of older adults and remains the leading cause of morbidity and mor-tality in the United States. Several new drugs have recently been approved for CVD, but not enough is knownabout their utilization, benefits and risks in frail older patients. Since conducting a clinical trial in frail older adultscan be costly and impractical, there is a pressing need for innovative strategies to generate evidence on newCVD drugs in a timely manner. The objective of this application is to establish a near-real-time prospectivemonitoring program in Medicare data to evaluate the benefit of new CVD drugs for older adults with frailty. Aprospective monitoring program seeks to find early effectiveness and safety signals of new drugs by updatingthe analysis at regular intervals as new Medicare data become available. The investigators will incorporate anovel claims-based frailty index into the monitoring program to generate timely evidence on disease-specific andpatient-centered net benefit of new drugs by frailty status. The central hypothesis is that disease-specific benefitand net benefit are determined by a patient's degree of frailty. Disease-specific benefit will be evaluated usingclinical trial endpoints of effectiveness (e.g., CVD events) and safety (e.g., bleeding), and net benefit in terms ofthe number of days alive and spent at home, or ?home time?. To conduct this work, the investigators will analyzeMedicare data on 6 new CVD drugs approved in 2011-2017: 3 anticoagulants vs warfarin for atrial fibrillation, 2antiplatelets vs clopidogrel for atherosclerotic CVD, and an angiotensin receptor-neprilysin inhibitor vs enalaprilfor systolic heart failure. The validity and reproducibility of the results will be enhanced through the linkage of asubset of Medicare data to electronic health records and a national survey to supplement clinical information,and external validation of the Medicare data analysis in 2 large commercial databases. In the next 4 years, theinvestigators will accomplish 3 specific aims: 1) evaluate the temporal trends and predictors of new CVD druguse in frail and non-frail older adults with CVD over 2011-2020; 2) determine disease-specific benefit (deaths,CVD and safety events) and net benefit (home time) of 6 new CVD drugs compared with alternative therapies;3) identify patient characteristics that can predict net benefit (home time) with new CVD drugs compared withalternative therapies. This proposal's innovative approach, which combines near-real-time prospective monitor-ing, a claims-based frailty score, and the patient-centered outcome of home time, offers a readily scalable andfeasible framework for comparative effectiveness and safety studies of newly approved medications. The impactof the proposed research is significant because timely evidence generated from real-world healthcare data canenable clinicians to optimize prescribing of new CVD drugs based on a patient's frailty and expected net benefit.
 
10. Project Title: RISK FACTORS FOR AGE RELATED BONE LOSS
  Leader(s): KIEL, DOUGLAS P.
    HEBREW REHABILITATION CENTER FOR AGED
    NIH R01AR041398 / (1991-2020)
  DESCRIPTION (provided by applicant): The Framingham Osteoporosis Study (R01 AR41398 'Risk Factors for Age Related Bone Loss'), an ancillary study of the Framingham Heart Study, has contributed significantly over the past 25 years to the understanding of genetic and lifestyle factors contributing to osteoporosis, sarcopenia, and fractures. Based on the growing epidemic of obesity, and conflicting data regarding the role of visceral adiposity on musculoskeletal health, in this continuation of the Framingham Osteoporosis Study, we will determine the role of visceral adipose tissue (VAT) on bone density, microarchitecture, and strength, as well as on muscle density, and fracture. We are proposing three aims. In Aim 1, to determine the association between VAT and bone density, microarchitecture, and strength, we will measure VAT using longitudinal whole body DXA scans (a baseline previously obtained, and a follow up to be acquired as part of this project) and perform High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) measurements of the distal radius and tibia, and during a clinic visit of the Framingham Study 3rd Generation Cohort (Gen3). In Aim 2 we will determine the association of VAT and muscle density using longitudinal QCT scans already obtained in the Gen3 Cohort. For both Aim 1 and Aim 2, we will also determine if the effects of VAT on bone density, microarchitecture and strength (Aim 1), and on muscle density (Aim 2), are partly attributable to physical activity levels, inflammation, adipokines, or sex steroid metabolism. In Aim 3, we will perform a Mendelian randomization analysis to obtain an unbiased estimate of the VAT-fracture association by using a genetic risk score ('instrumental variable') to predict incident fracture. The proposed study will be the largest investigation of the potentially deleterious effects of visceral adiposity on the musculoskeletal system. Each of our hypotheses is based on preliminary data from our past grant cycle or from other research grants involving the Framingham Study. The project is significant for several reasons. First, obesity has become one of the most important health problems in the U.S. Second, the precise role of visceral adiposity on the musculoskeletal system has not been previously investigated, and the proposed work will fill this gap, especially with longitudinal data on VAT and to be obtained longitudinal measures of muscle density using existing CT scans. Third, we will investigate potential underlying mechanisms for the effects of VAT on the musculoskeletal system. Finally we will obtain an unbiased estimate of the VAT-fracture association using Mendelian randomization analysis. Overall, the results of this study will provide the best available data on the effects of visceral adiposity on the musculoskeletal system.
 
11. Project Title: A SELECTIVE ANDROGEN RECEPTOR MODULATOR FOR SYMPTOM MANAGEMENT IN PROSTATE CANCER
  Leader(s): BHASIN, SHALENDER
    BRIGHAM AND WOMEN'S HOSPITAL
    NIH R01NR014502 / (2015-2020)
  DESCRIPTION (provided by applicant): Improved survival of men with prostate cancer has focused attention on the impact of treatment on quality of life, especially on sexual symptoms, physical dysfunction, and fatigue, which are important contributors to poor quality of life. Androgen deficiency is common and an important remediable contributor to these symptoms; however, uncertainty about the risk of testosterone replacement in men with a history of prostate cancer has rendered physicians reticent to use testosterone even in men who are deemed cured after a radical prostatectomy. A novel selective androgen receptor modulator - LY SARM - is ideal for alleviating symptoms of androgen deficiency and mitigating concerns about disease recurrence associated with testosterone therapy because it acts as an androgen agonist on the muscle, bone, and sexual function, but as an antagonist on the prostate. Our objective is to conduct a staged, double-blind, placebo-controlled, dose response study to determine the efficacy and safety of LY SARM in improving sexual symptoms, fatigue, and physical dysfunction in men with prostate cancer who have undergone radical prostatectomy for organ-localized prostate cancer, are deemed to be at low risk of recurrence, and who have androgen deficiency. In stage 1, 10 subjects will be randomized to either placebo or 1 mg dose. If no safety signal is observed, additional subjects will be randomized to 0, 1 or 5 mg dose. Our first aim is to compare 0, 1 or 5 mg of LY SARM in men, who have undergone radical prostatectomy for organ-localized prostate cancer, have symptomatic androgen deficiency, and with regard to sexual function (sexual activity score, sexual desire, erectile function, distress ad sexual life quality). The second aim is to compare the effects of 0, 1 or 5 mg of SARM on fatigue, well-being and affectivity balance, and disease-specific quality of life. Our third aim isto determine whether SARM administration improves muscle mass and strength, physical function, and aerobic capacity more than placebo. Men =19-years, who have undergone radical prostatectomy for organ-localized cancer (pT2,N0,M0), Gleason score =6, undetectable PSA (<0.1 ng/mL) for >2 years after radical prostatectomy and symptoms of sexual dysfunction, fatigue, or physical dysfunction, and low total (<300 ng/dL) and/or free testosterone <60 pg/ml, will be randomized to 0, 1 or 5 mg LY SARM daily for 3 months. Outcomes include changes in sexual symptoms (sexual activity score, sexual desire, erectile function, sexual distress, sexual life quality), affectivity balance, mood, fatigue, disease-specific quality of life, measures of physical function, muscle strength, and aerobic capacity (VO2max , VO2 peak, lactate threshold). We will monitor hematocrit, PSA, and biochemical recurrence, defined as 'PSA of =0.2 ng/mL with a confirmatory level of =0.2 ng/mL'. Careful selection of subjects with very low risk of recurrence, rigorous safety monitoring, clear stopping rules, an independent DSMB, selection of symptomatic men with low testosterone, and good trial design (block randomization, placebo-controlled, blinded) will maximize the chances of successful outcome of this SARM trial in a very needy patient population.
 
12. Project Title: FRAILTY, STATINS, AND CARDIOVASCULAR DISEASE BURDEN IN OLDER ADULTS
  Leader(s): ORKABY, ARIELA R
    HARVARD UNIVERSITY
    NIH R03AG060169 / (2018-2020)
  Cardiovascular disease (CVD) remains the leading cause of death in older adults. Statins are highly effectivecholesterol-lowering medications used for primary prevention of CVD, and are the most commonly prescribedmedications. After age 75, data on the effects of statins are limited to guide statin prescribing recommendations.However, even where the evidence is clear, statins remain under-prescribed. Reasons for under-prescribing ofproven CVD prevention medications such as statins in older adults are many, and may include competingmedical conditions, adverse side effects (e.g., myalgias), and frailty. Frailty is a multidimensional state ofdecreased physiologic reserve associated with an increased risk of CVD and poor clinical outcomes. The agingpopulation is heterogeneous and a one-size fits all approach may not be appropriate. In particular, understandingthe utility of statins for prevention of CVD in individuals who are vulnerable or frail is critical. Therefore, theresearch activities in this GEMSSTAR award will use a retrospective design to (1) understand patterns of statinuse in a large cohort of older US veterans aged 65 and older, over 15 years of follow up, with particular attentionto the relationship between frailty, myalgias and statin use; and (2) examine the association between statin usefor primary prevention of CVD in pre-frail and frail older veterans and cardiovascular events, health careutilization, and mortality. This work will inform the design of future clinical trials of statins for prevention of CVDin older adults accounting for heterogeneity of aging and frailty. In addition to the pharmacoepidemiologic studyproposed, this GEMSSTAR award includes mentorship, coursework, and seminars in advanced epidemiologicand statistical methods, geriatrics, and cardiology. The research and career development activities will preparethe applicant for her long-term goal of a research career in geriatric preventive cardiology and will informpreventive care for the aging population.
 
13. Project Title: ASBMR THREE YEAR SYMPOSIA
  Leader(s): CAULEY, JANE ANN; CAWTHON, PEGGY MANNEN ; EDWARDS, CLAIRE ; KIEL, DOUGLAS P. ;
    AMERICAN SOCIETY FOR BONE & MINERAL RES
    NIH R13AR074882 / (2019-2022)
  The American Society for Bone and Mineral Research (ASBMR), the largest professional, scientific andmedical society established to bring together clinical and laboratory-based scientists who are involved in thestudy of bone, mineral and musculoskeletal science, has had a successful history of conducting annual topicalmeetings funded by single year NIH R13 grants since 2002. In 2015, ASBMR received a three-year R13 tocover three pre-meeting symposia for 2016-2018.This application seeks funding for a three-year R13 grant toadvance the field of musculoskeletal diseases by focusing on three specific areas of scientific research in2019, 2010 and 2021: 1) ?Muscle: The Path Forward to New Therapeutic Targets?; 2) ?The Seed and Soil:Therapeutic Targets for Cancer in Bone?; 3) ?Biology of the Aging Skeleton: Implications for FracturePrevention?. These three areas cover a range of topics that collectively contribute to major clinical morbiditydisability and mortality. The overall objective of this R13 is to stimulate further advances that will result inimproved patient care for musculoskeletal diseases by bringing together the best researchers for each of thethree symposia that will be held in conjunction with the ASBMR Annual Meetings. Each of the three symposiawill review the state of the art in each topic area, exchanging ideas with attendees, and stimulating theinteraction between young and established researchers. For each of the three symposia, attendees will beencouraged to attend the subsequent ASBMR Annual Meetings for additional opportunities to interact withmusculoskeletal researchers. Agendas for all three years have been developed by an organizing committeewith committed speakers and chairs for the first two years. The agendas include established and younginvestigators, women and men. Since about half of ASBMR membership is from outside the US, we alsoinclude a number of key international speakers. At the end of each meeting, a ?dine-around? evening isplanned to allow direct interaction between young investigators and more senior speakers at the meeting. In2019, the symposium will appraise the emerging basic science of muscle (autophagy muscle, mitochondria,stem and satellite cells), translational research including development of potential therapeutic targets and toclinical research. In 2020, the symposium will focus on recent advances in the contributions of the bonemicroenvironment to the pathophysiology, prevention and treatment of cancer in bone. The 2021 symposiumwill bring together experts in geroscience and skeletal biology to enhance our understanding of biological agingthat is being targeted by therapeutic interventions to increase health span and apply them to the agingskeleton.
 
14. Project Title: 2019 STEM CELLS AND CANCER GORDON RESEARCH CONFERENCE(GRC)AND GORDON RESEARCH SEMINAR(GRS)
  Leader(s): WAGERS, AMY JO
    GORDON RESEARCH CONFERENCES
    NIH R13CA236216 / (2019-2020)
  Project Summary/Abstract This proposal requests partial support for the seventh Gordon Research Conference on Stem Cells andCancer, which will take place on March 24-29, 2019 in Ventura, California (USA). The specific aim of thisconference is to provide a forum for presentation, discussion and interaction among a diverse, interdisciplinarygroup of researchers with interests in organogenesis, tumorigenesis, stem cell function and therapy. Speakersand participants will engage in deep discussions of recent advances and new ideas related to thedevelopmental, metabolic and (epi)genomic mechanisms driving organogenesis and tumorigenesis.The meeting is chaired by Dr. Amy J. Wagers (Harvard University), with Dr. C?dric Blanpain (Universit? Librede Bruxelles) serving as vice chair. The planned agenda includes presentations from key leaders in the fieldsof cancer biology, stem cell biology and regenerative medicine, and thus will attract a highly interdisciplinarygroup of researchers who do not frequently interact (since most regenerative biology meetings lackrepresentation from cancer biologists, and vice versa). The meeting will therefore act as a catalyst for newcollaborations and cross-fertilization of ideas (a long-term goal of the Gordon Research Conferences). Theexciting scientific program we have planned for the meeting further highlights the diversity of contributors tothis research area (53% of invited speakers are female and/or members of under-represented minority groups)and explores cutting-edge topics of particular interest to the National Institutes of Health (NIH), including: therole of metabolism in regulating tumor growth and metastasis; developmental signals and mechanisms thatmodulate stem cell function and are usurped for tumor formation; genetic and epigenetic modifiers of genomestability and cancer emergence; and emerging therapies to promote tumor cell clearance, eradicate tumor-propagating stem cells and enhance organ repair. The 2019 Gordon Research Conference on Stem Cells and Cancer will also include a Gordon ResearchSeminar (GRS), a 2-day ?pre-meeting? of early career scientists in a highly stimulating and inclusiveenvironment that promotes the open exchange of information and establishment and growth of peer networks.The GRS will be held from March 23-24, 2019 at the same venue in Ventura, CA, and is chaired by Dr. JillGoldstein (Harvard University). The GRS provides additional opportunities for junior trainees to present theirwork and receive crucial feedback and mentorship both from their peers and from more establishedinvestigators, making this meeting a particularly excellent training opportunity for junior investigators. The specific set of integrated and complementary research topics that will be addressed in the 2019 StemCells and Cancer GRS/GRC is distinct from other conferences, and the unique structure of the GRS and GRCprovide for maximal, productive interactions among scientists in industry and academia with differentexperimental approaches and at different career stages.
 
15. Project Title: RESTRICTED MEAN SURVIVAL TIME TO INTERPRET CLINICAL TRIALS FOR TREATMENT DECISION-MAKING IN OLDER ADULTS
  Leader(s): KIM, DAE HYUN
    HEBREW REHABILITATION CENTER FOR AGED
    NIH R21AG060227 / (2019-2021)
  PROJECT SUMMARY/ABSTRACTPatient-centered care of older adults with multimorbidity involves shared decision-making based on accuratecommunication of evidence. In clinical trials, treatment effect is conventionally summarized in terms of relativerisk reduction using hazard ratios and absolute risk reduction. Despite widespread use, these conventionalmeasures based on probabilities are not well understood by clinical community and often misleading in treatmentdecision-making. We have recently proposed restricted mean survival time (RMST) as a patient-centric outcomemetric that can be intuitively interpreted as the average event-free survival time up to a pre-specified time point.Treatment effect can be summarized using RMST difference, which means ?gain or loss in event-free survivaltime due to treatment in a pre-specified period?. Since it is expressed on a time scale that most clinicians andpatients can relate to, it has great potential to facilitate shared decision-making in older adults, which involvesassessment of benefit within a defined time frame, such as the remaining life expectancy. The objective of thisapplication is to determine the usefulness of RMST in treatment decision-making, using an example of intensivevs. standard blood pressure lowering strategies in older adults. Our hypothesis is that presenting evidence usingRMST difference, rather than absolute and relative risk reduction, would be more effective in reducing patients'uncertainty about treatment choice. To test our hypothesis, we will accomplish 2 specific aims to: 1) determinethe benefit of intensive vs. standard blood pressure lowering strategies using RMST difference in older adultsand identify characteristics associated with a greater RMST benefit; and 2) evaluate the effect of evidence com-munication formats based on RMST difference vs. conventional measures on patients' uncertainty in treatmentdecision-making. For Aim 1, we will analyze 2 publicly available datasets from the Action to Control Cardiovas-cular Risk in Diabetes Trial and Systolic Blood Pressure Intervention Trial to estimate RMST difference. For Aim2, we will conduct an online survey of 200 community-dwelling older adults and an in-person survey of 100residents at a local senior housing site. Participants will be randomized to one of the 2 evidence presentationformats, RMST vs. conventional measures, to assess the effect on reducing uncertainty in decision-making. Wewill conduct focus group interviews of 20-30 survey participants to further understand the reasoning and contextbehind their choice. Our approach is innovative, because we apply an intuitive and methodologically robustRMST to analyze and interpret clinical trial data, and rigorously evaluate the acceptability and understandingfrom the patient's perspective by adopting quantitative and qualitative design. The impact of this research isexpected to be significant, because our method has great potential to be generalized to other clinical trials withtime-to-event endpoints to facilitate shared decision-making in older adults.
 
16. Project Title: RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY-SUPPLEMENT
  Leader(s): BHASIN, SHALENDER; GILL, THOMAS MICHAEL ; REUBEN, DAVID B. ;
    BRIGHAM AND WOMEN'S HOSPITAL
    NIH U01AG048270 / (2014-2020)
  SummaryThe STRIDE Trial is the largest pragmatic, cluster randomized, parallel group superiority trial with practicesstratified by healthcare system and patients nested within practices. Fall injuries are a major public healthproblem. Thirty percent of people over the age of 65 fall each year, and for those over 75 the rates are evenhigher. Serious fall injuries, including fractures and other falls leading to medical attention, are a commonsource of disability and death among the elderly. This randomized trial will determine the effectiveness of anevidence-based, multifactorial, patient-centered intervention to reduce the risk of serious fall injuries amongnon-institutionalized older persons. The original target sample size was 6,000 participants enrolled from 86practices to provide 90% power to detect a 20% reduction in the rate of the primary outcome with interventionrelative to control. Later, the duration of the trial was extended to a total of 40 months (20 months ofrecruitment and an additional 20 months of follow-up), which reduced the target sample size to 5,322participants. Recruitment ended after 20 months on March 31, 2017, with a total of 5,451 participants enrolled.The intervention phase ended on November 30, 2018 and follow-up will end on March 31, 2019.The primary aim of this administrative supplemental application is to request funds to carry out trial close-outactivities of the STRIDE Trial necessitated by the extension of the intervention and the follow-up period as aresult of the two DSMB-approved modifications in the trial's design. In December 2017, the trial's DSMB andthe NIA approved the extension of the duration of the study from 36 months (18 months of recruitment and aminimum 18 months of follow-up) to 40 months (20 months of recruitment and a minimum of 20 months offollow-up). Based on an analysis of the event rate of the primary outcome in a closed session, the trial's DSMBand the NIA staff directed the study team to Extend the study from a minimum of 20 and maximum of 40months follow-up to a minimum of 24 and maximum of 44 months of follow-up. Final end date of the study,including the analytic phase is now extended to April 30, 2020. Because of the extension of the interventionduration and the follow-up period, the project's end date was extended to April 30, 2020. The close-out fundsare necessary for completing the data collection, adjudication of the primary outcome, analyses of the primaryand secondary outcomes as described in the peer-reviewed and funded grant application, preparation of thestudy reports and manuscripts, and orderly close-out of the trial. The supplement does not change the specificaims or scope of the parent grant application and is required for trial's close-out activities resulting fromimplementation of the DSMB and NIA-approved extension of the intervention and follow-up period.
 
II. RESEARCH, RESOURCES AND ACTIVITIES (continued...)
  C. PILOT/EXPLORATORY PROJECTS (0 Pilot Projects Listed)
 
  No pilot/exploratory projects.
II. RESEARCH, RESOURCES AND ACTIVITIES (continued...)
  D. DEVELOPMENT PROJECTS (0 Development Projects Listed)
 
  No development projects.
III. CAREER DEVELOPMENT
 
REC Scholar, Research & Grants Funded During Pepper Supported Time Years Publications
 

None specified.

IV. PUBLICATIONS
  2020
 
  1. Association of Fish Oil and Physical Activity on Mobility Disability in Older Adults.
    Balachandran A, Gundermann DM, Walkup MP, King AC, Ambrosius WT, Kritchevsky SB, Pahor M, Newman AB, Manini TM
    Med Sci Sports Exerc, 2020 Apr, 52(4): 859-867
    https://doi.org/10.1249/MSS.0000000000002195 | PMID: 31688650 | PMCID: PMC7123515
    Citations: | AltScore: 4.85
  2. The Impact of Frailty on Long-Term Patient-Oriented Outcomes after Emergency General Surgery: A Retrospective Cohort Study.
    Lee KC, Streid J, Sturgeon D, Lipsitz S, Weissman JS, Rosenthal RA, Kim DH, Mitchell SL, Cooper Z
    J Am Geriatr Soc, 2020 Feb 11, 68(5): 1037-1043
    https://doi.org/10.1111/jgs.16334 | PMID: 32043562 | PMCID: PMC7234900
    Citations: | AltScore: 33.7
  3. Impact and Lessons From the Lifestyle Interventions and Independence for Elders (LIFE) Clinical Trials of Physical Activity to Prevent Mobility Disability.
    Pahor M, Guralnik JM, Anton SD, Ambrosius WT, Blair SN, Church TS, Espeland MA, Fielding RA, Gill TM, Glynn NW, Groessl EJ, King AC, Kritchevsky SB, Manini TM, McDermott MM, Miller ME, Newman AB, Williamson JD
    J Am Geriatr Soc, 2020 Apr, 68(4): 872-881
    https://doi.org/10.1111/jgs.16365 | PMID: 32105353 | PMCID: PMC7187344
    Citations: | AltScore: 10.4
  4. Sarcopenia is associated with severe erectile dysfunction in older adults: a population-based cohort study.
    Park H, Jang IY, Han M, Lee H, Jung HW, Lee E, Kim DH
    Korean J Intern Med, 2020 Apr 21
    https://doi.org/10.3904/kjim.2019.148 | PMID: 32306710
    Citations: | AltScore: 7.75
  5. Patterns of multi-domain cognitive aging in participants of the Long Life Family Study.
    Sebastiani P, Andersen SL, Sweigart B, Du M, Cosentino S, Thyagarajan B, Christensen K, Schupf N, Perls TT
    Geroscience, 2020 Jun 8
    https://doi.org/10.1007/s11357-020-00202-3 | PMID: 32514870
    Citations: | AltScore: 0.5
  6. The functional implications and modifiability of resting-state brain network complexity in older adults.
    Zhou J, Lo OY, Halko MA, Harrison R, Lipsitz LA, Manor B
    Neurosci Lett, 2020 Feb 16, 720: 134775
    https://doi.org/10.1016/j.neulet.2020.134775 | PMID: 31972253 | PMCID: PMC7069223
    Citations: | AltScore: 1.35
   
  2019
 
  1. A Global Loss of Dio2 Leads to Unexpected Changes in Function and Fiber Types of Slow Skeletal Muscle in Male Mice.
    Carmody C, Ogawa-Wong AN, Martin C, Luongo C, Zuidwijk M, Sager B, Petersen T, Roginski Guetter A, Janssen R, Wu EY, Bogaards S, Neumann NM, Hau K, Marsili A, Boelen A, Silva JE, Dentice M, Salvatore D, Wagers AJ, Larsen PR, Simonides WS, Zavacki AM
    Endocrinology, 2019 May 1, 160(5): 1205-1222
    https://doi.org/10.1210/en.2019-00088 | PMID: 30951174 | PMCID: PMC6482039
    Citations: 1 | AltScore: 4.45
  2. Corrigendum: Nutritional Supplementation With Physical Activity Improves Muscle Composition in Mobility-Limited Older Adults, The VIVE2 Study: A Randomized, Double-Blind, Placebo-Controlled Trial.
    Englund DA, Kirn DR, Koochek A, Zhu H, Travison TG, Reid KF, von Berens ?, Melin M, Cederholm T, Gustafsson T, Fielding RA
    J Gerontol A Biol Sci Med Sci, 2019 Nov 13, 74(12): 1993
    https://doi.org/10.1093/gerona/glz138 | PMID: 31242295 | PMCID: PMC6853669
    Citations: | AltScore: NA
  3. Physical Activity and Performance Impact Long-term Quality of Life in Older Adults at Risk for Major Mobility Disability.
    Groessl EJ, Kaplan RM, Rejeski WJ, Katula JA, Glynn NW, King AC, Anton SD, Walkup M, Lu CJ, Reid K, Spring B, Pahor M
    Am J Prev Med, 2019 Jan, 56(1): 141-146
    https://doi.org/10.1016/j.amepre.2018.09.006 | PMID: 30573142 | PMCID: PMC6309909
    Citations: 2 | AltScore: 1.75
  4. Middle-Aged Men With HIV Have Diminished Accelerometry-Based Activity Profiles Despite Similar Lab-Measured Gait Speed: Pilot Study.
    Hale TM, Guardigni V, Roitmann E, Vegreville M, Brawley B, Woodbury E, Storer TW, Sax PE, Montano M
    JMIR Mhealth Uhealth, 2019 Feb 1, 7(2): e11190
    https://doi.org/10.2196/11190 | PMID: 30707104 | PMCID: PMC6376331
    Citations: 3 | AltScore: NA
  5. Statins for Primary Prevention in Those Aged 70 Years and Older: A Critical Review of Recent Cholesterol Guidelines.
    Hawley CE, Roefaro J, Forman DE, Orkaby AR
    Drugs Aging, 2019 Aug, 36(8): 687-699
    https://doi.org/10.1007/s40266-019-00673-w | PMID: 31049807 | PMCID: PMC7245614
    Citations: 1 | AltScore: 6.75
  6. A Practical Two-Stage Frailty Assessment for Older Adults Undergoing Aortic Valve Replacement.
    Hosler QP, Maltagliati AJ, Shi SM, Afilalo J, Popma JJ, Khabbaz KR, Laham RJ, Guibone K, Kim DH
    J Am Geriatr Soc, 2019 Oct, 67(10): 2031-2037
    https://doi.org/10.1111/jgs.16036 | PMID: 31211413 | PMCID: PMC6800747
    Citations: 2 | AltScore: 27.19
  7. Characteristics of sarcopenia by European consensuses and a phenotype score.
    Jang IY, Lee E, Lee H, Park H, Kim S, Kim KI, Jung HW, Kim DH
    J Cachexia Sarcopenia Muscle, 2020 Apr, 11(2): 497-504
    https://doi.org/10.1002/jcsm.12507 | PMID: 31863645 | PMCID: PMC7113507
    Citations: 1 | AltScore: 3
  8. Evaluation of Changes in Functional Status in the Year After Aortic Valve Replacement.
    Kim DH, Afilalo J, Shi SM, Popma JJ, Khabbaz KR, Laham RJ, Grodstein F, Guibone K, Lux E, Lipsitz LA
    JAMA Intern Med, 2019 Mar 1, 179(3): 383-391
    https://doi.org/10.1001/jamainternmed.2018.6738 | PMID: 30715097 | PMCID: PMC6439710
    Citations: 5 | AltScore: 138.6
  9. Low Dietary Protein Intakes and Associated Dietary Patterns and Functional Limitations in an Aging Population: A NHANES analysis.
    Krok-Schoen JL, Archdeacon Price A, Luo M, Kelly OJ, Taylor CA
    J Nutr Health Aging, 2019, 23(4): 338-347
    https://doi.org/10.1007/s12603-019-1174-1 | PMID: 30932132 | PMCID: PMC6507527
    Citations: 2 | AltScore: 225.28
  10. What Aging with HIV Means in the Year 2019.
    Levin J, Montano M
    AIDS Res Hum Retroviruses, 2019 Nov/Dec, 35(11-12): 982-984
    https://doi.org/10.1089/AID.2019.0114 | PMID: 31373209 | PMCID: PMC6863065
    Citations: | AltScore: 1
  11. The Role of the Gut Microbiome on Skeletal Muscle Mass and Physical Function: 2019 Update.
    Lustgarten MS
    Front Physiol, 2019, 10: 1435
    https://doi.org/10.3389/fphys.2019.01435 | PMID: 31911785 | PMCID: PMC6933299
    Citations: 1 | AltScore: 32.3
  12. Self-Reported Head Trauma Predicts Poor Dual Task Gait in Retired National Football League Players.
    Manor B, Zhou J, Lo OY, Zhu H, Gouskova NA, Yu W, Zafonte R, Lipsitz LA, Travison TG, Pascual-Leone A
    Ann Neurol, 2020 Jan, 87(1): 75-83
    https://doi.org/10.1002/ana.25638 | PMID: 31693765 | PMCID: PMC6973030
    Citations: 1 | AltScore: 11.25
  13. Vitamin D supplements and prevention of cardiovascular disease.
    Orkaby AR, Djousse L, Manson JE
    Curr Opin Cardiol, 2019 Nov, 34(6): 700-705
    https://doi.org/10.1097/HCO.0000000000000675 | PMID: 31425172 | PMCID: PMC7112175
    Citations: 1 | AltScore: 1
  14. Impact of frailty on outcomes in surgical patients: A systematic review and meta-analysis.
    Panayi AC, Orkaby AR, Sakthivel D, Endo Y, Varon D, Roh D, Orgill DP, Neppl RL, Javedan H, Bhasin S, Sinha I
    Am J Surg, 2019 Aug, 218(2): 393-400
    https://doi.org/10.1016/j.amjsurg.2018.11.020 | PMID: 30509455 | PMCID: PMC6536365
    Citations: 2 | AltScore: 13
  15. Screening Value of Social Frailty and Its Association with Physical Frailty and Disability in Community-Dwelling Older Koreans: Aging Study of PyeongChang Rural Area.
    Park H, Jang IY, Lee HY, Jung HW, Lee E, Kim DH
    Int J Environ Res Public Health, 2019 Aug 7, 16(16):
    pii: E2809. https://doi.org/10.3390/ijerph16162809 | PMID: 31394719 | PMCID: PMC6720732
    Citations: | AltScore: NA
  16. The Association Between Social Engagement, Mild Cognitive Impairment, and Falls Among Older Primary Care Patients.
    Quach LT, Ward RE, Pedersen MM, Leveille SG, Grande L, Gagnon DR, Bean JF
    Arch Phys Med Rehabil, 2019 Aug, 100(8): 1499-1505
    https://doi.org/10.1016/j.apmr.2019.01.020 | PMID: 30825422 | PMCID: PMC7282702
    Citations: | AltScore: NA
  17. Translating the Lifestyle Interventions and Independence for Elders Clinical Trial to Older Adults in a Real-World Community-Based Setting.
    Reid KF, Laussen J, Bhatia K, Englund DA, Kirn DR, Price LL, Manini TM, Liu CK, Kowaleski C, Fielding RA
    J Gerontol A Biol Sci Med Sci, 2019 May 16, 74(6): 924-928
    https://doi.org/10.1093/gerona/gly152 | PMID: 30010808 | PMCID: PMC6521918
    Citations: 1 | AltScore: 28.5
  18. Sphingosine-1-phosphate analog FTY720 reverses obesity but not age-induced anabolic resistance to muscle contraction.
    Rivas DA, Rice NP, Ezzyat Y, McDonald DJ, Cooper BE, Fielding RA
    Am J Physiol Cell Physiol, 2019 Sep 1, 317(3): C502-C512
    https://doi.org/10.1152/ajpcell.00455.2018 | PMID: 31241988 | PMCID: PMC6766615
    Citations: | AltScore: 2.25
  19. Delirium Incidence and Functional Outcomes After Transcatheter and Surgical Aortic Valve Replacement.
    Shi SM, Sung M, Afilalo J, Lipsitz LA, Kim CA, Popma JJ, Khabbaz KR, Laham RJ, Guibone K, Lee J, Marcantonio ER, Kim DH
    J Am Geriatr Soc, 2019 Jul, 67(7): 1393-1401
    https://doi.org/10.1111/jgs.15867 | PMID: 30882905 | PMCID: PMC6612597
    Citations: 1 | AltScore: 12.45
  20. \Like a Man of 70 Years\: Aging and the Words We Use.
    Streiter S, Orkaby AR
    J Am Geriatr Soc, 2019 Oct, 67(10): 2208-2209
    https://doi.org/10.1111/jgs.15989 | PMID: 31112284 | PMCID: PMC6800756
    Citations: | AltScore: 18.35
  21. Association between Diet Quality and Frailty Prevalence in the Physicians' Health Study.
    Ward RE, Orkaby AR, Chen J, Hshieh TT, Driver JA, Gaziano JM, Djousse L
    J Am Geriatr Soc, 2020 Apr, 68(4): 770-776
    https://doi.org/10.1111/jgs.16286 | PMID: 31840808 | PMCID: PMC7156335
    Citations: 1 | AltScore: 16.45
  22. Neural correlates of perceived physical and mental fatigability in older adults: A pilot study.
    Wasson E, Rosso AL, Santanasto AJ, Rosano C, Butters MA, Rejeski WJ, Boudreau RM, Aizenstein H, Gmelin T, Glynn NW, LIFE Study Group.
    Exp Gerontol, 2019 Jan, 115: 139-147
    https://doi.org/10.1016/j.exger.2018.12.003 | PMID: 30528639 | PMCID: PMC6331252
    Citations: | AltScore: 1.5
  23. Association of Frailty With Recovery From Disability Among Community-Dwelling Older Adults: Results From Two Large U.S. Cohorts.
    Wu C, Kim DH, Xue QL, Lee DSH, Varadhan R, Odden MC
    J Gerontol A Biol Sci Med Sci, 2019 Mar 14, 74(4): 575-581
    https://doi.org/10.1093/gerona/gly080 | PMID: 29648574 | PMCID: PMC6601525
    Citations: 3 | AltScore: 5.2
  24. Defining Frailty in Research Abstracts: A Systematic Review and Recommendations for Standardization.
    Yaksic E, Lecky V, Sharnprapai S, Tungkhar T, Cho K, Driver JA, Orkaby AR
    J Frailty Aging, 2019, 8(2): 67-71
    https://doi.org/10.14283/jfa.2019.4 | PMID: 30997918 | PMCID: PMC7238433
    Citations: | AltScore: 10.45


V. EXTERNAL ADVISORY BOARD MEMBERS
 
No EAB Members specified.

VI. RECOGNITION AND AWARDS (2019-2020)
 
Recognition and Awards not specified.

VII. MINORITY RESEARCH
 
General Brief Description of Minority Activities:
Not defined.

 
No minority trainee information specified.
 
No minority grant information specified.