BOSTON PEPPER CENTER
Claude D. Pepper Older Americans Independence Center

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


CORES
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.

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).

Pilot and Exploratory Studies Core (PESC)
Leader 1:    Monty Montano, PhD   MMONTANO@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.

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.

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.

CAREER DEVELOPMENT
REC Scholar, Research & Grants Funded During Pepper Supported Time Years Publications
 
Indranil Sinha, M.D.
Assistant Professor / Harvard Medical School
Assistant Professor of Surgery
  • Beeson Award K76: Aging-associated dysfunction of hypoxia pathway limits skeletal muscle regeneration

2019-  6 (1 1st/Sr)
Michael Lustgarten, PhD
Scientist / Tufts University
Scientist
  • K01: Role of the gut microbiome and the serum metabolome on lean mass and physical function in older adults.

2019-  5 (2 1st/Sr)
Ariela Orkaby, MD, MPH
Assistant Professor / Harvard Medical School
Assistant Professor
  • GEMSSTAR R03: Frailty, statins and cardiovascular disease burden in older adults.

2019-  14 (5 1st/Sr)
Kieran F. Reid, PhD, MPH
Assistant Professor / Tufts University
Scientist
2019-  4 (1 1st/Sr)
Lien Quach, MD, PhD
Scientist / Boston VA Research Institute
Scientist
2019-  6 (2 1st/Sr)

Past Scholars

PILOT/EXPLORATORY PROJECTS (5 Pilot Projects Listed)
1. Project Title: PESC: Loss of a lncRNA exacerbates aging associated functional decline of skeletal muscle.
  Leader: Ronald Neppl, PhD
 

The project is based on a novel gene identified in a screen of lncRNAs whose expression is dysregulated in an established mouse model of skeletal muscle hypertrophy. Gm14635, now referred to as Kratos appears necessary for the maintenance of muscle mass and myogenic expression of transcription factors, and decreases with advancing age, thus suggesting that dysregulation of Kratos may be involved in aging related sarcopenia.

 
2. Project Title: REC: Physical function: the roles of social engagement and cognitive impairment
  Leader: Lien Quach, MD, PhD, MPH
 

The project is to examine the protective effect of rich social engagement on MCI at the baseline and physical function after 4 years of follow-up using the archive data from Boston Rehabilitative Impairment Study of the Elderly Boston (Boston RISE).

 
3. Project Title: PESC: Mediterranean diet, related antioxidants and frailty.
  Leader: Shivani Sahni, PhD
 

The study proposes that higher intake of antioxidants from a Mediterranean style diet will be associated with reduced risk of frailty and slower progression of frailty over 16 years and this association will be partly mediated by specific markers of oxidative stress. We will address this work via two aims using up to 1,746 participants from a well-characterized cohort, the Framingham Offspring Study.

 
4. Project Title: PESC: Mechanistic basis of differential regulation of polyamine pathway by testosterone in the prostate and androgen-responsive skeletal muscle.
  Leader: Rajan Singh, PhD
 

The study proposes that ornithine decarboxylase (ODC1) plays an essential role in the biosynthesis of polyamines in the prostate and in mediating the selective trophic effects of testosterone in this tissue.

 
5. Project Title: REC: Translating exercise into the community to preserve independence among older adults with motoric cognitive risk syndrome.
  Leader: Kieran Reid, PhD
 

The study will examine and characterize the effects of translating LIFE physical activity intervention into a community setting while specifically targeting older adults with motoric cognitive risk syndrome and at increased risk for developing dementia.

 
DEVELOPMENT PROJECTS (1 Development Projects Listed)
1. Project Title: Strategy to rapidly develop patient-reported outcome assessments for therapeutic interventions in older individuals.
  Leader: Marcia Testa, MPH, PhD
  Core(s):
 

This project goals are to develop, apply and evaluate clinical utility of “measures, tools, and endpoints that assess a minimum list of impacts that matter most to patients (e.g., patient-reported outcomes, PROs) and are likely to demonstrate change relating to disease burden, treatment burden and physical function. Specific applications to conditions and diseases of older individuals that impact the quality of life, functioning and feelings of older individuals within the context therapeutic interventions and programs. 

 
RESEARCH (28 Projects Listed)
1. Project Title: UNCOVERING MOLECULAR EFFECTORS OF MAMMALIAN AGING
  Leader(s): WAGERS, AMY JO
    HARVARD UNIVERSITY
    NIH DP1AG063419 / (2018-2023)
  Core(s):
  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 a...
 
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)
  Core(s):
  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 e...
 
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)
  Core(s):
  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 ...
 
4. Project Title: DEVELOPMENT AND VALIDATION OF A FRAILTY INDEX USING CLAIMS DATA FOR PHARMACOEPIDEMIOLOGIC STUDIES IN OLDER ADULTS
  Leader(s): KIM, DAE HYUN
    BRIGHAM AND WOMEN'S HOSPITAL
    NIH K08AG051187 / (2015-2018)
  Core(s):
  DESCRIPTION (provided by applicant): This application is submitted by Dae Hyun Kim, MD, MPH, ScD in response to RFA-AG-15-016, the K08 Paul B. Beeson Clinical Scientist Development Award in Aging. Dr. Kim is a board-certified geriatrician and epidemiologist at Brigham and Women's Hospital and Instructor in Medicine at Harvard Medical School. Dr. Kim has a solid background in clinical ge...
 
5. 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)
  Core(s):
  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 ha...
 
6. 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)
  Core(s):
  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 populat...
 
7. Project Title: REVERSING AGE-RELATED DYSFUNCTION OF SKELETAL MUSCLE STEM CELLS
  Leader(s): WAGERS, AMY JO
    HARVARD UNIVERSITY
    NIH R01AG033053 / (2009-2016)
  Core(s):
  Project Summary/Abstract: Aging of multicellular organisms typically involves progressive decline in the body's ability to maintainhomeostatic cell replacement and to regenerate tissues and organs after injury. Skeletal muscle, in particular,regenerates robustly through most of adult life but fails to do so in old age. Age-acquired defects in musclefunction profoundly impact the health of older in...
 
8. Project Title: MECHANISMS OF TESTOSTERONE ACTION
  Leader(s): BHASIN, SHALENDER
    BRIGHAM AND WOMEN'S HOSPITAL
    NIH R01AG037193 / (2004-2016)
  Core(s):
  DESCRIPTION (provided by applicant): Testosterone administration increases skeletal muscle mass and strength, and decreases fat mass in men, but the mechanisms by which testosterone regulates body composition are poorly understood. In the previous funding cycle, we demonstrated that testosterone and DHT promote the differentiation of adult, multipotent. mesenchymal stem cells into myogenic linea...
 
9. Project Title: OPTIMIZING PROTEIN INTAKE IN OLDER AMERICANS WITH MOBILITY LIMITATIONS
  Leader(s): BHASIN, SHALENDER; APOVIAN, CAROLINE M ;
    BRIGHAM AND WOMEN'S HOSPITAL
    NIH R01AG037547 / (2010-2016)
  Core(s):
  DESCRIPTION (provided by applicant): The recommended dietary allowance (RDA) for protein, set at 0.8 grams/kg/day for adult men and women, has engendered debate and many experts advocate protein intakes substantially above the RDA to help maintain muscle anabolism in older individuals. It is not known whether increasing protein intake in older Americans, whose current intake is below the RDA, i...
 
10. Project Title: CEREBROVASCULAR MECHANISMS OF SLOW GAIT AND FALLS
  Leader(s): LIPSITZ, LEWIS
    HEBREW REHABILITATION CENTER FOR AGED
    NIH R01AG041785 / (2013-2019)
  Core(s):
  DESCRIPTION (provided by applicant): This proposal leverages and extends the MOBILIZE Boston Study (MBS), which previously demonstrated significant relationships between abnormal cerebral blood flow (CBF) regulation, slow gait speed, and the development of falls in a representative population of elderly people living in the Boston metropolitan area. Our findings have led to the hypothesis that alt...
 
11. 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)
  Core(s):
  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, r...
 
12. 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)
  Core(s):
  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 prescribin...
 
13. Project Title: INVESTIGATING GDF11 AND MSTN AS CANDIDATE CIRCULATING GERONIC FACTORS
  Leader(s): WAGERS, AMY JO
    HARVARD UNIVERSITY
    NIH R01AG057428 / (2017-2021)
  Core(s):
  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 Diff...
 
14. 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)
  Core(s):
  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 ...
 
15. Project Title: BIOMARKERS FOR MUSCLE FUNCTION AND AGING IN CHRONIC HIV INFECTION
  Leader(s): MONTANO, MONTY A
    BRIGHAM AND WOMEN'S HOSPITAL
    NIH R01AI108541 / (2014-2019)
  Core(s):
  DESCRIPTION: In the United States, HIV infection has become a chronic disease with increasing evidence for an accelerated aging phenotype. By 2015, over half of HIV-infected individuals will be 50 years old or older. Notably, chronic HIV infection is associated with persistent inflammation, fibrosis and increased risk for frailty - conditions associated with muscl aging. We propose that persistent...
 
16. Project Title: RISK FACTORS FOR AGE RELATED BONE LOSS
  Leader(s): KIEL, DOUGLAS P.
    HEBREW REHABILITATION CENTER FOR AGED
    NIH R01AR041398 / (1991-2020)
  Core(s):
  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 co...
 
17. Project Title: TAI CHI AND FIBROMYALGIA
  Leader(s): WANG, CHENCHEN
    TUFTS MEDICAL CENTER
    NIH R01AT006367 / (2011-2018)
  Core(s):
  DESCRIPTION (provided by applicant): Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome that causes substantial physical and psychological impairment and costs over $25 billion annually. Current pharmacological therapies may be expensive, cause serious adverse effects, and fail to effectively improve pain and function. Thus, finding new and effective non-pharmacological treatments for...
 
18. 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)
  Core(s):
  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...
 
19. Project Title: FRAILTY, STATINS, AND CARDIOVASCULAR DISEASE BURDEN IN OLDER ADULTS
  Leader(s): ORKABY, ARIELA R
    HARVARD UNIVERSITY
    NIH R03AG060169 / (2018-2020)
  Core(s):
  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-prescrib...
 
20. 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)
  Core(s):
  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...
 
21. 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)
  Core(s):
  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, tumor...
 
22. 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)
  Core(s):
  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 under...
 
23. Project Title: PHASE II: RESEARCH AND COMMERCIALIZATION OF TRUT ALGORITHM FOR FREE TESTOSTERONE
  Leader(s): JASUJA, RAVI
    FUNCTION PROMOTING THERAPIES LLC
    NIH R44AG045011 / (2014-2019)
  Core(s):
  The measurement of testosterone (T) levels is central to the diagnosis of androgen disorders, such as hypogonadism in men and polycystic ovary syndrome (PCOS) in women. Circulating T is bound with high affinity to sex hormone binding globulin (SHBG) and with substantially lower affinity to albumin; only the free fraction is biologically active. Conditions that affect SHBG concentrations, such as a...
 
24. 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)
  Core(s):
  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 fall...
 
25. Project Title: THE ENRGISE STUDY
  Leader(s): PAHOR, MARCO; AMBROSIUS, WALTER T ;
    UNIVERSITY OF FLORIDA
    NIH U01AG050499 / (2015-2019)
  Core(s):
  DESCRIPTION (provided by applicant): Growing evidence from our group and others shows that low-grade chronic inflammation, characterized by elevations in plasma C-reactive protein, tumor necrosis factor alpha, and particularly Interleukin-6 (IL-6), is an independent risk factor o disability, impaired mobility, and lower walking speed. Low-grade chronic inflammation is a modifiable risk ...
 
26. Project Title: MUSCLE MASS AND STRENGTH CUTPOINTS IN PERSONS AT RISK OF MOBILITY DISABILITY-A1
  Leader(s): BHASIN, SHALENDER; CAWTHON, PEGGY MANNEN ;
    BRIGHAM AND WOMEN'S HOSPITAL
    NIH U01AG051421 / (2015-2018)
  Core(s):
  DESCRIPTION (provided by applicant): The age-related loss of muscle mass and strength is an important contributor to mobility disability, poor health outcomes, and death. It is important t identify older adults in whom mobility limitation is due to low muscle mass and strength because they may be potentially amenable to treatment with novel therapies that increase muscle mass and muscle...
 
27. Project Title: PROS (PATIENT REPORTED OUTCOMES) FOR CHILDREN AND YOUNG ADULTS WITH DISABILITIES
  Leader(s): JETTE, ALAN MAURICE; TULSKY, DAVID SCOTT ;
    BOSTON UNIVERSITY MEDICAL CAMPUS
    NIH U01AR057929 / (2009-2015)
  Core(s):
  DESCRIPTION (provided by applicant): The notion that children's quality of life instruments need to be designed and applied in a manner specific to children's developmental and cognitive needs is now widely accepted. It is somewhat unclear at what age a children's designed instrument will suffice, and at what age adult PROs can be used with confidence. Specific research needs to focus directly on ...
 
28. Project Title: VITAMIN D AND OMEGA-3 TRIAL (VITAL)
  Leader(s): MANSON, JOANN ELISABETH; BURING, JULIE E. ;
    BRIGHAM AND WOMEN'S HOSPITAL
    NIH U01CA138962 / (2009-2014)
  Core(s):
  DESCRIPTION (provided by applicant): We propose to conduct a large, cost-effective, randomized, double-blind, placebo-controlled, 2x2 factorial trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements in the primary prevention of cancer and cardiovascular disease (CVD). Data from laboratory...
 
PUBLICATIONS
2021
 
2020
  1. Markers of Iron Flux during Testosterone-Mediated Erythropoiesis in Older Men with Unexplained or Iron-Deficiency Anemia.
    Artz AS, Stephens-Shields AJ, Bhasin S, Ellenberg SS, Cohen HJ, Snyder PJ
    J Clin Endocrinol Metab, 2020 Nov 1, 105(11):
    pii: dgaa521. https://doi.org/10.1210/clinem/dgaa521 | PMID: 32785689 | PMCID: PMC7500468
    Citations: | AltScore: NA
  2. Adult-Onset Myopathy with Constitutive Activation of Akt following the Loss of hnRNP-U.
    Bagchi D, Mason BD, Baldino K, Li B, Lee EJ, Zhang Y, Chu LK, El Raheb S, Sinha I, Neppl RL
    iScience, 2020 Jul 24, 23(7): 101319
    https://doi.org/10.1016/j.isci.2020.101319 | PMID: 32659719 | PMCID: PMC7358745
    Citations: | AltScore: 1.25
  3. 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
  4. A Randomized Trial of a Multifactorial Strategy to Prevent Serious Fall Injuries.
    Bhasin S, Gill TM, Reuben DB, Latham NK, Ganz DA, Greene EJ, Dziura J, Basaria S, Gurwitz JH, Dykes PC, McMahon S, Storer TW, Gazarian P, Miller ME, Travison TG, Esserman D, Carnie MB, Goehring L, Fagan M, Greenspan SL, Alexander N, Wiggins J, Ko F, Siu AL, Volpi E, Wu AW, Rich J, Waring SC, Wallace RB, Casteel C, Resnick NM, Magaziner J, Charpentier P, Lu C, Araujo K, Rajeevan H, Meng C, Allore H, Brawley BF, Eder R, McGloin JM, Skokos EA, Duncan PW, Baker D, Boult C, Correa-de-Araujo R, Peduzzi P, STRIDE Trial Investigators.
    N Engl J Med, 2020 Jul 9, 383(2): 129-140
    https://doi.org/10.1056/NEJMoa2002183 | PMID: 32640131 | PMCID: PMC7421468
    Citations: 1 | AltScore: 272.596
  5. Associations of Endogenous Sex Hormones with Carotid Plaque Burden and Characteristics in Midlife Women.
    Cort?s YI, Barinas-Mitchell E, Suder Egnot N, Bhasin S, Jasuja R, Santoro N, Thurston RC
    J Clin Endocrinol Metab, 2020 Apr 1, 105(4):
    pii: dgz327. https://doi.org/10.1210/clinem/dgz327 | PMID: 31900485 | PMCID: PMC7077951
    Citations: 1 | AltScore: 257.1
  6. Loss of ARNT in skeletal muscle limits muscle regeneration in aging.
    Endo Y, Baldino K, Li B, Zhang Y, Sakthivel D, MacArthur M, Panayi AC, Kip P, Spencer DJ, Jasuja R, Bagchi D, Bhasin S, Nuutila K, Neppl RL, Wagers AJ, Sinha I
    FASEB J, 2020 Oct 8, 34(12): 16086-16104
    https://doi.org/10.1096/fj.202000761RR | PMID: 33064329
    Citations: | AltScore: 7.65
  7. Differential effects of testosterone on circulating neutrophils, monocytes, and platelets in men: Findings from two trials.
    Gagliano-Juc? T, Pencina KM, Guo W, Li Z, Huang G, Basaria S, Bhasin S
    Andrology, 2020 Jun 2, 8(5): 1324-1331
    https://doi.org/10.1111/andr.12834 | PMID: 32485095 | PMCID: PMC7484244
    Citations: | AltScore: 2.5
  8. Impact of Baseline Fatigue on a Physical Activity Intervention to Prevent Mobility Disability.
    Glynn NW, Gmelin T, Santanasto AJ, Lovato LC, Lange-Maia BS, Nicklas BJ, Fielding RA, Manini TM, Myers VH, de Rekeneire N, Spring BJ, Pahor M, King AC, Rejeski WJ, Newman AB, Lifestyle Interventions and Independence for Elders Study Group.
    J Am Geriatr Soc, 2020 Mar, 68(3): 619-624
    https://doi.org/10.1111/jgs.16274 | PMID: 31867713
    Citations: | AltScore: 22.45
  9. Estimation of ascertainment bias and its effect on power in clinical trials with time-to-event outcomes.
    Greene EJ, Peduzzi P, Dziura J, Meng C, Miller ME, Travison TG, Esserman D
    Stat Med, 2020 Dec 14
    https://doi.org/10.1002/sim.8842 | PMID: 33316841
    Citations: | AltScore: NA
  10. Self-reported sleep quality is associated with gut microbiome composition in young, healthy individuals: a pilot study.
    Grosicki GJ, Riemann BL, Flatt AA, Valentino T, Lustgarten MS
    Sleep Med, 2020 Sep, 73: 76-81
    https://doi.org/10.1016/j.sleep.2020.04.013 | PMID: 32795890 | PMCID: PMC7487045
    Citations: | AltScore: 16.75
  11. Dietary Sodium Intake and Sodium Density in the United States: Estimates From NHANES 2005-2006 and 2015-2016.
    Hu JR, Sahni S, Mukamal KJ, Millar CL, Wu Y, Appel LJ, Juraschek SP
    Am J Hypertens, 2020 Sep 10, 33(9): 825-830
    https://doi.org/10.1093/ajh/hpaa104 | PMID: 32619231 | PMCID: PMC7481988
    Citations: | AltScore: 4.55
  12. Cognition, Frailty, and Functional Outcomes of Transcatheter Aortic Valve Replacement.
    Kapadia M, Shi SM, Afilalo J, Popma JJ, Laham RJ, Guibone K, Kim DH
    Am J Med, 2020 Oct, 133(10): 1219-1222
    https://doi.org/10.1016/j.amjmed.2020.01.041 | PMID: 32199811 | PMCID: PMC7501150
    Citations: | AltScore: 6.55
  13. 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: 1 | AltScore: 33.7
  14. 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: 2 | AltScore: 13
  15. Multicomponent Intervention and Long-Term Disability in Older Adults: A Nonrandomized Prospective Study.
    Park CM, Oh G, Lee H, Jung HW, Lee E, Jang IY, Kim DH
    J Am Geriatr Soc, 2020 Nov 5
    https://doi.org/10.1111/jgs.16926 | PMID: 33155305
    Citations: | AltScore: NA
  16. 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, 35(5): 1245-1253
    https://doi.org/10.3904/kjim.2019.148 | PMID: 32306710 | PMCID: PMC7487308
    Citations: | AltScore: 7.75
  17. Perceived social isolation, social disconnectedness and falls: the mediating role of depression.
    Quach LT, Burr JA
    Aging Ment Health, 2020 Mar 5 1-6
    https://doi.org/10.1080/13607863.2020.1732294 | PMID: 32131617 | PMCID: PMC7483756
    Citations: | AltScore: 11
  18. 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, 42(5): 1335-1350
    https://doi.org/10.1007/s11357-020-00202-3 | PMID: 32514870 | PMCID: PMC7525612
    Citations: | AltScore: 1.75
  19. Risk Factors, Presentation, and Course of Coronavirus Disease 2019 in a Large, Academic Long-Term Care Facility.
    Shi SM, Bakaev I, Chen H, Travison TG, Berry SD
    J Am Med Dir Assoc, 2020 Oct, 21(10): 1378-1383.e1
    https://doi.org/10.1016/j.jamda.2020.08.027 | PMID: 32981664 | PMCID: PMC7447263
    Citations: 1 | AltScore: 52.3
  20. 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


EXTERNAL ADVISORY BOARD MEMBERS

Laura Niedernhofer, MD, PhD
University of Minnesota Medical School
Serving since 2016 (5 years)

Marco Pahor, MD
University of Florida Institute on Aging
Serving since 2016 (5 years)

Steven Kritchevsky, PhD
Wake Forest
Serving since 2016 (5 years)

Thomas Gill, MD
Yale University
Serving since 2016 (5 years)


RECOGNITION AND AWARDS (2020-2021)

Recognition and Awards not specified.

MINORITY RESEARCH

General Brief Description of Minority Activities:
Not defined.


Minority Trainee(s):
  • Donato Rivas, PhD, Scientist
    Training/Education: PhD in Biomedical Science (Bioenergetics) Research Interests: The role of substrates on cellular signaling pathways controlling skeletal muscle metabolism and growth; and how nutrition, aging and exercise contribute to alterations in skeletal muscle energy homeostasis. Research Project (Completed PESC): Circulating microRNA as novel predictors of skeletal muscle anabolic response in aged humans. Awards: K01

Minority Grant(s):
1. 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.