BOSTON PEPPER CENTER
Claude D. Pepper Older Americans Independence Center

Shalender Bhasin, M.D.
Principal Investigator (Brigham and Women’s Hospital Harvard Medical School)
  .   sbhasin@bwh.harvard.edu
Roger Fielding, PhD
Co-PI (Tufts University School of Medicine)
  .   rfield01@granite.tufts.edu
Lewis A. Lipsitz, MD
Co-PI (Beth Israel Deaconess Medical Center Hebrew SeniorLife Harvard Medical School)
  .   lipsitz@hsl.harvard.edu
Liz Torres
Program Administrator
  .   ltorres8@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@bwh.harvard.edu
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:    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:    Shalender Bhasin, MD   sbhasin@bwh.harvard.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:    Kieran Reid, Ph.D.   Kieran.Reid@tufts.edu
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
 
Hao Zhou, MD, PhD
Instructor in Surgery / Harvard Medical School
PESC: Donor and recipient age mismatches in organ transplantation transfer senescent cells impacting physical exercise capacity.
Donor and recipient age mismatches in organ transplantation transfer senescent cells impacting physical exercise capacity.
2020-2022 /
5 (total)
1 (1st/Sr)
 
Daniel Roh, MD
Assistant Professor / Boston University
REC-3: Contribution of Cellular Senescence to Delayed Wound Healing of Aging
Dr. Roh is an Assistant Professor of Surgery at Boston University School of Medicine in the field of Plastic and Reconstructive Surgery whose research focus is to discover new translational therapies that can reduce the burden of wounds for the older adult6. His project will test the hypothesis that senescent cell accumulation in aged skin contributes to impaired wound healing, and that reduction of these cells can be a valuable tool to improve wound healing in aged individuals. Using aged mice, he will determine the contribution of senescent cell accumulation to the impaired wound healing of aging. He will evaluate topical senolytic therapy as a potential treatment and determine the effect of reducing senescent cell burden on the impaired wound healing of aging. Rejuvenating and strengthening aged skin with senolytics could be used as a preventative measure to avoid wound complications in patients at risk for acute wounds that develop into chronic wounds. In addition, this project proposes to establish potential biomarkers of senescence and wound healing status. Dr. Roh’s mentors include LaDora Thompson PT PhD, Vladimir Botchkarev MD PhD, and Laura Niedernhofer, MD PhD. His project will utilize the Biostatistical Design and Analysis and the Preclinical Discovery Cores
2021-2022 /
20 (total)
10 (1st/Sr)
 
Sari Reisner, DSc.
Assistant Professor / Harvard Medical School
PESC: Stress-driven acceleration of epigenetic age and inflammation in transgender and gender diverse adults (TransESSENCE)
PESC: Stress-driven acceleration of epigenetic age and inflammation in transgender and gender diverse adults (TransESSENCE)
2021-2022 /
165 (total)
50 (1st/Sr)
 
Sanjay Divakaran, MD
Instructor / Harvard Medical School
REC-4: Skeletal Muscle Perfusion and Energetics in Patients with Symptomatic Peripheral Artery Disease. Joint Boston OAIC-Harvard Catalyst C-MERIT Awardee.
Dr. Divarkaran is an Instructor in Medicine in the Division of Cardiology, BWH. His research focuses on using perfusion and metabolic positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) to uncover changes in oxygen delivery and metabolism in older individuals with peripheral artery disease (PAD)7. Studying patients with PAD at rest and post-exercise with PET and MRS has the potential to help better phenotype patients with PAD and address critical gaps in knowledge regarding the pathophysiology of intermittent claudication. For the OAIC REC, he proposes to use PET, MRS, and omics technologies to study 10 older adults with PAD before and after endovascular revascularization procedures. He will perform novel pre- and post-exercise plasma biomarker discovery by measuring differential microRNA expression and targeted protein biomarkers. His mentors are Dr. Marcelo Di Carli, a world-expert in perfusion and metabolic PET imaging, and Dr. Mark Feinberg, Director of the Program of Cardiovascular RNA Biology at BWH. He will utilize the OAIC Functional Assessment, Preclinical Discovery, and Biostatistical Design and Analysis Cores.
2021-2022 /
41 (total)
12 (1st/Sr)
 
Timothy Anderson, MD
Instructor / Harvard Medical School
REC-1: Impact of intensifying older adults’ antihypertensive medication regimens at hospital discharge on home blood pressure and functional recovery.
Dr. Anderson is a general internist and Instructor in Medicine at Beth Israel Deaconess Medical Center (BIDMC). His prior research has analyzed large datasets to study clinical outcomes of older adults receiving changes to their chronic disease medications at hospital discharge4; this work is currently supported by a NIA GEMSSTAR Award. For the OIAC REC, he proposes to conduct a prospective cohort study of 90 community dwelling older adults hospitalized at BIDMC who experience elevated inpatient blood pressure (BP). He will assess the feasibility of recruiting these older adults at hospital discharge into a 3-month study during which they will complete home BP recordings and patient reported functional questionnaires. He will compare home BPs and functional recovery in patients who did and did not receive BP medication intensifications at hospital discharge. Completion of this proposal will allow Dr. Anderson to gain experience in prospective primary data collection. He will use the OAIC Functional Assessment and Biostatistical Design and Analysis Cores. His primary mentor is Dr. Edward Marcantonio, MD, SM, Associate Director of the OAIC REC.
2021-2022 /
32 (total)
20 (1st/Sr)
 
Clark DuMontier, MD
Geriatrician, Fellow / Harvard Medical School
REC-2: Integrating Feasible and Valid Functional Outcomes in Older Patients with Multiple Myeloma Undergoing Chemotherapy.
Dr. DuMontier is geriatrician and research fellow in the Division of Aging, Brigham and Women’s Hospital (BWH) focused on integrating geriatrics into oncology, with a focus on functional assessment5. Multiple myeloma is a disease of aging, with two-thirds of patients diagnosed after age 65. Improving function in older adults with cancer is a high priority for patients, yet functional outcomes in multiple myeloma remain understudied. The objective of his proposal is to compare the feasibility of several measures of function that are well-established in aging research but underutilized in myeloma practice. He will recruit 50 transplant-ineligible patients age = 75 with newly-diagnosed multiple myeloma who plan to undergo induction chemotherapy and collect several patient-reported measures of function at these patients’ initial appointment and monthly thereafter for six months while undergoing induction chemotherapy. The study will determine which measures of physical function are valid and feasible to be completed by older patients in busy oncology clinics. Dr. Dumontier’s primary research mentor is Dr. Jane Driver, MD, MPH, who co-directs the Older Adult Hematologic Malignancy Program at Dana-Farber. He will use the OAIC Functional Assessment and Biostatistical Design and Analysis Cores.
2021-2022 /
20 (total)
8 (1st/Sr)
 

Past Scholars
Jason Sanders, MD, Harvard Medical School (2020-2021)

PILOT/EXPLORATORY PROJECTS (6 Pilot Projects Listed)
1. Project Title: REC-2: Integrating Feasible and Valid Functional Outcomes in Older Patients with Multiple Myeloma Undergoing Chemotherapy.
  Leader: Clark DuMontier, MD
  Dr. DuMontier is geriatrician and research fellow in the Division of Aging, Brigham and Women’s Hospital (BWH) focused on integrating geriatrics into oncology, with a focus on functional assessment 5. Multiple myeloma is a disease of aging, with two-thirds of patients diagnosed after age 65. Improving function in older adults with cancer is a high priority for patients, yet functional outcomes in multiple myeloma remain understudied. The objective of his proposal is to compare the feasibility of several measures of function that are well-established in aging research but underutilized in myeloma practice. He will recruit 50 transplant-ineligible patients age 75 with newly-diagnosed multiple myeloma who plan to undergo induction chemotherapy and collect several patient-reported measures of function at these patients’ initial appointment and monthly thereafter for six months while undergoing induction chemotherapy. The study will determine which measures of physical function are valid and feasible to be completed by older patients in busy oncology clinics. Dr. Dumontier’s primary research mentor is Dr. Jane Driver, MD, MPH, who co-directs the Older Adult Hematologic Malignancy Program at Dana-Farber. He will use the OAIC Functional Assessment and Biostatistical Design and Analysis Cores
 
2. Project Title: REC-1: Impact of intensifying older adults’ antihypertensive medication regimens at hospital discharge on home blood pressure and functional recovery.
  Leader: Timothy S. Anderson, MD, MAS
  Dr. Anderson is a general internist and Instructor in Medicine at Beth Israel Deaconess Medical Center (BIDMC). His prior research has analyzed large datasets to study clinical outcomes of older adults receiving changes to their chronic disease medications at hospital discharge4; this work is currently supported by a NIA GEMSSTAR Award. For the OIAC REC, he proposes to conduct a prospective cohort study of 90 community dwelling older adults hospitalized at BIDMC who experience elevated inpatient blood pressure (BP). He will assess the feasibility of recruiting these older adults at hospital discharge into a 3-month study during which they will complete home BP recordings and patient reported functional questionnaires. He will compare home BPs and functional recovery in patients who did and did not receive BP medication intensifications at hospital discharge. Completion of this proposal will allow Dr. Anderson to gain experience in prospective primary data collection. He will use the OAIC Functional Assessment and Biostatistical Design and Analysis Cores. His primary mentor is Dr. Edward Marcantonio, MD, SM, Associate Director of the OAIC REC.
 
3. Project Title: PES-3: Stress-driven acceleration of epigenetic age and inflammation in transgender adults.
  Leader: PIs: Sari Reisner, ScD and Monty Montano, PhD
  Results from this study will establish whether there is a link between exposure to gender-related psychosocial stress and epigentic age (DNA methylation score) and inflamm-aging (e.g., elevated CRP, IL-6 levels); and whether epigentic age and inflammation are related to levels of physical function. The study outcomes will inform a followup R01 to evaluate a combined behavioral and exercise intervention to reverse accelerated aging and inflamm-aging due to life course exposure to psychosocial stressors.
 
4. Project Title: PES-1: Senescent cells from organs of older donors are transferred during transplantation and impair the physical exercise capacity of recipients.
  Leader: PI: Abdala El Khal, PhD and Stefan Tullius, MD, PhD
  The study will evaluate whether transplantation of younger organs into older recipients may delay aging and improve physical reserves. The study also hypothesizes that senolytics will improve organ quality, reduce the spread of senescent cells and improve physical function in older recipeints.
 
5. Project Title: REC-3: Contribution of Cellular Senescence to Delayed Wound Healing of Aging
  Leader: Daniel Roh, MD PhD
  Dr. Roh is an Assistant Professor of Surgery at Boston University School of Medicine in the field of Plastic and Reconstructive Surgery whose research focus is to discover new translational therapies that can reduce the burden of wounds for the older adult6. His project will test the hypothesis that senescent cell accumulation in aged skin contributes to impaired wound healing, and that reduction of these cells can be a valuable tool to improve wound healing in aged individuals. Using aged mice, he will determine the contribution of senescent cell accumulation to the impaired wound healing of aging. He will evaluate topical senolytic therapy as a potential treatment and determine the effect of reducing senescent cell burden on the impaired wound healing of aging. Rejuvenating and strengthening aged skin with senolytics could be used as a preventative measure to avoid wound complications in patients at risk for acute wounds that develop into chronic wounds. In addition, this project proposes to establish potential biomarkers of senescence and wound healing status. Dr. Roh’s mentors include LaDora Thompson PT PhD, Vladimir Botchkarev MD PhD, and Laura Niedernhofer, MD PhD. His project will utilize the Biostatistical Design and Analysis and the Preclinical Discovery Cores.
 
6. Project Title: REC-4: Skeletal Muscle Perfusion and Energetics in Patients with Symptomatic Peripheral Artery Disease. Joint Boston OAIC-Harvard Catalyst C-MERIT Awardee.
  Leader: Sanjay Divakaran, MD
  Dr. Divarkaran is an Instructor in Medicine in the Division of Cardiology, BWH. His research focuses on using perfusion and metabolic positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) to uncover changes in oxygen delivery and metabolism in older individuals with peripheral artery disease (PAD)7. Studying patients with PAD at rest and post-exercise with PET and MRS has the potential to help better phenotype patients with PAD and address critical gaps in knowledge regarding the pathophysiology of intermittent claudication. For the OAIC REC, he proposes to use PET, MRS, and omics technologies to study 10 older adults with PAD before and after endovascular revascularization procedures. He will perform novel pre- and post-exercise plasma biomarker discovery by measuring differential microRNA expression and targeted protein biomarkers. His mentors are Dr. Marcelo Di Carli, a world-expert in perfusion and metabolic PET imaging, and Dr. Mark Feinberg, Director of the Program of Cardiovascular RNA Biology at BWH. He will utilize the OAIC Functional Assessment, Preclinical Discovery, and Biostatistical Design and Analysis Cores.
 
DEVELOPMENT PROJECTS (3 Development Projects Listed)
1. Project Title: DP-2: Measuring intracellular NAD in skeletal muscle and brain using 7T magnetic resonance spectroscopy
  Leader: Alex Lin, PhD and Ravi Jasuja, PhD
  Core(s):
 

The use of 7T MR spectroscopy to measure intracellular NAD in skeletal muscle and brain is novel and will be of value to ongoing and planned studies of NAD activators.

 
2. Project Title: DP-3: A novel statistical method to compare interventions initiated over time.
  Leader: Karo Pencina, PhD, Co-I: Thomas Travison, PhD.
  Core(s):
 

A novel statistical method to compare treatments initiated over time to enable epidemiological assessment of treatment disparities in older adults.

 
3. Project Title: DP-1. Development of novel remote sensing technology to assess muscle performance in community dwelling older adults
  Leader: Roger A. Fielding, Tufts-HNRCA, Kieran F. Reid, Brigham and Women’s Hospital and Conor J. Walsh, Harvard University
  Core(s):
  This project will focus on the refinement of prototypes to collect data from the appropriate body segments during strength training and assessment, develop algorithms to appropriately interpret the sensor data, and refine an initial web application. Finally, we will validate and evaluate the technology with established gold-standard assessment measures of muscle strength, power, and fatigue in older adults. Aim 1. Wearable technology development. Previously, the Biodesign Lab developed a modular and wearable hardware system, which includes two Inertial Measurement Units (IMUs). Aim 2. Validation study: The prototype technology platform will be developed to capture sensor-based measures of muscle performance (muscle force, contractile velocity, power and fatigue). The reliability, reproducibility and instrumental validity of muscle performance measures will be quantitively assessed and directly compared to several gold-standard, laboratory-based assessments of muscle performance and physical function. Aim 3. Single participant longitudinal case study: One participant will train three times per week for 8 weeks in their home. Since the technology is not yet suitable for independent home use, a member of the research team will visit the participant’s home.
 
RESEARCH (4 Projects Listed)
1. Project Title: UNCOVERING MOLECULAR EFFECTORS OF MAMMALIAN AGING
  Leader(s): WAGERS, AMY JO
    HARVARD UNIVERSITY
    NIH DP1AG063419 / ( 2018 - 2023 )
  Core(s):
  Aging is the single largest risk factor for most chronic degenerative diseases, including cardiovascular,musculoskeletal and neurodegenerative dysfunctions, and age-associated diseases now represent
 
2. 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 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.
 
3. 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 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.
 
4. 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 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.
 
PUBLICATIONS
2022
  1. Virtual frailty assessment for older adults with hematologic malignancies.
    DuMontier C, Jaung T, Bahl NE, Manor B, Testa MA, Dieli-Conwright CM, Kim DH, Hshieh T, Driver JA, Abel GA
    Blood Adv, 2022 May 26
    pii: bloodadvances.2022007188. https://doi.org/10.1182/bloodadvances.2022007188 | PMID: 35616435
    Citations: | AltScore: NA
  2. A proinflammatory diet is associated with increased odds of frailty after 12-year follow-up in a cohort of adults.
    Millar CL, Dufour AB, Shivappa N, Habtemariam D, Murabito JM, Benjamin EJ, Hebert JR, Kiel DP, Hannan MT, Sahni S
    Am J Clin Nutr, 2022 Feb 9, 115(2): 334-343
    https://doi.org/10.1093/ajcn/nqab317 | PMID: 34558613 | PMCID: PMC8827080
    Citations: 1 | AltScore: 67.55
  3. Dairy food intake is not associated with spinal trabecular bone score in men and women: the Framingham Osteoporosis Study.
    Millar CL, Kiel DP, Hannan MT, Sahni S
    Nutr J, 2022 May 10, 21(1): 26
    https://doi.org/10.1186/s12937-022-00781-1 | PMID: 35538577 | PMCID: PMC9092785
    Citations: | AltScore: NA
  4. HIV and Aging in the Era of ART and COVID-19: Symposium Overview.
    Montano M, Landay A, Perkins M, Holstad M, Pallikkuth S, Pahwa S, HIV and Aging in the Era of ART and COVID-19 Inter-CFAR Symposium.
    J Acquir Immune Defic Syndr, 2022 Feb 1, 89(Suppl 1): S3-S9
    https://doi.org/10.1097/QAI.0000000000002837 | PMID: 35015739 | PMCID: PMC8751291
    Citations: | AltScore: NA
  5. Long-Term Aspirin Use and Self-Reported Walking Speed in Older Men: The Physicians' Health Study.
    Orkaby AR, Dufour AB, Yang L, Sesso HD, Gaziano JM, Djousse L, Driver JA, Travison TG
    J Frailty Aging, 2022, 11(1): 12-17
    https://doi.org/10.14283/jfa.2021.36 | PMID: 35122085 | PMCID: PMC8818085
    Citations: | AltScore: 5
  6. Social Characteristics, Health, and Mortality Among Male Centenarians Using Veterans Affairs (VA) Health Care.
    Quach LT, Cho K, Driver JA, Ward R, Spiro A, Dugan E, Gaziano MJ, Djousse L, Rudolph JL, Gagnon DR
    Res Aging, 2022 Feb, 44(2): 136-143
    https://doi.org/10.1177/01640275211000724 | PMID: 33779393
    Citations: | AltScore: NA
  7. Elevated skin senescence in young mice causes delayed wound healing.
    Samdavid Thanapaul RJR, Shvedova M, Shin GH, Crouch J, Roh DS
    Geroscience, 2022 Jun, 44(3): 1871-1878
    https://doi.org/10.1007/s11357-022-00551-1 | PMID: 35399134 | PMCID: PMC9213596
    Citations: | AltScore: 1.5
  8. Relation of Testosterone, Dihydrotestosterone, and Estradiol With Changes in Outcomes Measures in the Testosterone Trials.
    Stephens-Shields AJ, Snyder PJ, Ellenberg SS, Taylor L, Bhasin S
    J Clin Endocrinol Metab, 2022 Apr 19, 107(5): 1257-1269
    https://doi.org/10.1210/clinem/dgac028 | PMID: 35041751 | PMCID: PMC9016457
    Citations: | AltScore: 18.05
  9. Reduced Levels of NAD in Skeletal Muscle and Increased Physiologic Frailty Are Associated With Viral Coinfection in Asymptomatic Middle-Aged Adults.
    Tran T, Pencina KM, Schultz MB, Li Z, Ghattas C, Lau J, Sinclair DA, Montano M
    J Acquir Immune Defic Syndr, 2022 Feb 1, 89(Suppl 1): S15-S22
    https://doi.org/10.1097/QAI.0000000000002852 | PMID: 35015741 | PMCID: PMC8751286
    Citations: 1 | AltScore: 7.3
  10. Association of Myocardial Blood Flow Reserve With Adverse Left Ventricular Remodeling in Patients With Aortic Stenosis: The Microvascular Disease in Aortic Stenosis (MIDAS) Study.
    Zhou W, Sun YP, Divakaran S, Bajaj NS, Gupta A, Chandra A, Morgan V, Barrett L, Martell L, Bibbo CF, Hainer J, Lewis EF, Taqueti VR, Dorbala S, Blankstein R, Slomka P, Shah PB, Kaneko T, Adler DS, O'Gara P, Di Carli MF
    JAMA Cardiol, 2022 Jan 1, 7(1): 93-99
    https://doi.org/10.1001/jamacardio.2021.3396 | PMID: 34524397 | PMCID: PMC8444062
    Citations: 3 | AltScore: 13.7
 
2021
  1. Objective performance tests of cognition and physical function as part of a virtual geriatric assessment.
    Bahl NE, Magnavita ES, Hshieh T, Testa M, Kim D, Manor B, Driver JA, Abel GA, DuMontier C
    J Geriatr Oncol, 2021 Mar 29, 12(8): 1256-1258
    pii: S1879-4068(21)00083-7. https://doi.org/10.1016/j.jgo.2021.03.013 | PMID: 33795206 | PMCID: PMC8478966
    Citations: | AltScore: NA
  2. Impact of whey protein supplementation in a weight-loss intervention in rural dwelling adults: A feasibility study.
    Batsis JA, Petersen CL, Cook SB, Al-Nimr RI, Driesse T, Pidgeon D, Fielding R
    Clin Nutr ESPEN, 2021 Oct, 45: 426-432
    https://doi.org/10.1016/j.clnesp.2021.07.006 | PMID: 34620350 | PMCID: PMC8502229
    Citations: | AltScore: 4
  3. On Schr?dinger's Cat and Evaluation of Trials Disrupted by the Covid19 Pandemic: A Critical Appraisal.
    Cesari M, Calvani R, Canevelli M, Aprahamian I, de Souto Barreto P, Azzolino D, Fielding RA, Vanacore N, Inzitari M, Marzetti E
    J Frailty Aging, 2021, 10(4): 310-312
    https://doi.org/10.14283/jfa.2021.23 | PMID: 34549243 | PMCID: PMC8140750
    Citations: 3 | AltScore: 11.95
  4. FDG PET imaging in suspected cardiac sarcoidosis: diagnosis vs. prognosis.
    Divakaran S, Blankstein R
    J Nucl Cardiol, 2021 Oct 4
    https://doi.org/10.1007/s12350-021-02809-1 | PMID: 34608605 | PMCID: PMC8977394
    Citations: | AltScore: 1
  5. Coronary vasomotor dysfunction portends worse outcomes in patients with breast cancer.
    Divakaran S, Caron JP, Zhou W, Hainer J, Bibbo CF, Skali H, Taqueti VR, Dorbala S, Blankstein R, Groarke JD, Nohria A, Di Carli MF
    J Nucl Cardiol, 2021 Nov 24
    https://doi.org/10.1007/s12350-021-02825-1 | PMID: 34820770 | PMCID: PMC9126993
    Citations: 2 | AltScore: 5.95
  6. Supervised Exercise Therapy for Symptomatic Peripheral Artery Disease Among Medicare Beneficiaries Between 2017 and 2018: Participation Rates and Outcomes.
    Divakaran S, Carroll BJ, Chen S, Shen C, Bonaca MP, Secemsky EA
    Circ Cardiovasc Qual Outcomes, 2021 Aug, 14(8): e007953
    https://doi.org/10.1161/CIRCOUTCOMES.121.007953 | PMID: 34293930 | PMCID: PMC8373731
    Citations: 4 | AltScore: 19.5
  7. Decoding the link between heart failure and incident cancer.
    Divakaran S, Nohria A
    Eur Heart J, 2021 Aug 21, 42(32): 3060-3062
    https://doi.org/10.1093/eurheartj/ehab482 | PMID: 34389851
    Citations: 1 | AltScore: NA
  8. Muscle Cryoinjury and Quantification of Regenerating Myofibers in Mice.
    Endo Y, Karvar M, Sinha I
    Bio Protoc, 2021 Jun 5, 11(11): e4036
    https://doi.org/10.21769/BioProtoc.4036 | PMID: 34250203 | PMCID: PMC8250343
    Citations: | AltScore: 1.25
  9. Exercise-induced gene expression changes in skeletal muscle of old mice.
    Endo Y, Zhang Y, Olumi S, Karvar M, Argawal S, Neppl RL, Sinha I
    Genomics, 2021 Sep, 113(5): 2965-2976
    https://doi.org/10.1016/j.ygeno.2021.06.035 | PMID: 34214629 | PMCID: PMC8403630
    Citations: | AltScore: 6.7
  10. Effects of Low Doses of L-Carnitine Tartrate and Lipid Multi-Particulate Formulated Creatine Monohydrate on Muscle Protein Synthesis in Myoblasts and Bioavailability in Humans and Rodents.
    Fielding RA, Rivas D, Grosicki GJ, Ezzyat Y, Ceglia L, Price LL, Orhan C, Sahin K, Fowler K, White T, Durkee S, Kritsch K, Bellamine A
    Nutrients, 2021 Nov 9, 13(11):
    pii: 3985. https://doi.org/10.3390/nu13113985 | PMID: 34836240 | PMCID: PMC8625796
    Citations: | AltScore: NA
  11. Cardiac Sarcoidosis: When and How to Treat Inflammation.
    Giblin GT, Murphy L, Stewart GC, Desai AS, Di Carli MF, Blankstein R, Givertz MM, Tedrow UB, Sauer WH, Hunninghake GM, Dellaripa PF, Divakaran S, Lakdawala NK
    Card Fail Rev, 2021 Mar, 7: e17
    https://doi.org/10.15420/cfr.2021.16 | PMID: 34950507 | PMCID: PMC8674699
    Citations: | AltScore: 3.35
  12. Systemic and cerebral circulatory adjustment within the first 60?s after active standing: An integrative physiological view.
    Harms MPM, Finucane C, P?rez-Denia L, Juraschek SP, van Wijnen VK, Lipsitz LA, van Lieshout JJ, Wieling W
    Auton Neurosci, 2021 Mar, 231: 102756
    https://doi.org/10.1016/j.autneu.2020.102756 | PMID: 33385733 | PMCID: PMC8103784
    Citations: 7 | AltScore: 3.7
  13. Effect of Protein Intake on Visceral Abdominal Fat and Metabolic Biomarkers in Older Men with Functional Limitations: Results from a Randomized Clinical Trial.
    Huang G, Pencina K, Li Z, Apovian CM, Travison TG, Storer TW, Gagliano-Juc? T, Basaria S, Bhasin S
    J Gerontol A Biol Sci Med Sci, 2021 Jan 8, 76(6): 1084-1089
    pii: glab007. https://doi.org/10.1093/gerona/glab007 | PMID: 33417663 | PMCID: PMC8140050
    Citations: 3 | AltScore: 29.35
  14. Role of Exercise Treadmill Testing in?the?Assessment of Coronary Microvascular?Disease.
    Lopez DM, Divakaran S, Gupta A, Bajaj NS, Osborne MT, Zhou W, Hainer J, Bibbo CF, Skali H, Dorbala S, Taqueti VR, Blankstein R, Di Carli MF
    JACC Cardiovasc Imaging, 2021 Aug 11, 15(2): 312-321
    pii: S1936-878X(21)00567-2. https://doi.org/10.1016/j.jcmg.2021.07.013 | PMID: 34419395 | PMCID: PMC8831663
    Citations: 1 | AltScore: 29.25
  15. Immune health grades: Finding resilience in the COVID-19 pandemic and beyond.
    Marconi VC, Krishnan V, Ely EW, Montano M
    J Allergy Clin Immunol, 2021 Nov 2, 149(2): 565-568
    pii: S0091-6749(21)01683-3. https://doi.org/10.1016/j.jaci.2021.10.025 | PMID: 34740606 | PMCID: PMC8560746
    Citations: 1 | AltScore: 4.2
  16. Pressing Questions and Challenges in the HIV-1 and SARS-CoV-2 Syndemic.
    Montano M
    AIDS Res Hum Retroviruses, 2021 Aug, 37(8): 589-600
    https://doi.org/10.1089/AID.2021.0005 | PMID: 33587013 | PMCID: PMC8312028
    Citations: 2 | AltScore: 1.25
  17. Long-term effect of a 24-week multicomponent intervention on physical performance and frailty in community-dwelling older adults.
    Oh G, Lee H, Park CM, Jung HW, Lee E, Jang IY, Guralnik JM, Kim DH
    Age Ageing, 2021 Nov 10, 50(6): 2157-2166
    https://doi.org/10.1093/ageing/afab149 | PMID: 34351363 | PMCID: PMC8581390
    Citations: 4 | AltScore: 65.7
  18. Association Between Long-Term Aspirin Use and Frailty in Men: The Physicians' Health Study.
    Orkaby AR, Yang L, Dufour AB, Travison TG, Sesso HD, Driver JA, Djousse L, Gaziano JM
    J Gerontol A Biol Sci Med Sci, 2021 May 22, 76(6): 1077-1083
    https://doi.org/10.1093/gerona/glaa233 | PMID: 32918079 | PMCID: PMC8140052
    Citations: 2 | AltScore: 4.6
  19. A Selective Androgen Receptor Modulator (OPK-88004) in Prostate Cancer Survivors: A Randomized Trial.
    Pencina KM, Burnett AL, Storer TW, Guo W, Li Z, Kibel AS, Huang G, Blouin M, Berry DL, Basaria S, Bhasin S
    J Clin Endocrinol Metab, 2021 Jul 13, 106(8): 2171-2186
    https://doi.org/10.1210/clinem/dgab361 | PMID: 34019661 | PMCID: PMC8277210
    Citations: 1 | AltScore: 0.75
  20. Novel Roles of Follistatin/Myostatin in Transforming Growth Factor-? Signaling and Adipose Browning: Potential for Therapeutic Intervention in Obesity Related Metabolic Disorders.
    Pervin S, Reddy ST, Singh R
    Front Endocrinol (Lausanne), 2021, 12: 653179
    https://doi.org/10.3389/fendo.2021.653179 | PMID: 33897620 | PMCID: PMC8062757
    Citations: 4 | AltScore: 0.5
  21. Restored TDCA and valine levels imitate the effects of bariatric surgery.
    Quante M, Iske J, Heinbokel T, Desai BN, Cetina Biefer HR, Nian Y, Krenzien F, Matsunaga T, Uehara H, Maenosono R, Azuma H, Pratschke J, Falk CS, Lo T, Sheu E, Tavakkoli A, Abdi R, Perkins D, Alegre ML, Banks AS, Zhou H, Elkhal A, Tullius SG
    Elife, 2021 Jun 22, 10:
    pii: e62928. https://doi.org/10.7554/eLife.62928 | PMID: 34155969 | PMCID: PMC8257250
    Citations: 1 | AltScore: 7.45
  22. miR-19b-3p is associated with a diametric response to resistance exercise in older adults and regulates skeletal muscle anabolism via PTEN inhibition.
    Rivas DA, Peng F, Benard T, Ramos da Silva AS, Fielding RA, Margolis LM
    Am J Physiol Cell Physiol, 2021 Dec 1, 321(6): C977-C991
    https://doi.org/10.1152/ajpcell.00190.2021 | PMID: 34705586 | PMCID: PMC8714992
    Citations: 1 | AltScore: 6.5
  23. Total carotenoid intake is associated with reduced loss of grip strength and gait speed over time in adults: The Framingham Offspring Study.
    Sahni S, Dufour AB, Fielding RA, Newman AB, Kiel DP, Hannan MT, Jacques PF
    Am J Clin Nutr, 2021 Feb 2, 113(2): 437-445
    https://doi.org/10.1093/ajcn/nqaa288 | PMID: 33181830 | PMCID: PMC7851823
    Citations: 5 | AltScore: 19.95
  24. The effects of a physical and cognitive training intervention vs. physical training alone on older adults' physical activity: A randomized controlled trial with extended follow-up during COVID-19.
    Savikangas T, T?rm?kangas T, Tirkkonen A, Alen M, Fielding RA, Kivipelto M, Rantalainen T, Stigsdotter Neely A, Sipil? S
    PLoS One, 2021, 16(10): e0258559
    https://doi.org/10.1371/journal.pone.0258559 | PMID: 34644357 | PMCID: PMC8513828
    Citations: 1 | AltScore: 14.15
  25. Trajectories of Frailty in the 5 Years Prior to Death Among U.S. Veterans Born 1927-1934.
    Ward RE, Orkaby AR, Dumontier C, Charest B, Hawley CE, Yaksic E, Quach L, Kim DH, Gagnon DR, Gaziano JM, Cho K, Djousse L, Driver JA
    J Gerontol A Biol Sci Med Sci, 2021 Oct 13, 76(11): e347-e353
    https://doi.org/10.1093/gerona/glab196 | PMID: 34244759 | PMCID: PMC8825219
    Citations: 1 | AltScore: 8.1
  26. Impact of coronary artery calcium testing on patient management.
    Wu WY, Biery DW, Berman AN, Hsieh G, Divakaran S, Gupta S, Steigner ML, Aghayev A, Skali H, Polk DM, Plutzky J, Cannon CP, Di Carli MF, Blankstein R
    J Cardiovasc Comput Tomogr, 2021 Dec 17, 16(4): 303-308
    pii: S1934-5925(21)00481-0. https://doi.org/10.1016/j.jcct.2021.12.006 | PMID: 34998708 | PMCID: PMC9203593
    Citations: | AltScore: 37.3
  27. Effects of obesity and weight-loss surgery shift the microbiome and impact alloimmune responses.
    Zhou H, Tullius SG
    Curr Opin Organ Transplant, 2021 Dec 1, 26(6): 603-608
    https://doi.org/10.1097/MOT.0000000000000920 | PMID: 34714789 | PMCID: PMC8562884
    Citations: | AltScore: NA


EXTERNAL ADVISORY BOARD MEMBERS

Laura Niedernhofer, MD, PhD
University of Minnesota Medical School
Serving since 2016 (6 years)

Marco Pahor, MD
University of Florida Institute on Aging
Serving since 2016 (6 years)

Steven Kritchevsky, PhD
Wake Forest
Serving since 2016 (6 years)

Thomas Gill, MD
Yale University
Serving since 2016 (6 years)


RECOGNITION AND AWARDS (2021-2022)
Kei Ouchi, MD (2022)
  • Beeson Award
Tim Anderson, MD (2022)
  • Beeson Award

MINORITY RESEARCH

General Brief Description of Minority Activities:
Not defined.


Minority Trainee(s):
  • Rodrigo Valderrabano, MD, MSc., Assistant Professor of Medicine
    Dr. Valderrabano was recruited to Mass General Brigham from the University of Miami, Miami, FL, where he was an Assistant Professor of Medicine at the University of Miami, Miami, FL. Dr. Valderrabano received his medical degree from the Medical School in Puerto Rico and did a fellowship in Bone Health at Stanford University. Dr. Valderrabano is currently interested in muscle / bone dysfunction in people with diabetes and spinal cord injury. Integrating aging and outcomes of physical activity interventions is planned. Received a career development award in 2022

Minority Grant(s):