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University of Florida Institute on AgingClaude D. Pepper Older Americans
Independence Center Marco Pahor, MD
www.aging.ufl.edu
UF Pepper Center 2007-2017
The theme Sarcopenia and prevention of disability
is being pursued using an interdisciplinary approach that traverses the entire spectrum of biomedical investigation, including molecular biology, animal studies, clinical research, behavioral sciences, epidemiology and health services
UF Pepper Center Mission
• To assess the risk factors and better understand the biological mechanisms of physical disability in older adults
• To develop and test effective prevention and rehabilitation therapies
• To train future leaders and researchers in the arena of aging and disability
Organizational Chart
Clinical TranslationsResearch,
Dr. Anton, Dr. Pahor
Metabolism &Biomarkers,
Dr. Leeuwenburgh
Biostatistics, Data Management, Quality
Control and MethodologyDr. Doss
Leadership and Administration -Dr. Pahor
Ms. Crump
Recruitment, Adherence, and RetentionDr. Marsiske
Research CareerDevelopment,
Dr. Leeuwenburgh
Pilot and Exploratory Studies
Dr. Carter
Dept. of Aging And Geriatric Research
Dr. Pahor
Management and Development Cores Resource Cores
VA GRECCDr. Shorr
Pepper Center
Cognitive Aging and Memory Clinical
Translational Research Program Dr. Cohen
University of Florida Institute on Aging OAIC
in numbers – 2007 - 2013
• 55 active research projects• 68 completed research projects • 15 pending grants• 50 funded investigators at 16 institutions• 45 trainees• 13 partnering UF colleges• 54,000 sq. ft. of office, research, clinical space
Public Health & Health Prof.
Medicine Nursing
Pepper Center
Shands Hospital
VA Hospital
CTSI
CognitiveAging
Health Sciences Colleges
VA GRECC
Liberal Arts& Sciences
Other Colleges
TraineesFellows, Residents, T-K trainees, Junior
Faculty, Study Coordinators, Students
Health & Human Performance
Genetics Institute
Brain Institute
Institutes & Centers
Cancer Center
Pharmacy Dentistry
Interactions of the Pepper Center with Colleges, Institutes, Centers & Other Organizations
IFAS
EngineeringVeterinaryMedicine
Journalism & Communicat.
LawFine Arts
Emerging Pathogens Inst.
Hospitals
Community Partners
CorporatePartners
Institute on Aging Clinical TranslationalResearch Building – NIH C06RR029852
Institute on Aging Health Promotion Research Center
UF Institute on Aging - OrlandoLake Nona Academic & Research Center
Biologyneural transmission, hormones,
proteolysis, autophagy, apoptosis, satellite cells,
inflammation, oxidative stress, energy production, blood flow
Body (physiological) functions
& Body structure
Aging
Diseasemetabolic, pulmonary,
vascular, immune, organ-specific
Activity limitationsDifficulties in executing tasks
DynapeniaLoss of muscle strength
Environmental Personal factors
ParticipationIn life situations
SarcopeniaMuscle atrophy &
intramuscular adipose
Independence
Healthcare cost
Caretaker Stress
Sarcopenia in the context of the International Classification of Function (ICF) model
Protein Synthesis
Apoptosis
Regeneration
Mitochondrial Dysfunction/ Oxidative Stress
Pro-Inflammatory Cytokines
Catabolic Hormones
Anabolic Hormones/
Growth Factors
Myofibrillarprotein
Myocyte Loss
Perfusion/Matrix
Remodeling
Amino Acid Availability
Hypoxic diseases
PAD
Physicalinactivity
Obesity
Obesity
ObesityLiver FailureCKD
PAD
Anabolic Hormones/
Growth Factors
Under-Nutrition
Diabetes
DiabetesObesityCOPD?
Diabetes
CKD
Liver FailureHypoxic diseases?
HIV/AIDS
Under-NutritionLiver Failure
DiabetesCancer-anorexia
-
-
-
HIV/AIDS
DiabetesCancer
Cancer?
+
Denervation
DiabetesPADHypoxic diseases
Proteolysis
Pro-Inflammatory Cytokines
-
-
+ ++
+
Denervation
CKDLiver Failure?
Sarcopenia
Sarcopenia, Disease and behaviors
Major Phase 3 randomized controlled trials with disability outcomes in older persons
• The Life Study
• The TTrial
• ASPREE
Active Clinical Pilot StudiesStudy Name
(Sponsor)PI Brief Description/ Targeted Population Stage
Think-2-Walk(Pepper)
Clark The two primary aims are: (1) determine whether peripheral sensory impairment increases the cortical demands of walking, and (2) whether increased cortical demands of walking reduces mobility function in older adults.
Recruitment Initiated101 Contacts: 40 SV1s scheduled
Apoptosis(Pepper)
Leeuwenburgh This study is investigating the role of apoptosis in contributing to sarcopenia and physical impairment in older adults.
Long-term follow-up
“Iatrogenic” Disability
(IDR) Project (CTSI)
Nayfield The Integrated Data Repository (IDR) aggregates data from various clinical and administrative information systems. This study will use the IDR to examine comorbidity indices, physical function, and “Iatrogenic disability” in patients hospitalized within the Shands hospital network.
Dataset developed and initial analyses underway
Exercise for Depression:The PAMM
Study(McKnight)
Dotson This project is testing whether aerobic exercise can improve cognitive and daily functioning of individuals with depression, and is using fMRI to explore potential mechanisms for hypothesized effects.
Recruitment/Intervention Initiated
Automaticity of walking: Age-related impairment and functional implications (Clark)
• To determine if peripheral sensory impairment increases cortical demand of walking and if increased cortical demand of walking reduces mobility function.
• Test the hypothesis that electromyographic (EMG) measures are more sensitive than gait parameters to determine cortical demand using a dual-tasking paradigm in older adults.
Pending/Emerging Clinical StudiesStudy Name
(Sponsor)PI Brief Description/ Targeted Population Stage
Regeneron Trial
Manini human monoclonal antibody for inhibiting myostatin that leads to muscle growth
Regeneron preparing protocol
CIRT (NIH) Anton Low-dose methotrexate to prevention of cardiovascular events in post-MI, metabolic impaired individuals
Investigator Meeting Feb 1st.
Mind (Pepper) Buford Development study to investigate relationship of central and peripheral nervous system function with overall physical function
IRB Development
Sanofi Inc. contract
Manini Secondary data analyses using existing data (non-human subjects) to identify cohorts for sarcopenia research
Conference call with Sonofi on 1-17-13
Chores XL (NIH)
Manini NIH R01 to test the hypothesis that aging is associated with a difference in the metabolic cost of doing exercise and lifestyle activities
NIH R01 – Council meeting on 1-29-13
Neuroimaging & Aging Brain (McKnight )
Cohen Creation of a database for metabolic, vascular, and functional neuroimages of aging brain
RAC/IRB submissions
Pepper Junior Scholars and Affiliate Pepper Scholars
• S. Someya Aging & Geriatric Research (9% RO1 Age-related hearing loss NIDCD) • K. Sibille, Community Dentistry (score 24 K-Award) (pain, OA, telomere biology)• D. Clark, Brain Rehabilitation Research Center, VA (VA Career Dev. Award)• A. Judge, Physical Therapy (RO1 funded on Basic Muscle Biology, not Aging, yet)• V. Dotson, Clinical & Health Psychology, Minority Supplement Funded/R21 pending• T. Buford, Aging & Geriatric Research (AHA and ADA grants submitted) • AM Joseph, Aging & Geriatric Research (Pepper Pilot Grant Funded)
• Affiliated Scholars• Silvia Tornaletti (Pepper Pilot Grant funded)• Phil Efron (Pepper Pilot Grant funded)• Natalie Ebner (Department of Psychology) (Submitting RO1 in response to RFA)• Mark Wallet (Department of Pathology, Immunology and Laboratory Medicine)• Peter Adhihetty (Department of Applied Physiology)
RCDC Activities-Roundtable Discussion (Academic Topics/ Grant Review) Combined with CTSI Scholars
-Semi-Annual Discussion on Academic Progress
-regular mentee/mentor committee meetings & formal feedback
-Seminar Series
-Workshops
Grant Review
Specialty Area Workshops
-Travel and Pilot Grant Support
Induced pluripotent stem cells (iPSCs): potential model to study mechanisms of human aging (Joseph, PhD and Terada, PhD)
iPSCs are a type of pluripotent stem cell artificially derived from a non-pluripotent cell - typically an adult somatic cell- by inducing a "forced" expression of specific genes.
Terada. Laboratory Investigation (2011) 91, 972–977
Continue: induced pluripotent stem cell (iPSC) study
• Establishment and characterization of human iPS cells for ES cell properties including stem cell markers, self-renewal, and pluripotency
• In vitro differentiation of muscle cells from human iPS cells.
• Determine the mechanisms of mitochondrial/autophagy alterations of iPS cells derived from individuals of disparate ages.
• The present project aims at identifying molecular mechanisms associated with the age-related features of sarcopenia by studying the relation of mitochondrial DNA stability with DNA repair efficiency and TFAM binding.
• We will investigate changes with declining physical function
Role of mitochondrial DNA repair in aging and sarcopenia (Silvia Tornaletti, PhD)
Sepsis/Trauma in the Elderly (Efron, Scientist and ICU MD)
Prolonged ICU stays and Manageable Organ Dysfunctions Recurrent Infections (Hits) and Persistent Acute Phase Response & Decreased LymphocytesDecreased Lean Body Mass – a Wasting Disease and Poor Wound HealingTransfer to LTACs for Indolent DeathsOlder Adults 25% discharged to SNFs and 1/3rd dead within one year. Overall Mortality Sespsis patients 20% Elderly Mortality 40% Majority will have Cognitive and Functional Impairments in survivors
Immune Mechanisms in the Elderly in Response to Severe Sepsis and Trauma. Animal Models Needed to Understand
Trauma/Sepsis syndrome in the elderly
• Characterize the emergency myelopoietic response during severe sepsis and severe polytrauma in the aged versus the young adult mouse.
• Examine whether increased dysregulation and delay in the emergency myelopoiesis response after sepsis or trauma is responsible, in part, for the immune suppression that leads to increased susceptibility and/or mortality to secondary infections in the elderly as compared to the young.
Future Directions
•Impact of cognition, memory and pain on physical function and sarcopenia
•Mitochondrial function•Pharmacological, nutritional and behavioral interventions to improve/maintain physical and cognitive function (LIFE-Extension Study, LIFE-ARISE prevention of AD, inflammation, vitamin D)
•Multimodality intervention studies
Our OAIC LeadersM. Pahor, MDS. Anton, PhDC. Carter, PhDR. Cohen, PhDL. Crump, MPHH. Doss, PhD C. Leeuwenburgh, PhDT. Manini, PhDM. Marsiske, PhDS. Nayfield MD
Pepper Junior Scholars Our Leaders of Tomorrow
D. Clark, PhDT. Buford, PhDV. Dotson, PhDA. Joseph, PhDA. Judge, PhDK. Sibille, PhDS. Someya, PhD