University of Florida Institute on Aging
Claude 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
Management and
Resource Cores
Development Cores
Pepper Center
Leadership and
Administration -Dr. Pahor
Ms. Crump
Research Career
Development,
Dr. Leeuwenburgh
Pilot and
Exploratory Studies
Dr. Carter
Dept. of Aging
And Geriatric Research
Dr. Pahor
VA GRECC
Dr. Shorr
Clinical Translations
Research,
Dr. Anton, Dr. Pahor
Metabolism &
Biomarkers,
Dr. Leeuwenburgh
Biostatistics, Data
Management, Quality
Control and Methodology
Dr. Doss
Recruitment, Adherence,
and Retention
Dr. Marsiske
Cognitive Aging and
Memory Clinical
Translational Research
Program Dr. Cohen
University of Florida Institute on Aging
OAIC
in numbers – 2007 - 2013
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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
Interactions of the Pepper Center with Colleges,
Institutes, Centers & Other Organizations
Health Sciences Colleges
Medicine
Public Health
& Health Prof.
Pharmacy
Dentistry
Other Colleges
Nursing
Veterinary
Medicine
Liberal Arts
& Sciences
Health & Human
Performance
Journalism &
Communicat.
Engineering
Institutes & Centers
Law
Fine
Arts
Hospitals
Cognitive
Aging
Shands
Hospital
CTSI
Genetics
Institute
IFAS
Pepper Center
VA
Hospital
Cancer Center
Brain Institute
Emerging
Pathogens Inst.
VA GRECC
Trainees
Fellows, Residents,
T-K trainees, Junior
Faculty, Study
Coordinators, Students
Community
Partners
Corporate
Partners
Institute on Aging Clinical Translational
Research Building – NIH C06RR029852
Institute on Aging
Health Promotion Research Center
UF Institute on Aging - Orlando
Lake Nona Academic & Research Center
Sarcopenia in the context of the International Classification of Function (ICF) model
Biology
neural transmission, hormones,
proteolysis, autophagy,
apoptosis, satellite cells,
inflammation, oxidative stress,
energy production, blood flow
Body (physiological)
functions
&
Body structure
Disease
Aging
metabolic,
pulmonary,
vascular, immune,
organ-specific
Environmental
 Healthcare cost
Sarcopenia
Muscle atrophy &
intramuscular adipose
 Caretaker Stress
Dynapenia
 Independence
Loss of muscle strength
Activity limitations
Difficulties in executing tasks
Participation
In life situations
Personal factors
PAD
Diabetes
Obesity
CKD
Liver Failure?
Cancer?
Sarcopenia,
Disease and behaviors
Diabetes
Obesity
Hypoxic diseases
CKD
Liver Failure
Cancer
HIV/AIDS
Mitochondrial Dysfunction/
Oxidative Stress +
+
Pro-Inflammatory
Cytokines
+
Apoptosis
UnderNutrition
+
Pro-Inflammatory
Cytokines
Myofibrillar
protein
+
Catabolic
Hormones
Obesity
Proteolysis
Sarcopenia
PAD
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Perfusion/
Matrix
Remodeling
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Regeneration
Diabetes
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CKD
HIV/AIDS
Liver Failure
Hypoxic diseases?
Anabolic
Hormones/
Growth
Factors
Denervation
PAD
Hypoxic diseases
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Myocyte
Loss
Protein
Synthesis
Amino Acid
Availability
Diabetes
Cancer-anorexia
Under-Nutrition
Liver Failure
Anabolic
Hormones/
Growth
Factors
Physical
inactivity
Diabetes
Obesity
COPD?
Denervation
Diabetes
Major Phase 3 randomized controlled trials
with disability outcomes in older persons
• The Life Study
• The TTrial
• ASPREE
Active Clinical Pilot Studies
Study Name
(Sponsor)
PI
Brief Description/ Targeted Population
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.
Apoptosis
(Pepper)
Leeuwenburgh This study is investigating the role of apoptosis in
contributing to sarcopenia and physical impairment in
older adults.
Stage
Recruitment Initiated
101 Contacts: 40
SV1s scheduled
Long-term follow-up
“Iatrogenic”
Disability
(IDR) Project
(CTSI)
Nayfield
The Integrated Data Repository (IDR) aggregates
Dataset developed
data from various clinical and administrative
and initial analyses
information systems. This study will use the IDR to
underway
examine comorbidity indices, physical function, and
“Iatrogenic disability” in patients hospitalized within the
Shands hospital network.
Exercise for
Depression:
The PAMM
Study
(McKnight)
Dotson
This project is testing whether aerobic exercise can
Recruitment/
improve cognitive and daily functioning of individuals Intervention Initiated
with depression, and is using fMRI to explore potential
mechanisms for hypothesized effects.
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 Studies
Study Name
(Sponsor)
Regeneron
Trial
CIRT (NIH)
PI
Brief Description/ Targeted Population
Manini human monoclonal antibody for inhibiting
myostatin that leads to muscle growth
Anton Low-dose methotrexate to prevention of
cardiovascular events in post-MI, metabolic
impaired individuals
Mind (Pepper) Buford Development study to investigate relationship of
central and peripheral nervous system function
with overall physical function
Sanofi Inc. Manini Secondary data analyses using existing data (noncontract
human subjects) to identify cohorts for sarcopenia
research
Chores XL Manini NIH R01 to test the hypothesis that aging is
(NIH)
associated with a difference in the metabolic cost
of doing exercise and lifestyle activities
Neuroimaging Cohen Creation of a database for metabolic, vascular,
& Aging Brain
and functional neuroimages of aging brain
(McKnight )
Stage
Regeneron
preparing protocol
Investigator Meeting
Feb 1st.
IRB Development
Conference call with
Sonofi on 1-17-13
NIH R01 –
Council meeting on
1-29-13
RAC/IRB
submissions
Pepper Junior Scholars and
Affiliate Pepper Scholars
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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)
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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, selfrenewal, 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.
Role of mitochondrial DNA repair in aging and sarcopenia
(Silvia Tornaletti, PhD)
•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
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 Lymphocytes
Decreased Lean Body Mass – a Wasting Disease and Poor Wound Healing
Transfer to LTACs for Indolent Deaths
Older 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 Leaders
M. Pahor, MD
S. Anton, PhD
C. Carter, PhD
R. Cohen, PhD
L. Crump, MPH
H. Doss, PhD
C. Leeuwenburgh, PhD
T. Manini, PhD
M. Marsiske, PhD
S. Nayfield MD
Pepper Junior Scholars
Our Leaders of Tomorrow
D. Clark, PhD
T. Buford, PhD
V. Dotson, PhD
A. Joseph, PhD
A. Judge, PhD
K. Sibille, PhD
S. Someya, PhD