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University of FloridaClaude D. Pepper Older Americans
Independence CenterMarco Pahor, MD
www.aging.ufl.edu
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UF Institute on Aging Mission
To serve as the major catalyst for developing interdisciplinary models and synergisms in the areas of research, education and health care across all Colleges and Departments at the University of Florida and its affiliates to improve the health, independence and quality of life of older adults
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Goals: “One stop shop”
• Interdisciplinary research focused on a common theme: “the etiology, prevention and rehabilitation of cognitive and physical disability”
• Career development and education• Cross-campus system of integrated state-
of-the-art health care for older persons
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Our strategy
To attract investigators from diverse social, behavioral, clinical and basic science disciplines towards research on aging that focuses on a common theme
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UF Institute on Aging in numbers 2007
• $43.5 million in extramural funds• 30 funded research projects• 60 funded investigators - 27 trainees• 11 partnering UF colleges• 20,000 sq. ft. core research and office space• 11 locations in Gainesville and beyond• >900 patient base
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Public Health & Health ProfessionsMedicine Nursing
UF Institute on Aging -Claude Pepper Older Americans
Independence Center
Shands Hospital
VA Hospital
GCRC
Institute on Aging
Cancer Center
Clinic Settings
Health Sciences Colleges
Clinical Facilities
VA GRECC
Liberal Arts& Sciences
Other Colleges
Fellows, House Staff, T-K trainees,VA, National Pool
Junior Scholars Candidates Pool
Health & Human Performance
Genetics Institute
Brain Institute
Research Facilities
Cancer Center
Pharmacy Dentistry
Interactions of the Institute on Aging and Pepper Center with UF colleges and other organizations
IFAS
EngineeringVeterinaryMedicine
Journalism and Communications
Public Health & Health ProfessionsMedicine Nursing
UF Institute on Aging -Claude Pepper Older Americans
Independence Center
Shands Hospital
VA Hospital
GCRC
Institute on Aging
Cancer Center
Clinic Settings
Health Sciences Colleges
Clinical Facilities
VA GRECC
Liberal Arts& Sciences
Other Colleges
Fellows, House Staff, T-K trainees,VA, National Pool
Junior Scholars Candidates Pool
Health & Human Performance
Genetics Institute
Brain Institute
Research Facilities
Cancer Center
Pharmacy Dentistry
Interactions of the Institute on Aging and Pepper Center with UF colleges and other organizations
IFAS
EngineeringVeterinaryMedicine
Journalism and Communications
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Claude Denson PepperPolitician, philanthropist and champion of the elderly
• Born in rural Alabama in 1900• Graduate University of Alabama• Graduate Harvard Law School• Set up practice in Perry, Florida in 1925 • 1929-30 Florida State House of Representatives• Elected to the U.S. Senate until 1951 • U.S. House of Representatives, 1962-89 • Chair of the House Select Committee on Aging in 1977 • In 1986 he established The Claude Pepper Foundation• Died in 1989
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Pepper Center Features Older Americans Independence Center (OAIC)
• NIH-NIA Center Grant• High national visibility • Core structure - overarching theme• Interdisciplinary research• Training future leaders
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Claude Pepper Older Americans Independence Centers (OAIC)
Funded by the National Institute on Aging
• Duke U• J Hopkins U• UCLA• U Florida• U Maryland
• U Michigan• U Pittsburgh• U Texas MB• Wake Forest U• Yale U
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UF Pepper Center 2007-2012
The theme Sarcopenia: prevention and
rehabilitation of disabilityis 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
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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
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Projected US population aged >65 years according to disability (IADL+ADL)
6.8 7.1 7.5 8.5 9.7 11 12
29.2 32.2 37.444
51.658.3
27.3
0
10
20
3040
50
60
70
80
2000 2005 2010 2015 2020 2025 2030
Mill
ion
Disabled Non disabled
Year
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Challenge to expand active life expectancy
Age (years)
%
Survival
0
50
0 10050
Active life
Active life freeof disability
100
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Co-morbid factorsCVD, COPD, cognitive disorders, depression, diabetes, osteoporosis,
osteoarthritis
Disability
ImpairmentFunctional limitation
SarcopeniaAdiposity
Behavioral factorsPhysical exercise - diet
GenesBiological factorsinflammation, hormones,
oxidative damage, anemia, renin-angiotensin system
Causal model of functional limitation and disability in aging
Social, economic & environ-
mental factors
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Clinical Research,Epidemiology
Dr. Pahor
Preclinical& Translational
ResearchDr. Scarpace
Dr. Carter
Genomics, Metabolism &Biomarkers,
Dr. Leeuwenburgh, Dr. Baker
Biostatistics, Data Management, Quality Control and
MethodologyDr. Daniels,
Dr. Shenkman
Leadership Dr. Pahor Ms. Crump
Recruitment, Adherence,
and RetentionDr. Marsiske
Research CareerDevelopment
Dr. BeythDr. Leeuwenburgh
Pilot and Exploratory StudiesDr. Shorr, Dr. Carter
Pepper Center Cores
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Leadership Core• Scientific leadership• Cohesive focus• Strategic planning• Organization and administrative operations• Review and evaluation• Tracking and monitoring of the research
and training program
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Research Career Development Core
• Develops careers of future research leaders in the area of aging and independence
• Develops multidisciplinary skills for translating across traditional boundaries of scientific disciplines
• Selects, tracks and monitors Pepper Center Junior Scholars
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Pilot and Exploratory Studies Core
• Supports research to acquire information needed to conduct future clinical and preclinical research studies in the areas of Pepper Center focus
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Clinical Research Core• Supports research in human subjects (controlled
trials, observational studies)• Selects and utilizes optimal measures • Studies the mechanisms contributing to changes in
walking• Conducts secondary analyses of existing studies• Develops interventions to improve physical function
and quality of life of older adults
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Pre-clinical Research Core
• Conducts mechanistic and intervention studies in animal models
• Results and hypotheses are translated and applied to clinical research studies
• Concepts on disability that are developed in the clinical arena are applied in animal models
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Biostatistics and Data Management Core
• Supports all research activities in the planning, implementation and analytical phases
• Develops and implements novel analytical methodologies
• Is responsible for data management and quality control
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Recruitment Core
• Supports recruitment of research study participants
• Promotes adherence and retention • Develops novel recruitment, retention and
adherence strategies with particular focus on minorities
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Genomics and Biomarkers Core
• Conducts studies on biomarkers and genetics of sarcopenia, physical function and disability
• Primary focus on mitochondrial energy utilization, inflammation, oxidative stress, and apoptosis
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Aerobic exercise
BP check
Taking a break during the walk
Outdoor walking
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Flexibilitystretching
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8.58.7
7.5 7.98.0
6
7
8
9
10
0 6 12
Sco
re
Physical activitySuccessful aging
P<0.001
mo moMeans estimated from repeated measures ANCOVA adjusted for gender, field center and baseline values
LIFE-Pilot study: SPPB score
J Gerontol Biol Sci Med Sci 2006;61:1157
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LIFE Pilot study: Cumulative hazard of time until major mobility disability
SA 211 PA 213
Number at risk
210213
191191
107125
2433
SA 0 PA 0
Cumulativeendpoints
1315
2823
3324
3426
SA= Successful agingPA= Physical Activity
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Primary: Major mobility disability defined as incapacity to walk 400 m
Secondary: • Cognitive function• Serious fall injuries• Persistent mobility disability, mobility disability/death • Disability in activities of daily living (ADLS)• Cardiovascular events• Nursing home/hospital admissions • HRQL (depression, sleep, stress, life satisfaction) • Cost-effectiveness• Mild cognitive impairment/dementia
LIFE main studyOutcomes
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LIFE main study Field Centers
CACO
LA FL
ILIN
NC
PACT
MA
N = 2,000 - Average Follow-up 4.5 yrs
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Grip Strength Meter
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AP
EarlyAutophagosome
Late Autophagosome
AutolysosomeLysosome
Rough EndoplasmicReticulum
AP
APAP
Rapamycin3MAWortmannin
LY294002
PI3 KinaseBeclin
mTorP70 S6 Kinase
Regulation of MacroautophagyAutophagy: housekeeping process through which damaged cellular constituents, such as dysfunctional mitochondria, are Removed.
Phosphatase 2A Okadaic AcidCalyculin AMicrocystin-LR
hATG7hATG9hATG8
hATG13
Ceramide2,3-Butanedione
monoxime
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young old
20X
10X
27 yr-old 73 yr-old
20X
10X
ApoptosisTUNELPositiveNuclei
Muscle cross-sections of vastus lateralis
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Pepper Center Supported External Grants• Physical Exercise to Prevent Disability - LIFE
Study, Dr. Pahor• The Epidemiology of Stress and the Metabolic
Syndrome, Dr. Pahor• ACE Inhibition and Physical Performance in Aged
Rats, Dr. Carter• Leptin resistance: mechanism underlying age-
related obesity, Dr. Scarpace• Apoptosis and life-long caloric restriction, Dr.
Leeuwenburgh
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Pepper Center Supported Pilot and Research Development Projects
• Autophagy and Sarcopenia in a Transgenic Mouse Model, Dr. Wohlgemuth
• Longitudinal Examination of Physical Performance, Dr. Daniels
• Skeletal Muscle Apoptosis and Physical Performance, Dr. Leeuwenburgh
• Leptin Inhibition, Blood Flow and Sarcopenia, Dr. Tümer
• A Network Based Analysis of Systemic Inflammation, Dr. Borsa
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Pepper Center Supported Pilot and Research Development Projects
• ACE inhibition and muscle quality Dr. Carter• Biological Effects of Weight Loss and Exercise in
Elders, Dr. Perri• Physical Exercise, Inflammation and Oxidative
Damage Dr. Cesari
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Our LeadersM. Pahor, MDH. Baker, PhDR. Beyth, MDL. Crump, MPHM. Daniels, PhD C. Leeuwenburgh, PhDM. Marsiske, PhDM. Perri, PhDP. Scarpace, PhDE. Shenkman, PhDR. Shorr, MD
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Pepper Junior Scholars Our Leaders of Tomorrow
S. Anton, PhDM. Bautista, MDM. Cesari, MD, PhD S. Kwon, PhD, RPh T. Manini, PhDE. Marzetti, MD, PhDB. Rahim-Williams, PhDS. Wohlgemuth, PhD