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