1. University of Florida Institute on Aging Claude D. Pepper Older Americans Independence Center Marco Pahor, MD www.aging.ufl.edu

2. 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

3. 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

5. 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

6. Public Health & Health Prof. MedicineNursing Pepper Center Shands Hospital VA Hospital CTSI Cognitive Aging Health Sciences Colleges VA GRECC Liberal Arts & Sciences Other Colleges Trainees Fellows, Residents, T-K trainees, Junior Faculty, Study Coordinators, Students Health & Human Performance Genetics Institute Brain Institute Institutes & Centers Cancer Center PharmacyDentistry Interactions of the Pepper Center with Colleges, Institutes, Centers & Other Organizations IFAS Engineering Veterinary Medicine Journalism & Communicat. Law Fine Arts Emerging Pathogens Inst. Hospitals Community Partners Corporate Partners

7. Institute on Aging Clinical Translational Research Building – NIH C06RR029852

8. Institute on Aging Health Promotion Research Center

9. UF Institute on Aging - Orlando Lake Nona Academic & Research Center

12. Major Phase 3 randomized controlled trials with disability outcomes in older persons The Life Study The TTrial ASPREE

14. Active Clinical Pilot Studies Study Name (Sponsor) PIBrief Description/ Targeted PopulationStage Think-2-Walk (Pepper) ClarkThe 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 Initiated 101 Contacts: 40 SV1s scheduled Apoptosis (Pepper) LeeuwenburghThis 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) NayfieldThe 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) DotsonThis 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

15. 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.

16. Pending/Emerging Clinical Studies Study Name (Sponsor) PIBrief Description/ Targeted PopulationStage Regeneron Trial Maninihuman monoclonal antibody for inhibiting myostatin that leads to muscle growth Regeneron preparing protocol CIRT (NIH)AntonLow-dose methotrexate to prevention of cardiovascular events in post-MI, metabolic impaired individuals Investigator Meeting Feb 1 st. Mind (Pepper)BufordDevelopment study to investigate relationship of central and peripheral nervous system function with overall physical function IRB Development Sanofi Inc. contract ManiniSecondary 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) ManiniNIH 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 ) CohenCreation of a database for metabolic, vascular, and functional neuroimages of aging brain RAC/IRB submissions

17. 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)

18. 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

19. 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.genes Terada. Laboratory Investigation (2011) 91, 972–977

20. 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.

21. 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)

22. 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 1/3 rd dead within one year. Overall Mortality Sespsis patients 20% Elderly Mortality 40%  Majority will have Cognitive and Functional Impairments in survivors

23. 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.

24. 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

25. 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

26. 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