Wake Forest OAIC Overview P 30 AG 021332

Wake Forest OAIC Overview P 30 AG 021332

Sticht Center on Aging: Mission Promote the health and independence of older adults by fostering multi-disciplinary collaboration in basic and clinical research, research training, professional education and community outreach.

WFU OAIC: Theme and Aims Theme: Integrating pathways affecting physical function for new approaches to disability treatment and prevention. Aims: • Discover new common pathways contributing to age-related declines in physical function and disability; • Develop, evaluate and refine strategies for disability treatment and prevention; • Translate proven strategies beyond the traditional academic research environment; • Train the next generation of research leaders focused on disability treatment and prevention. Wake Forest School of Medicine

WFU OAIC Organizational Structure Leadership and Administrative Core (Kritchevsky / Kitzman) Research Career Development Core (Kritchevsky / Loeser) Pilot and Exploratory Studies Core (Kitzman / Register) Coordinating Center (High/ Miller) Governance Monthly Exectutive Committee meetings Annual External Advisory Committee Meeting Wake Forest School of Medicine Resource Cores Clinical Research Core (Williamson / Rejeski) Biostatistics and Research Information Systems Core (Miller / Ip) Integrative Biology Core (Nicklas / Delbono) Bio. Imaging Resource Core (Hundley / Carr)

WFU OAIC Integrated Conceptual Model Genes Comorbidity Modifiable Behaviors / Environment Total and Regional Adiposity Limitation Wake Forest School of Medicine Age Restriction Cognitive / Psychological Factors Skeletal Muscle Mass / Function Disability

Obesity / Adiposity and Function: Selected Findings Total Adiposity and Physical Function • Obesity: 1) predicts incident mobility disability more strongly than strength or muscle mass; 2) is as strong a risk factor functional decline as physical inactivity; and 3) blunts the inverse association between physical activity and function. Regional Adipose Tissue Deposition • Pericardial fat is associated with coronary atherosclerosis and the onset of acute coronary events independently of generalized measures of adiposity. • Intraperitoneal fat is associated with the thickening of the descending thoracic artery • Renal sinus fat is associated with refractory hypertension. • Increasing thigh intramuscular fat is associated with declining gait speed.

Weight Loss Interventions in Older Adults: Selected Findings Weight Loss and Exercise Interventions • Moderate weight loss improves physical function in obese and overweight older adults. • Fat mass loss is associated with gain in physical function with intentional weight loss. • The functional benefits of moderate weight loss add to those of aerobic or mixed aerobic and resistive exercise. Optimizing Weight Loss Strategies • Skeletal muscle loss during weight loss can be halved with concomitant resistive exercise or adequate protein intake. • Regained weight after intentional weight loss, has a higher (adverse) fat / lean ratio.

Long-term mortality in persons randomized to weight loss interventions. Adjusted HR (95%CI) TONE (n=585, 101 deaths) 0. 82 (0. 55 -1. 22)a Weight Loss: 4. 4 kg versus 0. 8 kg ADAPT (n=316, 43 deaths) 0. 49 (0. 26 -0. 93)b Weight Loss: 4. 5 kg versus 1. 5 kg Combined (n=901, 144 deaths) 0. 62 (0. 40 -0. 98)c 0. 50 1. 00 Favors Weight loss 1. 5 Favors Non. Weight loss a adjusted for age, gender, race, study site, CVD history, DBP, smoking status, randomization to low sodium intervention b adjusted for age, gender, CVD history, randomization to exercise intervention c adjusted for age, gender, race, CVD history, study (TONE or ADAPT) Shea MK et al. , AJCN 2011

Support Group – Diabetes support and education (n= 2502) ILI Group – 7% weight loss & 175 min physical activity per week (n=2514) Wake Forest School of Medicine

Selected On-going Trials Trial Population Groups Lifestyle Interventions and Independence for Elders High Disability Risk Exercise, Control Look AHEAD Movement and Mobility Ancillary Type II Diabetes Weight Loss + Exercise; Control Cooperative Lifestyle Intervention Program II Obese with CVD or Metabolic Syndrome Weight Loss, Weight Loss + Aerobic Ex; Weight Loss + Resistance Ex Study of the Effects of Caloric Heart Failure with Restriction and Exercise Training Preserved EF (SECRET) Aerobic Ex; Weight Loss; Aerobic Ex + Weight Loss; Control Strength Training for Arthritis Trial High Intensity Resistance Ex; Low Intensity Resistance Ex; Control Knee OA Loss of Fat Tissue and Obese & Sedentary Functional Response to Exercise in Older, Obese Adults Resistance Ex; Resistance + Weight Loss Investigating Fitness in the Elderly Aerobic Ex; Aerobic + Low Weight Loss; Aerobic + High Weight Loss Wake Forest School of Medicine Obese & Sedentary

Integrated Aging Studies Databank and Repository (IASDR) • Holds >135, 000 serum/plasma cryovials and >1260 DNA samples from >3100 research participants enrolled in 29 different OAIC supported studies as well as skeletal muscle, adipose, and cartilage samples • Extensive phenotyping: physical and cognitive function, QOL, body composition • Specific disorders commonly associated with physical disability in older persons: osteoarthritis, diabetes, chronic kidney disease, COPD, heart failure, obesity • Reference group of healthy, age and gender matched subjects (HEALTHY study) • Offered as OAIC resource: www. peppercenter-wfu. org/public/bio_materials. cfm Wake Forest School of Medicine

RCDC • Attract and develop scientists from a variety of backgrounds • Team-based mentoring paradigm • Close integration with the PEC and research support cores • Adding an Emerging Scholar track to develop promising candidates. Wake Forest School of Medicine

WF Pepper Scholars & Emerging Scholars • Kate Saul, Ph. D (Biomedical Engineering) o In Silico shoulder joint modeling to optimize rehabilitation • D. Clark Files, MD (Pulmonary and Critical Care Medicine) o Skeletal muscle dysfunction following acute lung injury in a murine model • Christina Hugenschmidt, Ph. D (Geriatrics) o Patterns of brain network connectivity as related to obesity and physical function • Anthony Molina, Ph. D (Geriatrics) o Mitochondrial function as it relates to mobility in obese older adults • Kathryn E. Callahan, MD (Geriatrics) o Physical and cognitive function as drivers of hospital readmissions • Valarie Wilson, MD (Geriatrics) o 25 (OH) D and age-related cognitive change in the Health ABC study Wake Forest School of Medicine

Pilot Studies Core • Translational, team-based projects with both basic and clinical research • Coordination with RCDC to ensure synergism • Annual RFA; merit-based review • Active fostering and monitoring of progress • 10 -fold return on investment (> $386 K / pilot) Wake Forest School of Medicine

Selected Pilot Projects • Youngmei Liu: Trancriptome and epigenome profiling before and after weight loss intervention in older persons • Denise Houston: Nutritional intervention to prevent weight regain and optimize body composition following caloric restriction • D. Clark Files: Effect of age on recovery from acute lung injury-induced skeletal muscle wasting Wake Forest School of Medicine

Research Dissemination • Functional assessment and exercise in older cancer patients (Klepin) • Functional assessment in pre-operative holding area to predict post-surgical complications (Kim and Groban) • Functional assessment to manage early discharge and reduce re-hospitalizations for Medicare patients with heart failure, pneumonia or MI. (Duncan) • Early mobility in the ICU to prevent post-discharge functional impairment (Morris) Wake Forest School of Medicine

Selected Community Based Programs

Specialized Collaborative Expertise • Clinical trials of novel interventions targeting physical function outcomes: • Conceptualization, design, implementation, and dissemination • Pilot study, single-site and multi-site • Participant recruitment, retention • Behavioral interventions • Animal models of muscle function and aging including non-human primate models • Development and utilization of novel quantitative imaging techniques to identify and modify specific phenotypes Wake Forest School of Medicine