Diverse etiologies may account for physical disability in older adults. There is speculation that one common pathway, such as a loss of muscle mass and muscle strength, is frequently associated with the onset and progression of disability. The use of angiotensinconverting enzyme (ACE) inhibitors appears to reduce morbidity, mortality, hospital admission, and decline in physical function and exercise capacity in Congestive Heart Failure (CHF) patients. These therapeutic effects are attributed primarily to beneficial cardiovascular actions, but recent evidence suggests that ACE inhibitors may exert positive metabolic, mechanical and biochemical changes in the muscle and favorably modify markers of inflammation. In addition, genetic studies have suggested that healthy subjects with a reduced expression of ACE secondary to genetic polymorphism present greater muscle mass and strength in response to physical training. We hypothesize that the benefit of ACE inhibition on physical function extends to people without CHF. We propose to conduct an exploratory analysis using 3-year longitudinal data from the Health Aging and Body Composition (HABC) study to assess whether, among older adults without CHF, ACE inhibitors use is associated with a lower decline in muscle strength and muscle mass and, consequently, improved physical performance and decreased disability. In addition, we propose to explore underlying mechanisms responsible for these effects. In particular we aim to explore the interaction of ACE inhibitors with inflammatory markers and physical exercise. The HABC, a prospective cohort study, which enrolled 3,075 well-functioning participants aged 70-79 years, offers unique advantages, including the comprehensive phenotype definition of body composition, muscle performance, disability, the availability of inflammatory markers, and excellent retention of participants in the study. The study may provide evidence suggesting pharmacological benefits in preventing the decline in physical function among older adults as well as preliminary data for planning future studies aimed at preventing physical disability in the elderly. This project complements and extends other ongoing and planned clinical and basic research studies in our OAIC which address the same hypothesis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Center Core Grants (P30)
Project #
1P30AG021332-01
Application #
6686890
Study Section
Special Emphasis Panel (ZAG1)
Project Start
2002-09-30
Project End
2007-06-30
Budget Start
Budget End
Support Year
1
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Bhasin, Shalender; Gill, Thomas M; Reuben, David B et al. (2018) Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE): A Cluster-Randomized Pragmatic Trial of a Multifactorial Fall Injury Prevention Strategy: Design and Methods. J Gerontol A Biol Sci Med Sci 73:1053-1061
Lucas, Alexander R; Klepin, Heidi D; Porges, Stephen W et al. (2018) Mindfulness-Based Movement: A Polyvagal Perspective. Integr Cancer Ther 17:5-15
Wasson, Emily; Rosso, Andrea L; Santanasto, Adam J et al. (2018) Neural correlates of perceived physical and mental fatigability in older adults: A pilot study. Exp Gerontol 115:139-147
Wilson, Quentin N; Wells, Magan; Davis, Ashley T et al. (2018) Greater Microbial Translocation and Vulnerability to Metabolic Disease in Healthy Aged Female Monkeys. Sci Rep 8:11373
Kim, Sunghye; Miller, Michael E; Lin, Marina et al. (2018) Self- vs proxy-reported mobility using the mobility assessment tool-short form in elderly preoperative patients. Eur Rev Aging Phys Act 15:5
Anton, Stephen D; Moehl, Keelin; Donahoo, William T et al. (2018) Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring) 26:254-268
Datta, Rupak; Trentalange, Mark; Van Ness, Peter H et al. (2018) Serious adverse events of older adults in nursing home and community intervention trials. Contemp Clin Trials Commun 9:77-80
Mokhtari, Fatemeh; Rejeski, W Jack; Zhu, Yingying et al. (2018) Dynamic fMRI networks predict success in a behavioral weight loss program among older adults. Neuroimage 173:421-433
Justice, Jamie N; Ferrucci, Luigi; Newman, Anne B et al. (2018) A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup. Geroscience 40:419-436
Schoell, Samantha L; Beavers, Kristen M; Beavers, Daniel P et al. (2018) Prediction of lumbar vertebral body compressive strength of overweight and obese older adults using morphed subject-specific finite-element models to evaluate the effects of weight loss. Aging Clin Exp Res :

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