Calorie restriction (CR) is known to extend the lifespan of rodents and several ?lower? species, and to improve surrogate markers for longevity and mortality in rhesus monkeys. There is, however, a paucity of reliable information on whether this is the case in humans as well. In response to a specific RFA from the NIA for descriptive experiments to address this issue, we propose a controlled, single-blinded study of several adaptive responses pertinent to this question in overweight volunteers imposed an initial 25% negative energy balance for two years by CR alone or by CR with additional physical activity. These responses include changes in energy metabolism, surrogate markers of oxidative stress and risks for cardiovascular disease and type-2 diabetes mellitus, neuroendocrine functions and autonomic nervous system activity, expression of candidate genes involved in energy metabolism, oxidative stress and longevity, and quality of life and physical fitness. In addition to descriptive information, we will test the hypotheses that CR with weight loss and maintenance of energy balance at a new body weight: 1. Lowers absolute and relative rates of energy expenditure and body temperature and decreases evidence of tissue oxidative stress. 2. Improves surrogate markers for cardiovascular disease and type-2 diabetes mellitus. 3. Affects the diurnal secretion of leptin leading to adaptations in the neuroendocine and autonomic nervous system enhance soma maintenance. 4. Alters the expression of genes involved in energy/protein metabolism, the production and clearance of reactive species, and ?longevity? genes in a fashion consistent with animal models of CR. 5. Improves the quality of life and metabolic fitness. A multidisciplinary team, including physiologists, behavioral psychologists, endocrinologists, molecular biologists and geneticists will conduct this study.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AG020478-06
Application #
7198083
Study Section
Special Emphasis Panel (ZRG1-GRM (04))
Program Officer
Romashkan, Sergei
Project Start
2002-03-15
Project End
2009-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
6
Fiscal Year
2007
Total Cost
$1,678,725
Indirect Cost
Name
Lsu Pennington Biomedical Research Center
Department
Type
Organized Research Units
DUNS #
611012324
City
Baton Rouge
State
LA
Country
United States
Zip Code
70808
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Racette, Susan B; Rochon, James; Uhrich, Mary L et al. (2017) Effects of Two Years of Calorie Restriction on Aerobic Capacity and Muscle Strength. Med Sci Sports Exerc 49:2240-2249
Sparks, Lauren M; Redman, Leanne M; Conley, Kevin E et al. (2017) Effects of 12 Months of Caloric Restriction on Muscle Mitochondrial Function in Healthy Individuals. J Clin Endocrinol Metab 102:111-121
Das, Sai Krupa; Roberts, Susan B; Bhapkar, Manjushri V et al. (2017) Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans. Am J Clin Nutr 105:913-927
Marlatt, Kara L; Redman, Leanne M; Burton, Jeff H et al. (2017) Persistence of weight loss and acquired behaviors 2 y after stopping a 2-y calorie restriction intervention. Am J Clin Nutr 105:928-935
Most, Jasper; Tosti, Valeria; Redman, Leanne M et al. (2017) Calorie restriction in humans: An update. Ageing Res Rev 39:36-45
Villareal, Dennis T; Fontana, Luigi; Das, Sai Krupa et al. (2016) Effect of Two-Year Caloric Restriction on Bone Metabolism and Bone Mineral Density in Non-Obese Younger Adults: A Randomized Clinical Trial. J Bone Miner Res 31:40-51
Kraus, William E; Pieper, Carl F; Huffman, Kim M et al. (2016) Association of Plasma Small-Molecule Intermediate Metabolites With Age and Body Mass Index Across Six Diverse Study Populations. J Gerontol A Biol Sci Med Sci 71:1507-1513
Rochon, James; Bhapkar, Manjushri; Pieper, Carl F et al. (2016) Application of the Marginal Structural Model to Account for Suboptimal Adherence in a Randomized Controlled Trial. Contemp Clin Trials Commun 4:222-228
Meydani, Simin N; Das, Sai K; Pieper, Carl F et al. (2016) Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans. Aging (Albany NY) 8:1416-31

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