Reducing morbidity and delaying mortality are recognized as major goals of aging research, and are addressed by this proposal to conduct a 2-year human caloric restriction (CR) intervention. A 1-year pilot study will be conducted in 32 overweight men and women to develop an effective CR regimen when fed at 70% of energy requirements determined at baseline. As part of this pilot we will refine all aspects of a CR intervention, including exercise and behavioral counseling, and will obtain necessary information on outcome variability with which to perform power calculations for the main study. Subjects will be randomized to two dietary regimens with different levels of dietary fat and glycemic index (GI) (20% fat and moderate GI vs. 35% fat and low GI) and dietary compliance and key outcome measurements will be determined at 5 periods throughout the year. Dietary factors such as dietary variety, liquid sources of energy, and dietary fiber will then be taken into account in the design of the interventions. Following identification of an effective CR regimen, a randomized 2- year intervention will be conducted in 117 overweight men and women fed 70%, 80% or 100% of energy requirements determined at baseline. The hypothesis will be tested that, compared to control subjects fed 100% of baseline energy requirements. The parameters to be evaluated will include immune function, oxidative stress, fasting insulin, hemoglobin Alc, and cardiopulmonary function. W further hypothesize that, compared control subjects, individuals randomized to 70% or 80% of baseline energy requirements will not experience adverse change sin thyroid and reproductive hormones, bone mineral density, disease incidence, mood or cognitive function. Dose-response relationships between the extent of CR and changes in outcome variables are anticipated. As part of the study, changes in total energy expenditure and resting metabolic rate, body composition and body temperature will be quantified to document the effects of CR on energy metabolism. We anticipate that the results of this study will have a major impact on our understanding of the relevance of CR to human health. In addition, this study will contribute to the development of new avenues for long- term treatment of overweight and obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AG020480-07
Application #
7457983
Study Section
Special Emphasis Panel (ZRG1-GRM (04))
Program Officer
Romashkan, Sergei
Project Start
2002-05-15
Project End
2009-08-31
Budget Start
2008-05-01
Budget End
2009-08-31
Support Year
7
Fiscal Year
2008
Total Cost
$319,082
Indirect Cost
Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111
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
Most, Jasper; Tosti, Valeria; Redman, Leanne M et al. (2017) Calorie restriction in humans: An update. Ageing Res Rev 39:36-45
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
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
Romashkan, Sergei V; Das, Sai Krupa; Villareal, Dennis T et al. (2016) Safety of two-year caloric restriction in non-obese healthy individuals. Oncotarget 7:19124-33
Martin, Corby K; Bhapkar, Manju; Pittas, Anastassios G et al. (2016) Effect of Calorie Restriction on Mood, Quality of Life, Sleep, and Sexual Function in Healthy Nonobese Adults: The CALERIE 2 Randomized Clinical Trial. JAMA Intern Med 176:743-52
Fontana, Luigi; Villareal, Dennis T; Das, Sai K et al. (2016) Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: a randomized clinical trial. Aging Cell 15:22-7
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
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
Sanghvi, Arjun; Redman, Leanne M; Martin, Corby K et al. (2015) Validation of an inexpensive and accurate mathematical method to measure long-term changes in free-living energy intake. Am J Clin Nutr 102:353-8

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