This study is one of three CALERIE trials that test the hypothesis that a reduced calorie, nutritionally sound diet improves biomarkers of aging and prevents some age-related chronic diseases such as cancer, diabetes, and cardiovascular disease. The three sites that are participating in the CALERIE trial represent a diversity of subject populations and interventional strategies.

This study tests whether chronic caloric restriction improves risk factors of longevity in humans as it is known to do in animals, by measuring a variety of factors dealing with metabolism and oxidative stress, through physical evaluations and laboratory tests.

Participants will receive dietary counseling and free medical evaluations. In addition, each volunteer will be asked to do one of the following:

1. Follow a reduced calorie diet
2. Follow a reduced calorie diet using a liquid diet
3. Increase physical activity while on a reduced calorie diet
4. Follow a standard diet.

Three separate five-day inpatient stays are required.

• Aging
• Cardiovascular Disease
• Diabetes Mellitus

• Behavioral: Caloric Restriction (CR)
• Behavioral: Exercise

• Heilbronn LK, de Jonge L, Frisard MI, DeLany JP, Larson-Meyer DE, Rood J, Nguyen T, Martin CK, Volaufova J, Most MM, Greenway FL, Smith SR, Deutsch WA, Williamson DA, Ravussin E; Pennington CALERIE Team. Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA. 2006 Apr 5;295(13):1539-48.
• Heilbronn LK, Ravussin E. Calorie restriction and aging: review of the literature and implications for studies in humans. Am J Clin Nutr. 2003 Sep;78(3):361-9. Review.
• Jenkins RR, Goldfarb A. Introduction: oxidant stress, aging, and exercise. Med Sci Sports Exerc. 1993 Feb;25(2):210-2. Review. Erratum in: Med Sci Sports Exerc 1993 May;25(5):653.
• Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science. 1996 Jul 5;273(5271):59-63. Review.
• Ryan AS. Insulin resistance with aging: effects of diet and exercise. Sports Med. 2000 Nov;30(5):327-46. Review.
• Masoro EJ. Food restriction in rodents: an evaluation of its role in the study of aging. J Gerontol. 1988 May;43(3):B59-64. Review. No abstract available.
• Anton SD, Han H, York E, Martin CK, Ravussin E, Williamson DA. Effect of calorie restriction on subjective ratings of appetite. J Hum Nutr Diet. 2009 Apr;22(2):141-7.
• Redman LM, Heilbronn LK, Martin CK, de Jonge L, Williamson DA, Delany JP, Ravussin E; Pennington CALERIE Team. Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss. PLoS ONE. 2009;4(2):e4377. Epub 2009 Feb 9.
• Redman LM, Rood J, Anton SD, Champagne C, Smith SR, Ravussin E; Pennington Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) Research Team. Calorie restriction and bone health in young, overweight individuals. Arch Intern Med. 2008 Sep 22;168(17):1859-66.
• Redman LM, Heilbronn LK, Martin CK, Alfonso A, Smith SR, Ravussin E; Pennington CALERIE Team. Effect of calorie restriction with or without exercise on body composition and fat distribution. J Clin Endocrinol Metab. 2007 Mar;92(3):865-72. Epub 2007 Jan 2.

Inclusion Criteria:

• Resident of greater Baton Rouge area for 1 year or longer
• Men between ages 25-50
• Women between ages 25-45
• Body Mass Index (BMI) between 25-30 (never having had BMI greater than 32)
• Healthy, non-smokers with no history of cardiovascular disease, high blood pressure, diabetes, eating disorder, or major psychiatric disorder

Exclusion Criteria:

• Pregnant or breastfeeding
• Personal history of cardiovascular disease or elevated high blood pressure (higher than 160/90 mmHg)
• Abnormal electrocardiogram (EKG)
• Personal history of diabetes
• Personal history of major psychiatric disorders
• Personal history of eating disorder
• Smoking
• Exercising regularly (more than twice a week)
• Individuals with alcoholism or other substance abuse
• Post obese (never have had a BMI greater than 32)
• Regular use of medications, except oral contraceptives
• Individuals who were ever injured by a metallic foreign body which was not removed
• Individuals who wear braces on their teeth, have non-removable false teeth, or non-removable bridgework
• Individuals in occupations requiring full alertness and motor skills (airline pilots, etc.) where even a small chance of postural dizziness would be unacceptable.