John O. Holloszy, M.D.

DEPARTMENT OF Internal Medicine
Keywords: aging, caloric restriction, exercise, energy balance, overweight

Primary aging is the progressive deterioration in structure and function with advancing age that occurs independently of disease and lifestyle/environmental factors. Slowing of primary aging results in an increase in maximal life span. Caloric restriction (CR) slows primary aging in various short-lived organisms, such as guppies, flies, mice and rats. It is not known if CR slows primary aging in humans. Secondary aging is due to disease processes and harmful lifestyle/environmental factors. Protection against secondary aging results in rectangularization of the mortality curve without an extension of maximal life span. Available evidence suggests that CR protects against some aspects of secondary aging in primates. In contrast to CR, an exercise-induced caloric deficit does not slow primary aging in rats, suggesting that the effect of CR on primary aging is mediated by decreased intake and metabolism of food rather than by decreased energy availability. In this context, the specific aims of phase 1 of this study are: 1) to determine the feasibility of achieving prolonged 20% restriction of energy intake or prolonged 20% increase of energy expenditure by exercise, in overweight 50-60 year old women and men and refine the techniques needed to achieve adherence to the CR and exercise protocols. The efficaciousness of two approaches will be evaluated for CR (meal plans vs. meal replacement) and for exercise (supervised vs. independent exercise programs); and 2) to evaluate and compare the effects of 12 months of the CR and exercise interventions on a number of potential markers of aging, on body composition and on risk factors for CAD and type 2 diabetes. In phase 1, volunteers will be randomized to one of five groups: two CR groups, two exercise groups and one control group. There will be 16 participants per intervention group (i.e., 32 CR, 32 exercise) and 20 in the control, no intervention group. We anticipate a drop-out rate of about 25% based on previous experience. Our goal is to have at least 12 women and 12 men complete 1 year of CR, and 12 women and 12 men complete one year of exercise in phase 1. The information obtained from the first two years (phase 1) of this research, will be used in the planning and design of phase 2. It should be possible to more accurately estimate the number of participants per group in phase 2 based on our experience in phase 1. In phase 2, there will be three groups of healthy, overweight men and women aged 50-60 years: CR, exercise and control. The CR and exercise protocols will be designed on the basis of our experience and that of the other investigators in phase 1. In phase 2, the duration of the CR and exercise interventions will be two years.