The effect of caloric restriction on physiological, psychological and behavioral outcomes in humans: Results from CALERIE

Abstract

The focus of this chapter is on current research involving long-term calorie restriction (CR) in humans and the resulting physiological and behavioral changes. Special emphasis is given to the first completed clinical studies which have investigated the effects of controlled, high-quality energy-restricted diets on both biomarkers of longevity and on risk factors for the development of chronic diseases of aging. Prolonged CR has been shown to extend both the median and maximal lifespan in a variety of lower animal species such as worms, fish, rats, and mice. Mechanisms of this CR-mediated lifespan extension are not fully elucidated, but possibly involve significant alterations in energy metabolism, oxidative damage, insulin sensitivity, and functional changes in both the neuroendocrine and sympathetic nervous systems. In this brief report, we review some of the major physiological, psychological and behavioral changes after 6 months of CR in overweight otherwise healthy volunteers. Ongoing studies of prolonged CR in humans are now making it possible to analyze changes in biomarkers of longevity to unravel some of the mechanisms of its anti-aging phenomenon. With the incremental expansion of research endeavors in the area of energy restriction, data on the effects of CR in animal models and human subjects are becoming more accessible. Detailed analyses from controlled human trials involving long-term CR will allow investigators to link observed alterations from body composition down to changes in molecular pathways and gene expression, with their possible effects on the biomarkers of aging.