Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes

The current societal environment is marked by overabundant accessibility of food coupled with a strong trend of reduced physical activity, both leading to the development of a constellation of disorders, including central obesity, insulin resistance, dyslipidemia, and hypertension (metabolic syndrome). Prolonged calorie restriction (CR) has been shown to extend both the median and maximal lifespan in a variety of lower species such as yeast, 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, inflammation, and functional changes in both the neuroendocrine and sympathetic nervous systems. Here we review some of the major physiological, psychological, and behavioral changes after 6 months of CR in overweight otherwise healthy volunteers. Special emphasis is given to the first completed clinical studies that have investigated the effects of controlled, high-quality energy-restricted diets on both biomarkers of longevity and on the development of chronic diseases related to age in humans. With the incremental expansion of research endeavors in the area of energy or caloric restriction, data on the effects of CR in animal models and human subjects are becoming more accessible.