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Calorie restriction (CR) extends life span and retards age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast. The mechanism or mechanisms through which this occurs are unclear. CR reduces metabolic rate and oxidative stress, improves insulin sensitivity, and alters neuroendocrine and sympathetic nervous system function in animals. Whether prolonged CR increases life span (or improves biomarkers of aging) in humans is unknown. In experiments of nature, humans have been subjected to periods of nonvolitional partial starvation. However, the diets in almost all of these cases have been of poor quality. The absence of adequate information on the effects of good-quality, calorie-restricted diets in nonobese humans reflects the difficulties involved in conducting long-term studies in an environment so conducive to overfeeding. Such studies in free-living persons also …