Here is a commentary on what is known of the effects of calorie restriction in humans, and the prospects for determining whether or not it actually extends life in our species, from one of the foremost researchers in the field:
Calorie Restriction (CR) without malnutrition is the most powerful nutritional intervention that has consistently been shown to increase maximal and average lifespan in a variety of organisms, including yeasts, worms, flies, spiders, rotifers, fish and rodents. Far from merely stretching the life of an old, ill and weak animal, CR extends longevity by preventing chronic diseases, and by preserving metabolic and biological functions at more youthful-like state. In rodents, the CR-mediated preventive effects are widespread with major reductions in the occurrence and/or progression of cancer, nephropathy, cardiomyopathy, obesity, type 2 diabetes, neuro-degenerative disease, and several autoimmune diseases.
Whether or not CR without malnutrition will extend lifespan in humans is not known yet, but accumulating data indicate that moderate CR with adequate nutrition has a powerful protective effect against the development of obesity, type 2 diabetes, inflammation, hypertension and cardiovascular disease, which are major causes of morbidity, disability and mortality. In humans calorie restriction without malnutrition also results in a consistent reduction in circulating levels of growth factors, anabolic hormones, adipokines and inflammatory cytokines, which are associated with an increased risk of some of the most common types of cancer.
Moreover, CR in these individuals resulted in an amelioration of two well-accepted markers of cardiovascular aging, i.e. left ventricular diastolic function and heart rate variability. These data indicate that CR exerts direct systemic effects that counter the expected age-associated changes in myocardial stiffness and autonomic function so that LV diastolic function and heart rate variability indexes in CR individuals are similar to those of individuals 20 years younger on a typical Western diet. Consistently, we recently found that CR without malnutrition results in dramatic changes of the human skeletal muscle transcriptional profile that resemble those of younger individuals.
More studies are needed to understand how macro- and micro-nutrients, endurance exercise, and other environmental and psychological factors interact with CR in modulating metabolic and molecular pathways that regulate health and longevity. Randomized, CR-controlled, long-term survival studies in humans will never be performed because of obvious problems with long-term compliance and costs of such a long study. Nonetheless, we hope that by following the health status of individuals practicing long-term CR without malnutrition, in particular of those who are now in their 70s and 80s, we could gain soon some information about the effects of CR on successful aging and healthy longevity in humans as well. Because we have detailed information about their close relatives' disease and survival histories, if we observe that as the [CR practitioners] age, they don't develop any of the metabolic abnormalities and/or chronic diseases typical of their parents/siblings, and live substantially longer than their relatives, this will be the best available proof that CR works in humans.