Calorie restriction (CR) without malnutrition slows aging and increase average and maximal lifespan in model organisms and rodents. In human and non-human primates, CR has beneficial effects on human longevity and reduces the incidence of age-related diseases such as obesity, diabetes mellitus hypertension, cardiovascular disease and cancer. CR exerts its anti-aging effects through different mechanisms including small noncoding RNA molecules (sncRNAs), the composition of diet and IGF-1 signaling. The aim of this review was to discuss recent developments to understand the consequences and mechanisms of CR on longevity.