Caloric restriction and aging revisited: The need for a geometric analysis of the nutritional bases of aging

One of the most important findings in the field of the biology of aging has been the demonstration that modest dietary restriction extends life span in a wide range of taxonomically disparate organism. There is currently a debate as to whether longevity is prolonged because of caloric restriction or due to more specific nutrient effects. Recent advances in nutritional research, notably the development of state-space geometric models, the Geometric Framework (GF), offer new opportunities to disentangle the effects of calories and nutrients. We begin by introducing these models, then set out the four questions that must be addressed to establish the relationship between nutrition and aging and indicate how the GF might help in answering these. We next provide an exemplar experimental protocol and consider some practical challenges to implementing the GF. Our conclusion is that Drosophila provides the most suitable system for an initial study.