Now that calorie restriction is becoming a much more popular - and well funded - field of research, we are starting to see a range of basic, thoughtful tests as well as forward-looking work on genetics, biochemical mechanisms and calorie restriction mimetic drugs. Betterhumans covers some of the latest results in flies:
Cutting fat and protein extends fly lifespan without cutting calories, providing further insight into the effects of diet on longevity.
Researchers varied the nutrients in the fly's standard lab diet of yeast and sugar. Both yeast (which contributes protein and fat) and sugar (carbohydrates) have the same calories per gram, allowing the researchers to adjust nutrient composition without affecting the calorie count. They found that reducing both nutrients increased the flies' life span, but cutting out the yeast had nearly as great an effect. Flies on a calorie-restricted diet lived 82% longer than controls, flies on the yeast-restricted diet had a 65% gain and flies on a sugar-restricted diet had just about a 9% gain.
The original paper can be read in full at PLoS Biology. The obvious next step is to try something similar in mammals (such as mice) and see what happens; I will be interested to see the biochemical explanations for these results, bearing in mind the information that researchers have uncovered to date.