Here are some of my favorite fun facts in this area :

Caloric restriction has been known for decades to cause lifespan increase in lower organisms, but we've never really known why. This pathway however shed lots of light when it was elucidated. Since DAF-2 is homologous with the insulin/IGF receptor, it provides a mechanistic link between nutrient status and recycling/repair pathways in the cell that are thought to cleanup intracellular junk.

But even more evidence has come forward! Some stunning work by the Panda lab has demonstrated that intermittent fasting can also boost lifespan, and this benefit can be completely separated from calorie count! His lab has shown that restricting mealtimes itself is sufficient to promote longevity even if the calorie intake is the same as with control animals. The time restricted mice are also lean, which sheds some interesting perspectives on obesity research :)

The last interesting evidence has come forward with methionine restriction studies. In these experiments, mice are fed a diet in which the amino acid methionine is restricted, but all else is equal. These mice benefit from dramatic improvements in longevity and are also incredibly lean towards the end of their life. Whats going on?

Methionine is the amino acid that starts every single protein, so without it, the body cannot synthesize new proteins unless it is scavenged from other existing proteins. This potentially turns up the same recycling pathways that were elucidated in the DAF-2/DAF-16 pathway! But this remains to be determined.

In short, we always thought that calories were all that mattered in metabolic syndrome and aging, but maybe the true answers are much more specific!