An interesting paper on calorie restriction biochemistry via PubMed: "Both life-long caloric restriction (CR) and the suppression of insulin-like growth factor-1 (IGF-1) signaling reliably extend the mammalian lifespan. The neuroendocrine system, regulated by the hypothalamus, remains the most convincing site of action for both these modes of life extension. Yet, determining whether CR actions are mediated by the modulation of neuroendocrine IGF-1 signaling remains unclear. ... while CR induces greater loss in the total number of cells in the [supraoptic nucleus (SON)] with age, it reduces the degree of age-dependent loss seen in [IGF-1 receptor (IGF-1R)] expressing cells. As a result, when compared to [old ad libitum fed] mice, the SON of [old calorie restricted] mice displays a greater proportion of IGF-1R cells and thus possibly enhanced IGF-1 sensitivity with aging." It's all pretty interesting, but remember that tinkering with metabolism is a dead end road - the gains will be minor and expensive in comparison to other ways forward.