Calorie restriction, SIRT1 and metabolism: understanding longevity

Calorie restriction (CR) is a dietary regimen, which has been shown to extend lifespan in a multitude of organisms. In addition, CR has been shown to reduce the incidence of age-related disorders (such as diabetes, cancer and cardiovascular disorders).CR induces metabolic changes, improves insulin sensitivity and alters neuroendocrine functions in animals.CR is a highly regulated process, which requires regulatory proteins that can sense food scarcity and mount an appropriate physiological response. The NAD-dependent deacetylase SIRT1 might link the energetics of cells to their lifespan.CR has been shown to produce changes in the levels of hormones that are produced in the fat tissue (such as adiponectin, leptin, TNFα and resistin) that could mediate the beneficial effects of this regimen.SIRT1 renders cells stress resistant by inhibiting the pro-apoptotic transcription factors p53 and forkhead. And, in white adipose tissue, SIRT1 has been shown to mobilize fat by repressing peroxisome proliferator-activated receptor (PPAR)γ.CR has beneficial effects on glucose metabolism, and CR mice have lower glucose and insulin levels.CR can protect against neurodegeneration in animal models of Huntington's disease, Alzheimer's disease, Parkinson's disease and stroke.The levels of uncoupling proteins increase under CR and this might ameliorate the generation of oxidative damage by reducing reactive oxygen species and, thereby, slowing ageing.