IN the seminal 1935 publication, McCay and colleagues (1) reported that calorie restriction increased lifespan of white rats. Their primary hypothesis was that "a slow rate of growth results in an increased lifespan." In order to slow the rate of growth, the food provided to the rats was down-titrated to maintain slow growth and a low body weight, whereas the control rats had unlimited access to food. This work has been cited over 1,300 times and has led to the dogma that calorie restriction is the most robust intervention to delay ageing. The conclusion has been replicated across taxa (2), and there are health benefits-if not longevity extension-seen in humans (3) and nonhuman primates (4). The relationship between calorie intake and ageing has led to important insights into the molecular switches (target of rapamycin, sirtuins, insulin/IGF-1/growth hormone, 5' adenosine monophosphate-activated protein kinase) that interface between dietary intake and those cellular processes (mitochondrial function, autophagy, DNA repair, oxidative stress) that influence the rate of ageing (5).
展开▼
