Calorie restriction (CR) promotes healthy ageing in diverse species. Recently, it has been shown that fasting for a portion of each day has metabolic benefits and promotes lifespan. These findings complicate the interpretation of rodent CR studies, in which animals typically eat only once per day and rapidly consume their food, which collaterally imposes fasting. Here we show that a prolonged fast is necessary for key metabolic, molecular and geroprotective effects of a CR diet. Using a series of feeding regimens, we dissect the effects of calories and fasting, and proceed to demonstrate that fasting alone recapitulates many of the physiological and molecular effects of CR. Our results shed new light on how both when and how much we eat regulate metabolic health and longevity, and demonstrate that daily prolonged fasting, and not solely reduced caloric intake, is likely responsible for the metabolic and geroprotective benefits of a CR diet.

热量限制（CR）可促进不同物种的健康衰老。最近，研究表明，每天禁食一段时间有利于新陈代谢并延长寿命。这些发现使啮齿类动物 CR 研究的解释变得复杂，在这些研究中，动物通常每天只吃一次，并迅速消耗食物，这间接导致了禁食。在这里，我们表明，长时间禁食对于 CR 饮食的关键代谢、分子和衰老保护作用是必要的。通过一系列的喂养方案，我们剖析了卡路里和禁食的影响，并继续证明仅禁食就可以概括 CR 的许多生理和分子效应。我们的研究结果为我们饮食的时间和摄入量如何调节代谢健康和寿命提供了新的线索，并证明每日长期禁食，而不仅仅是减少热量摄入，可能是 CR 饮食的代谢和老年保护益处的原因。