Starvation

Low calorie diet

Biology

Weight loss

Caloric intake

Endocrinology

Caloric theory

Restricted diet

Intermittent fasting

Calorie restriction

Physiology

Genetics

Ageing

Calorie

Longevity

Body weight

Internal medicine

Medicine

Obesity

Nature Metabolism

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. Pak et al. show that prolonged fasting is required for the effects of calorie restriction on insulin sensitivity, fuel utilization and ageing in mice.

Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice