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Physiology: Fasting may mediate the beneficial effects of calorie restriction in mice

Nature Metabolism

October 19, 2021

Daily prolonged fasting — not solely reducing calorie intake — is likely to be responsible for the lifespan-promoting and beneficial metabolic effects associated with a calorie-restricted diet in mice, according to a study published in Nature Metabolism. Further research, however, will be required to decipher the generalisability of these findings, for example in different strains and sexes of mice.

Calorie restriction is known to promote healthy ageing in many species. Recently, evidence for the lifespan-promoting and metabolic benefits of fasting in mice has emerged. However, the exact physiological and molecular mechanisms which underlie the effects of controlling when food is eaten have so far remained elusive.

Dudley Lamming, Heidi Pak and colleagues placed 3 groups of male mice on different diets, all of which reduced their daily calorie intake by 30% for 16 weeks. Every day, one group would have unlimited access to their food, another group would receive food in 3 equal meals spaced over a 12-hour period, and the other group was trained to rapidly consume their food, subsequently ‘fasting’ for the remainder of the day. Mice receiving a normal rodent diet without calorie restriction acted as controls. The authors found that fasting was important for mediating changes in insulin sensitivity and nutrient metabolism. Indeed, fasting alone — without restricting calorie intake — was able to replicate certain metabolic and transcriptional effects associated with calorie-restriction. In a specific strain of male mice, fasting was required for calorie-restriction-induced improvements in glucose metabolism, frailty and lifespan.

The authors conclude that these results could provide preliminary insights into how the regulation of metabolic health and longevity might not just be about how much is eaten but also when. They go on to state that caution is warranted in applying these results to humans, which will represent an important area of future research.

doi: 10.1038/s42255-021-00466-9

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