Research press release


Nature Metabolism

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

マウスのカロリー制限食がもたらす寿命の延長や代謝面の有益効果は、単に摂取カロリーが減少することだけでなく、1日の絶食時間が長くなることが原因である可能性がある。このことを報告する論文が、Nature Metabolism に掲載される。ただし、この知見を、例えば別の系統のマウスや性別の異なるマウスにも一般化できるかを明らかにするには、さらに研究が必要だろう。


今回、Dudley Lamming、Heidi Pakたちは、雄マウスを3つのグループに分け、いずれにも、1日の摂取カロリーを30%減らした食餌を、異なったやり方で16週にわたって与えた。1つ目のグループは食餌を制約なしに摂取できるようにし、2つ目のグループは、同じ量の食餌を12時間のうちに3回摂取した。3つ目のグループは、食餌を大急ぎで食べるよう訓練したため、1日の残りの時間は「絶食」することになった。さらに、げっ歯類の通常の食餌をカロリー制限せずに与えたマウスを対照群とした。実験の結果、インスリン感受性や栄養素の代謝の変化をもたらすには、絶食が重要であることが分かった。実際、絶食だけで(カロリー制限をしないでも)、カロリー制限に関係する代謝や転写へのある種の効果を再現できた。ある特定の系統の雄マウスで、カロリー制限によってグルコース代謝やフレイルの改善、寿命の延長を引き起こすためには、絶食が必要であった。


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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