Research press release


Nature Metabolism

A nutritional memory effect counteracts the benefits of dietary restriction in old mice



今回、Linda Partridgeたちは、24月齢の雌のマウス800匹で食餌制限の効果を調べた。マウスの一部は、制限しない自由食から食餌制限へと切り替え、一部はその逆を行った。食餌制限から制限なしに切り替えたマウスは、すぐに不健康になり、食餌制限をそのまま続けたマウスよりも早く死んだ。しかし、食餌制限なしから食餌制限に切り替えたマウスは、そのまま食餌制限なしを続けたマウスに比べて健康ではあったものの、長生きはしなかった。著者たちは、一生のほとんどの期間、制限されずに食物を摂取できていたマウスでは、食餌制限に対する脂肪組織での分子レベルの応答が違っていることを見いたした。著者たちは、脂肪組織に「栄養状態の記憶」が刻まれていて、これが食餌制限の健康や生存に及ぼす効能を抑制するのだろうと述べている。


Switching to a dietary-restricted (DR) diet later in life does not make mice live longer, a study published in Nature Metabolism reports. The findings suggest that the late adoption of a healthful diet cannot undo the damage caused by a previously unrestricted diet. Whether these findings translate to humans remains to be seen.

Lifelong dietary restriction (20 - 40% reduction of normal calorie intake) has well-documented health benefits and is known to extend the lifespan of many animals. However, whether dietary restriction still works when initiated relatively late in life is unclear.

Linda Partridge and colleagues investigated the effects of dietary restriction in 800, 24-month-old female mice. Some mice were switched from an unrestricted, ad libitum diet to a DR diet or vice versa. Mice switched from a DR to an unrestricted diet quickly became unhealthy and died earlier than those that remained on a DR diet. However, even though they were healthier, the mice switched from an unrestricted to a DR diet did not live longer than mice that remained on an unrestricted diet. The authors found that the molecular response to a DR diet was different in the fat tissues of the mice previously given unrestricted access to food for most of their life. The authors propose a ‘nutritional memory effect’ in fat tissue that suppresses the beneficial effects of dietary restriction on health and survival.

The study provides a detailed investigation into the potential benefits of late-onset DR in mice. However, the authors highlight that whether the molecular mechanisms underlying the proposed nutritional memory effect also apply to humans remains to be established.

doi: 10.1038/s42255-019-0121-0

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