A nutritional memory effect counteracts benefits of dietary restriction in old mice.,Nature Metabolism

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A nutritional memory effect counteracts benefits of dietary restriction in old mice.
Nature Metabolism ( IF 18.9 ) Pub Date : 2019-10-21 , DOI: 10.1038/s42255-019-0121-0
Oliver Hahn _{1,

2,

3} , Lisa F Drews ₁ , An Nguyen ₄ , Takashi Tatsuta ₁ , Lisonia Gkioni ₁ , Oliver Hendrich ₁ , Qifeng Zhang ₄ , Thomas Langer ₁ , Scott Pletcher ₅ , Michael J O Wakelam ₄ , Andreas Beyer _{2,

6} , Sebastian Grönke ₁ , Linda Partridge _{1,

7}

Affiliation

Dietary restriction (DR) during adulthood can greatly extend lifespan and improve metabolic health in diverse species. However, whether DR in mammals is still effective when applied for the first time at old age remains elusive. Here, we report results of a late-life DR switch experiment employing 800 mice, in which 24 months old female mice were switched from ad libitum (AL) to DR or vice versa. Strikingly, the switch from DR-to-AL acutely increases mortality, whereas the switch from AL-to-DR causes only a weak and gradual increase in survival, suggesting a memory of earlier nutrition. RNA-seq profiling in liver, brown (BAT) and white adipose tissue (WAT) demonstrate a largely refractory transcriptional and metabolic response to DR after AL feeding in fat tissue, particularly in WAT, and a proinflammatory signature in aged preadipocytes, which is prevented by chronic DR feeding. Our results provide evidence for a nutritional memory as a limiting factor for DR-induced longevity and metabolic remodeling of WAT in mammals.

中文翻译：

营养记忆效应抵消了老年小鼠饮食限制的好处。

成年期的饮食限制 (DR) 可以极大地延长寿命并改善不同物种的代谢健康。然而，在哺乳动物中首次应用 DR 是否仍然有效仍是未知数。在这里，我们报告了一项使用 800 只小鼠的晚年 DR 切换实验的结果，其中 24 个月大的雌性小鼠从随意 (AL) 切换到 DR，反之亦然。引人注目的是，从 DR 到 AL 的转变会急剧增加死亡率，而从 AL 到 DR 的转变只会导致生存率微弱且逐渐增加，这表明对早期营养的记忆。肝脏、棕色 (BAT) 和白色脂肪组织 (WAT) 中的 RNA-seq 分析表明，在脂肪组织中，特别是在 WAT 中进行 AL 喂养后，对 DR 的转录和代谢反应在很大程度上是难治的，并且在老年前脂肪细胞中具有促炎特征，这可以通过慢性 DR 喂养来预防。我们的研究结果为营养记忆作为 DR 诱导的哺乳动物寿命和 WAT 代谢重塑的限制因素提供了证据。

更新日期：2019-10-22

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