Ketogenic diets recapitulate certain metabolic aspects of dietary restriction such as reliance on fatty acid metabolism and production of ketone bodies. We investigated whether an isoprotein ketogenic diet (KD) might, like dietary restriction, affect longevity and healthspan in C57BL/6 male mice. We find that Cyclic KD, KD alternated weekly with the Control diet to prevent obesity, reduces midlife mortality but does not affect maximum lifespan. A non-ketogenic high-fat diet (HF) fed similarly may have an intermediate effect on mortality. Cyclic KD improves memory performance in old age, while modestly improving composite healthspan measures. Gene expression analysis identifies downregulation of insulin, protein synthesis, and fatty acid synthesis pathways as mechanisms common to KD and HF. However, upregulation of PPARα target genes is unique to KD, consistent across tissues, and preserved in old age. In all, we show that a non-obesogenic ketogenic diet improves survival, memory, and healthspan in aging mice.

中文翻译：

---

生酮饮食可降低中年死亡率，并改善衰老小鼠的记忆力。

生酮饮食概括了饮食限制的某些代谢方面，例如对脂肪酸代谢的依赖和酮体的产生。我们调查了同蛋白生酮饮食（KD）是否可能像饮食限制一样影响C57BL / 6雄性小鼠的寿命和健康寿命。我们发现，周期性KD，KD每周与对照组饮食交替进行，以防止肥胖，降低中年死亡率，但不影响最大寿命。同样喂养的非生酮高脂饮食（HF）可能对死亡率有中等影响。循环KD可以改善老年时的记忆性能，同时适度改善复合健康跨度措施。基因表达分析确定胰岛素下调，蛋白质合成和脂肪酸合成途径是KD和HF常见的机制。然而，PPARα靶基因的上调是KD独有的，在组织中一致，并在老年时保留。总而言之，我们表明，非致肥胖的生酮饮食可改善衰老小鼠的存活，记忆和健康状况。