Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice

Publication date: 5 September 2017
Source:Cell Metabolism, Volume 26, Issue 3
Author(s): John C. Newman, Anthony J. Covarrubias, Minghao Zhao, Xinxing Yu, Philip Gut, Che-Ping Ng, Yu Huang, Saptarsi Haldar, Eric Verdin
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.

Graphical abstract

Teaser

Ketogenic diet is similar in many physiological respects to dietary restriction. Newman et al. show that a cyclic ketogenic diet reduces mortality and improves memory as mice age. Ketogenic diet gene expression pattern is similar to high-fat diet, except for activation of PPARα targets. See related paper by Roberts et al.


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