[PDF][PDF] Ketogenic diet reduces midlife mortality and improves memory in aging mice

JC Newman, AJ Covarrubias, M Zhao, X Yu, P Gut… - Cell metabolism, 2017 - cell.com
JC Newman, AJ Covarrubias, M Zhao, X Yu, P Gut, CP Ng, Y Huang, S Haldar, E Verdin
Cell metabolism, 2017cell.com
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 …
Summary
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.
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