PLX058279

GSE101657: Gene expression changes in ketogenic and high-fat diets

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

The ketone body -hydroxybutyrate (BHB) is produced during dietary restriction, fasting, and exercise. A ketogenic diet (KD) results in long-term production of BHB outside of these contexts. We sought to determine a protein-matched, non-obese ketogenic diet (KD) would affect the longevity and healthspan of C57BL/6 male mice. We find that feeding KD every-other-week to prevent obesity (cyclic KD) reduces mid-life mortality but does not affect maximum lifespan. Similar feeding of a non-ketogenic high-fat/low-carbohydrate (HF) diet may have an intermediate effect on mortality. Cyclic KD improves memory performance in old age, while modestly improving composite measures of healthspan. RNAseq gene expression analysis identifies down-regulation of insulin, TOR, and fatty acid synthesis pathways as possible longevity mechanisms common to KD and HF. However, up-regulation of fasting-related PPAR target genes is unique to KD, consistent across tissues, and preserved in old age, suggesting a mechanism for an incremental benefit from KD. In all, we show that a non-obese ketogenic diet improves survival, memory, and healthspan into old age. These gene expression studies were carried out on 12 month-old male C56BL/6 mice from the NIA Aged Rodent Colony, habituated to AIN-93M control diet and then either maintained on this diet or switched for one week to a 75% kcal fat non-ketogenic high-fat diet or a 90% kcal fat ketogenic diet (all diets with 10% kcal from carbohydrates). Tissues were harvested in the middle of the nighttime feeding period (MN-3am). SOURCE: John,C,Newman (newman@ucsf.edu) - UCSF