Long-term ketogenic diet increases expression of SOX2-dependent oligodendrocyte- and myelination-associated genes in the aged mouse brain.

Abstract

Aging is associated with multiple neurodegenerative conditions that severely limit quality of life and shorten lifespan. Studies in rodents indicate that in addition to extending lifespan, the ketogenic diet improves cognitive function in aged animals, thus improving healthspan. To broadly investigate what mechanisms might be activated in the brain in response to ketogenic diet, we conducted transcriptome wide analysis on whole brain samples from 13-month-old mice, 26-month-old mice, and 26-month-old mice fed a ketogenic diet. We observed clear activation of inflammation and complement system pathways in the 26-month-old mice relative to the younger animals. Interestingly, ketogenic diet caused a modest but significant increase in the expression of SOX2-dependent oligodendrocyte/myelination markers.