June 24, 2024

New Study Unveils Mechanism Behind Keto Diet's Brain Benefits in Aging Male Mice

Recent research has revealed a potential mechanism underlying the cognitive improvements observed in older male mice on c diets, raising intriguing questions about the role of diet in aging and brain health. The study, published in *Cell Reports Medicine*, indicates that cycling male mice between a control diet and a ketogenic diet enhances synaptic signaling in the brain.

Background and Previous Findings
Dr. John Newman, one of the study's authors, previously demonstrated that a cyclic ketogenic diet reduced midlife mortality and prevented age-related memory decline in male mice. Building on these findings, Christian González-Billault, a professor at Universidad de Chile and director of the Geroscience Center for Brain Health and Metabolism (GERO), collaborated with Newman to investigate the molecular mechanisms driving these benefits.
Study Design and Results
The researchers examined 19 male mice aged 20-23 months, either maintained on a control diet or cycled with a ketogenic diet every other week. Over 12 weeks, the mice's metabolic parameters were measured, followed by 5 weeks of behavioral testing. The results showed that the ketogenic diet was linked to lower blood sugar levels, improved memory, and enhanced motor ability in the older mice. Notably, there was increased plasticity in the hippocampus, attributed to a molecule called a ketone body, which activates a signaling pathway between synapses.

Implications and Future Research
The findings suggest that ketogenic diets may help maintain resilience in aging mice by improving physiological functions. This concept is critical in aging research, differentiating between lifespan and healthspan — the latter being the period free from chronic diseases. González-Billault emphasized that while the benefits were significant in older mice, similar effects were not observed in younger mice, possibly due to their existing resilience mechanisms.

Keto Diet in Human Studie
Small human studies suggest potential cognitive benefits of the keto diet, particularly for older adults with dementia, potentially mirroring mechanisms seen in mice. However, adherence to the ketogenic diet can be challenging, and it may reduce the intake of essential nutrients. Thus, experts often recommend the Mediterranean or DASH diets for healthy aging due to their extensive human research support.

Gender and Further Research
The study's findings are currently limited to male mice. González-Billault acknowledged this limitation and highlighted the need to investigate the diet's effects on female mice, considering gender-specific metabolic differences. Future research will explore whether the observed brain benefits are solely brain-dependent or involve systemic effects and other organs' functions.