How keto diets may help boost memory, brain health later in life

• Research has already shown that ketogenic diets may improve brain performance in older male mice.
• Now, the authors of a new study in mice have identified a particular mechanism that might underpin this phenomenon.
• The research raises questions about the role of diet in aging and brain health.

Researchers have discovered a potential mechanism underpinning the improvements seen in aging male mice on ketogenic diets — “keto diets,” for short.

They have proposed that cycling male mice between a control diet and a ketogenic diet results in an improvement in the signalling that occurs between synapses in the brain.

Previously, John Newman, MD, PhD, one of the authors of the paper, had published a proof-of-concept study showing that giving male mice a cyclic ketogenic diet reduced their midlife risk of death and prevented memory decline associated with normal aging.

“After reading two seminal papers published in 2017 that showed its beneficial roles in the overall health of aged mice, including brain performance, we decided to study the effect of the ketogenic diet,” Christian Gonza lez-Billault, professor at the Universidad de Chile, director of the Geroscience Center for Brain Health and Metabolism (GERO), and Adjunct Professor at The Buck Institute for Research on Aging, lead author of the new study on keto diets and aging, told Medical News Today.

“In these two [previous] works, the authors showed improvement in specific behavioral tasks routinely used in animal experimentation to evaluate memory and learning,” he continued.

“Such an improvement convinced us to go deeper into the molecular mechanisms that explain that positive response on one side, but also prompted us to include several other assessments at different levels, ranging from the whole organism level to the molecular functions, to understand why the diet was beneficial in aged animals,” added Gonza lez-Billault, who collaborated with Newman on the recent study.

The latest results from the team appear in Cell Reports Medicine.

To investigate the previous findings further, the researchers kept 19 male mice aged 20–23 months — counting as “old age” in mice — either on a control diet, or on a ketogenic diet cycled with the control diet every other week.

For the first 12, weeks the metabolic parameters of these mice were measured, and for 5 weeks after that, mice were kept on their diets and subjected to behavioral testing.

The results indicated that the ketogenic diet was associated with lower blood sugar, improved memory and motor ability in older mice. Researchers showed there was improved plasticity in the hippocampus brain region of older mice.

Further testing showed that this improved plasticity seen in mice kept on a ketogenic diet cycled with a control diet was due to a molecule called a ketone body, which is produced when levels of glucose are low, activated a signaling pathway between the synapses.

“We focus our attention on aged mice because previous work showed that the effect of the diet in young animals was milder and, in some cases, did not show significant differences with a control diet. These previous antecedents suggest that one of the beneficial roles of the diet would be maintaining resilience in aged mice, improving their physiological functions as they age,” said Gonza lez-Billault.

”This concept is fundamental in the aging field because it relates to the difference between lifespan (all our vital trajectory from when we are born until the day we die) and healthspan (the part of our vital trajectory free from chronic diseases),” he explained.

As for why keto diets do not appear to have the same effect in younger individuals, the researcher noted that:

“Why this is not happening when animals are younger still merits more studies. However, we could speculate that internal resilience mechanisms present while we are young are enough to compensate for or overcome damage induced in cells, tissues, organs, and the organism.”