Keto diets and aging: How might keto diets protect the aging brain?

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• 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.”

In addition to animal research, small studies in humans have suggested that the keto diet may benefit cognition, particularly in older adults with dementia.

The mechanisms might mirror those seen in animal studies, such as decreased inflammation, improved blood sugar control, and the potential of ketones to support brain function. However, the research is still in its early stages, and larger clinical studies are needed to confirm these potential benefits.

Beyond a lack of robust human research, one of the limitations of ketogenic diets is that they are hard to stick to, with many people struggling without carbohydrates in their diets.

With greatly reduced carb intake, ketogenic diets are also associated with reduced plant-based food intake. This can result in a lower intake of fiber, vitamins, minerals, and antioxidants that are important for overall health.

Instead of the keto diet, experts generally recommend that older adults follow diets supported by more extensive human research for healthy aging.

The Mediterranean and DASH diets are two of the most recommended and science-backed diets for healthy aging.

If a person is interested in trying a ketogenic diet, it is best to do so under the guidance of a physician or registered dietitian to ensure to ensure adequate nutrient intake and optimal health outcomes.

This study and previous studies have looked specifically at male mice.

“We decided to look first at the effects of the intervention in male mice because single-gender use increases the power of comparison; it does not allow us to scrutinize the impact on the overall population, which is part of the limitations of our study. However, the effects observed in this work merit further evaluation of the ketogenic diet’s impact on female mice,” explained Gonza lez-Billault.

Questions have been raised previously about the effectiveness of ketogenic diets in women as their metabolisms process fats differently to men. This is currently the focus of ongoing research.

What this means, however, is that the latest study is not only limited in its applicability to our understanding of ketogenic diets in humans, seeing that the current research was conducted in mice, but also in terms of its applicability across biological sexes, as this study was conducted in males only.

Further research into the findings is definitely warranted, Gonza lez-Billault agreed.

“Our next studies will delve into a better comprehension of the molecular mechanisms involved in the beneficial roles of the diet in aged mice. We want to understand whether these effects observed in the brain depend only on the brain itself or if some of the responses we evaluate are linked to more systemic effects or related to the function of other relevant organs. In addition, we want to understand better the metabolic changes that improve the brain’s functions at the cellular level,” he told us.

Other experts have also highlighted that, while, this study yielded interesting and fascinating findings, further research in humans is warranted to confirm these effects.

Catherine Rall, RDN, a registered dietitian based in Denver, CO, and certified nutritionist at Happy V, who was not involved in the research, commented that:

“This study suggests that repeatedly going on a short-term keto diet can have benefits to memory, motor function, and neuroplasticity, but doesn’t suggest any particular reason why. Notably, this study was done on male mice, so its applicability to humans, in general, and women, in particular, is limited.“