- Research has already shown that ketogenic diets can improve brain performance in older male mice.
- Now, the authors of a new study in mice have identified a particular mechanism that could be behind this phenomenon.
- The research raises questions about the role of diet in aging and brain health.
Researchers have discovered a potential mechanism behind the improvements seen in aging male mice on a ketogenic diet – “keto diets,” for short.
They proposed that switching male mice between a control diet and a ketogenic diet led to an improvement in the signaling that occurs between synapses in the brain.
Previously, John Newman, MD, PhD, one of the authors of the paper, published a validation study showing that giving male mice a cyclical ketogenic diet reduced their risk of death in midlife and prevented decline in memory associated with normal aging.
“After reading two seminal articles published in 2017 which showed its beneficial roles on the overall health of aged mice, including on brain performance, we decided to study the effect of the ketogenic diet”, Christian Gonza lez-Billault, professor at the University of Chile. , director of the Geroscience Center for Brain Health and Metabolism (GERO) and assistant professor at the Buck Institute for Research on Aging, lead author of the new study on keto diets and aging, said Medical news today.
“In these two (previous) works, the authors showed improvement in specific behavioral tasks commonly used in animal testing to assess memory and learning,” he continued.
“Such improvement convinced us to delve deeper into the molecular mechanisms that explain this positive response on one side, but also prompted us to include several other assessments at different levels, ranging from the whole organism level to 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 team’s latest results appear in Cell Reports Medicine.
To expand on previous findings, the researchers kept 19 male mice aged 20 to 23 months – counting as “old age” in mice – either on a control diet or on a ketogenic diet alternating with the control diet every two weeks.
During the first 12 weeks, the metabolic parameters of these mice were measured, then for 5 weeks, the mice were maintained on a diet and subjected to behavioral tests.
The results indicated that the ketogenic diet was associated with lower blood sugar, improved memory and motor skills in older mice. The researchers showed improved plasticity in the hippocampus brain region of older mice.
Further testing showed that this enhanced plasticity observed in mice fed a ketogenic diet followed by a control diet was due to a molecule called ketone bodies, which are produced when glucose levels are low, activating a signaling pathway between the synapses.
“We are focusing our attention on aged mice because previous work has shown that the effect of diet in young animals was milder and, in some cases, did not show significant differences with a control diet. This background suggests that one of the beneficial roles of diet would be to maintain resilience in aged mice, thereby improving their physiological functions as they age,” said Gonza lez-Billault.
“This concept is fundamental in the field of aging because it concerns the difference between the lifespan (our entire life trajectory from our birth until the day of our death) and the health lifespan (the part of our life trajectory free from chronic diseases),” he said. explain.
As for why keto diets don’t seem to have the same effect in younger individuals, the researcher noted that:
“Why this doesn’t happen when the animals are younger deserves further study.” However, we could speculate that the internal resilience mechanisms present when we are young are sufficient to compensate or overcome the damage induced in cells, tissues, organs and the organism.
In addition to animal research, small human studies have suggested that the keto diet may benefit cognition, particularly in older adults with dementia.
The mechanisms could mirror those seen in animal studies, such as decreased inflammation, better blood sugar control, and the potential of ketones to support brain function. However, research is in its early stages and larger clinical studies are needed to confirm these potential benefits.
Beyond the lack of solid human research, one of the limitations of ketogenic diets is that they are difficult to stick to, with many people having difficulty going without carbohydrates in their diet.
Along with significantly reduced carbohydrate intake, ketogenic diets are also associated with reduced plant-based food intake. This can lead to a decreased 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 backed by more extensive human research for healthy aging.
The Mediterranean and DASH diets are two of the most recommended and science-backed diets.
If a person wants to try a ketogenic diet, it is best to do so under the guidance of a doctor or registered dietitian to ensure adequate nutritional intake and optimal health results.
This and previous studies looked specifically at male mice.
“We decided to first examine the effects of the intervention in male mice, because use by only one sex increases the power of comparison; this does not allow us to examine the impact on the overall population, which is one of the limitations of our study. However, the effects observed in this work merit further evaluation of the impact of the ketogenic diet on female mice,” explains Gonza lez-Billault.
Questions have previously been raised about the effectiveness of ketogenic diets in women because their metabolism processes fat differently than men. This is currently the subject 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, given that the current research was conducted on mice, but also in terms of ‘applicability to all biological sexes, as this study was conducted only among men.
Further research into the findings is certainly warranted, Gonza lez-Billault agreed.
“Our next studies will aim to better understand the molecular mechanisms involved in the beneficial roles of diet in aged mice. We want to understand if these effects observed in the brain depend solely on the brain itself or if some of the responses we evaluate are linked to more systemic effects or linked to the functioning of other organs involved. Additionally, we want to better understand the metabolic changes that improve brain function at the cellular level,” he told us.
Other experts also pointed out that although this study yielded some interesting and fascinating results, more research in humans is needed to confirm these effects.
Catherine Rall, RDN, a registered dietitian based in Denver, Colorado, and certified nutritionist at Happy V, who was not involved in the research, commented that:
“This study suggests that following a keto diet short-term and repeatedly may have beneficial effects on memory, motor function, and neuroplasticity, but does not suggest any specific reason. Notably, this study was carried out on male mice, so its applicability to humans in general and women in particular is limited.