The ketogenic diet has both supporters and critics among people who are trying to lose weight, but regardless, the diet has been proven to have an effect on memory in mice. Scientists have discovered that the high fat, low carbohydrate diet enhances memory in older mice, and they have also identified a new molecular signaling pathway that improves synapse function. This new finding helps to explain the diet’s positive impact on brain health and aging.mice. Scientists from Buck Institute and the University of Chile have discovered a new molecular signaling pathway that enhances synapse function. This helps to explain how the ketogenic diet can benefit brain health and slow down the aging process. The study was published in the June 5, 2024 issue of Cell Reports Medicine. These findings open up new possibilities for targeting memory improvement on a molecular level, without the need for following a ketogenic diet or its byproducts.
“Our research shows that the ketogenic diet has wide-ranging benefits for brain function. We have also identified a mechanism of action that can be used as a strategy to maintain and enhance cognitive function, without the need for following the ketogenic diet or its byproducts,” said the researchers.The study’s senior author, Christian González-Billault, PhD, stated that this function is important during aging. He is a professor at the Universidad de Chile and director of their Geroscience Center for Brain Health and Metabolism, and adjunct professor at the Buck Institute.
John Newman, MD, PhD, who collaborated with Dr. González-Billault on the study, mentioned that their previous work showed a ketogenic diet improving healthspan and memory in aging mice. The new work indicates that they can start with older animals and still improve the health of the aging brain, and that the changes begin to happen relatively quickly..Newman is both a faculty member at the Buck Institute and a geriatrician at the University of California, San Francisco. “This study is the most comprehensive examination of the ketogenic diet’s effects on the aging brain in mice to date.”
Over a century ago, scientists observed that rats that consumed fewer calories lived longer. “We now understand that the ability to manipulate lifespan is not solely about eating less,” Newman explained, “but rather, it is linked to internal cellular signals that regulate specific pathways in response to available nutrients. Many of these pathways are associated with aging, such as controlling protein turnover and metabolism.”One of the signals is the presence of ketone bodies, including acetoacetate (AcAc), β-hydroxybutyrate (BHB), and acetone, which are produced in the liver. These molecules increase when there is a shortage of glucose, caused by factors such as caloric restriction, intense exercise, or a low carbohydrate intake, as seen in a ketogenic diet.
Seven years ago, Newman and his team proved that exposing mice to increased levels of ketone bodies through a ketogenic diet can help them live longer and age in a healthier way. This had a significant impact on their overall health.”One of the most interesting findings from the study was that as mice on a ketogenic diet aged, their memory was preserved, and possibly even improved compared to when they were younger,” stated the researcher.
The study, which aimed to determine the specific components of the ketogenic diet that were responsible for this effect and how they were impacting the brain on a molecular level to enhance memory, was led by González-Billault in collaboration with other scientists at the Buck Institute. In the study, mice on a ketogenic diet were fed a diet consisting of 90 percent fat and 10 percent protein, while those on a control diet received the same amount of protein but only 13 percent fat. The “advanced age” mice, which were over two years old, were given one week of the ketogenic diet.The mice were fed a ketogenic diet for one week, followed by a week of the control diet to prevent overeating and obesity.
González-Billault demonstrated the benefits of the ketogenic diet through neurophysiological and behavioral experiments with aged mice. These experiments tested the effectiveness of memory generation, storage, and retrieval mechanisms. The results indicated that the ketogenic diet improved the functioning of the synapses responsible for memory. This led to a detailed examination of the protein composition at these synapses in the hippocampus, in collaboration with Buck professors.Professor Birgit Schilling, PhD, who leads the Proteomics and Mass Spectrometry Center, expressed her astonishment at the significant impact of the ketogenic diet on synaptic proteins. The changes were observed after just one week on the diet and became more pronounced over time, with testing after six weeks and a year. Additionally, the team found that the ketogenic diet activated a specific signaling pathway (protein kinase A) critical to synapse activity in isolated cells.It was demonstrated that BHB, the primary ketone body generated in a ketogenic diet, activates this pathway. This suggests that ketone bodies, especially BHB, play a critical role not only as an energy source but also as a signaling molecule. “BHB is likely not the sole molecule involved, but we believe it is a significant aspect in understanding the mechanisms of the ketogenic diet and ketone bodies,” Newman stated. “This study is the first to truly link the intricate molecular mechanisms of ketone bodies to the improvement of the aging brain.” Moving forward, the next phase will focus on It , worth investigating if similar memory protection can be achieved by using BHB alone, or possibly by even more specific manipulation of the protein kinase A signaling pathway. The goal would be to recreate the overall effects on synapse function and memory by targeting the signaling pathway in the correct cells. This could potentially eliminate the need for a ketogenic diet in the future.
