A new study uncovers the significant benefits of the ketogenic diet on memory and brain health in aging mice. Researchers identified a molecular signaling pathway that may hold the key to these improvements. Published in Cell Reports Medicine, this study could reshape approaches to cognitive health in aging.
The ketogenic diet, known for its high-fat, low-carbohydrate composition, may have a remarkable impact on memory and brain health, according to a new study published in the journal Cell Reports Medicine. Scientists from the Buck Institute for Research on Aging and the University of Chile have discovered a novel molecular signaling pathway activated by this diet, which significantly enhances synaptic function and memory in aging mice.
“Our work indicates that the effects of the ketogenic diet benefit brain function broadly, and we provide a mechanism of action that offers a strategy for the maintenance and improvement of this function during aging,” Christian González-Billault, the study’s senior author and professor at the Universidad de Chile and adjunct professor at the Buck Institute, said in a statement.
This discovery builds on previous research led by the Buck Institute, which demonstrated that a ketogenic diet could extend the healthspan and memory in aging mice.
“Building off our previous work showing that a ketogenic diet improves healthspan and memory in aging mice, this new work indicates that we can start with older animals and still improve the health of the aging brain, and that the changes begin to happen relatively quickly,” John Newman, an assistant professor at the Buck Institute and geriatrician at UC San Francisco, said in the statement.
Historical Context and New Findings
More than a century ago, it was noted that caloric restriction led to longer lifespans in animals. Today, scientists understand that this is not merely due to eating less but involves cellular signals that regulate aging-related pathways. Central to these signals are ketone bodies, produced during states of low carbohydrate intake, such as in a ketogenic diet.
Seven years ago, Newman’s team showed that a ketogenic diet could help mice live longer and maintain better cognitive functions.
“The most striking effect on their health as they aged was that their memory was preserved; it was possibly even better than when they were younger,” Newman said.
The current study aimed to dissect which components of the ketogenic diet influenced brain health and how. Mice over two years old were fed alternating weeks of a ketogenic diet and a control diet to avoid overeating and obesity. Results from neurophysiological and behavioral tests indicated substantial improvements in memory functions.
A deeper look into the brain’s synaptic proteins revealed that the ketogenic diet altered protein composition dramatically.
“Surprisingly, we saw that the ketogenic diet caused dramatic changes in the proteins of the synapse,” said Birgit Schilling, who led the proteomic analysis at the Buck Institute.
Furthermore, the team identified that the ketogenic diet activated the protein kinase A (PKA) signaling pathway in synapses, driven primarily by β-hydroxybutyrate (BHB), a key ketone body. This discovery underscores the potential of BHB not only as an energy source but also as a critical signaling molecule.
Future Implications
Looking forward, researchers plan to investigate if memory protection can be achieved by targeting the PKA signaling pathway directly or through BHB supplementation.
“If we could recreate some of the big-picture effects on synapse function and memory just by manipulating that signaling pathway in the right cells, we wouldn’t even need to eat a ketogenic diet in the end,” Newman said.