Researchers in the US have shown that a ketogenic diet, which is low in carbohydrates and protein but high in fats, improves healthspan and memory in aging mice.
Eating the diet ramps up the production of the ketone body beta-hydroxybutyrate acid (BHB). While small studies in humans with cognitive impairment have suggested that BHB could improve memory, senior scientist and Buck President and CEO, Eric Verdin MD, says this is the first study in aging mammals which details the positive effects of BHB on memory and lifespan.
“This opens up a new field in aging research,” said Verdin. “We think the health benefits of BHB may go beyond memory and could affect tissues and organ systems.” Verdin added that the results also support efforts in his lab to translate the findings to the clinic. “We’re looking for drug targets. The ultimate goal is to find a way for humans to benefit from BHBs without having to go on a restrictive diet.”
The ketogenic diet-fed mice had a lower risk of dying as they aged from one to two years old, although their maximum lifespan was unchanged. Another group of mice underwent memory testing at both middle age (one year old) and old age (two years old).
Mice that had been eating a ketogenic diet performed at least as well on memory tests at old age as they did at middle age, while mice eating the normal diet showed an expected age-associated decline.
Mice who ate the ketogenic diet also explored more, and their improved memory was confirmed with another test a few months later. Newman noted that the mice were off the ketogenic diet and did not have any BHB in their blood during the testing period.
Mice which are allowed to remain on the ketogenic diet will eventually become obese.
“We were careful to have all of the mice eating a normal diet during the actual memory testing which suggests the effects of the ketogenic diet were lasting. Something changed in the brains of these mice to make them more resilient to the effects of age,” he said. “Determining what this is, is the next step in the work.”
Verdin said the study will open the door to new therapies for the cognitive problems of aging. “As we gain a deeper understanding of what BHB does in our body and our brain, we can intelligently design therapies to capture individual benefits while minimizing harms.” The Verdin lab is currently exploring beneficial effects of a similar ketogenic diet in a mouse model of Alzheimer’s disease.
Results of the study from Eric Verdin’s lab at the Buck Institute for Research on Aging in Novato, CA are published in the September 5th issue of Cell Metabolism.