A pair of new studies find that diets termed ketogenic that are classically low in carbohydrates can prolong life in adult male laboratory mice. In addition this ketogenic diet also preserves the memory functions as well as muscle masses of the aged mice that were fed on it. The mechanism behind this could be the fact that ketogenic diet induces protein acetylation in the mice liver and muscles.
The findings were published yesterday, September 5 2017, in the journal Cell Metabolism. The studies were entitled “Ketogenic diet reduces mid-life mortality and improves memory in aging mice” by Newman and colleagues and “A ketogenic diet extends longevity and healthspan in adult mice” by Roberts and colleagues.
Keto food pyramid chart. Nutrition and diet infographics. Image Credit: Sudowoodo / Shutterstock
Researchers explain that restriction of calories without causing malnutrition leads to increase in the lifespan and the metabolism changes include beta oxidation leading to breakdown of fats compared to glycolysis or break down of sugars. This means that the body survives on the ketones that are produced on metabolism rather than sugars.
For these studies the researchers wanted to mimic the changes in metabolism that may be caused by low carbohydrate intake and check if it increases the lifespan of the mice. They too special strains of mice for their experiments termed C57BL/6 mice that were fed with three types of diets in three different groups - ketogenic, low-carbohydrate, or control diet when they were around 12 months of age. Some of these mice were allowed to live out their normal lifespan while some were tested for their functions and physiological changes after 1 or 14 months of the diet introduction.
The memory functions and health of the mice were checked using various tasks such as running wheels, mazes, balance beams etc. The aged mice were also tested for their heart function and gene regulation changes using RNA sequencing analysis. Genetic testing helped to understand the changes seen when a person is fasting in terms of insulin and its workings.
Results showed that ketogenic diets significantly increased the lifespan of the mice when compared to those on normal regular diets. Further the aged mice that were given ketogenic diet showed a higher protein acetylation level in their livers.
Eric Verdin, President and CEO of the Buck Institute for Research on Aging and senior author of one of the papers explained that older mice in the study showed better memory functions that younger mice when fed on ketogenic diets. This he claimed was “exciting” and is truly remarkable. Verdin said that there are two parts of the experiment that render it strong and its results robust. Both parts of the study show that there is a global positive effect on health span due to ketogenic diet he explained. One of the tests also showed that with ketogenic diet the older mice had a better preserved physical fitness and better grip strength.
Dr. Jon Ramsey, a professor at the University of California Davis and a senior author of the findings said that the team was impressed with the changes seen despite aging. In this study Megan Roberts and her colleagues found that a ketogenic diet produced a 13% longer life in mice that lived an average of 1003 days compared to 886 days average in mice that were given normal diet.
Ketogenic diet involves fasting and extremely low carbohydrates in diet. This stimulates the liver to produce ketones that can provide energy for the body and its organs especially the brain. This can be seen both during fasting as well as during exercising. In these experiments the carbohydrate levels in diet given to the mice was low and fats made up of 89%-90% of total calorie intake. Verdin explained that this diet kind of “reorganized” the whole of the metabolism. He warned that trying this diet could be risky. He said that the mice that ate ketogenic diet eventually would become obese. To prevent this, the team alternated between a ketogenic diet and a regular diet. Ramsey and colleagues in their experiment regulated the calories they gave to the mice to prevent weight gain. This difference in the methods to maintain body weight would explain the fact why in one study the mice were active in old age while the other study showed no such finding. Ramsey explained that they were looking for explanations by which these diets work that could help develop an ideal diet plan. Verdin added that this was a “difficult and drastic” diet to follow and the actual effects are far from being clear.