Calorie restriction is a type of diet that advocates reducing the amount of calories consumed, but in a safe way and without reaching a state of malnutrition or a lack of components that are required by the body, such as intermittent fasting. This diet is attributed to the effect of longevity, and although it is logical to think that such a diet will affect the digestive system or the accumulation of fat in the body, not many associate it with maintaining brain health and in particular with preventing diseases such as Alzheimer's.
In a study published on January 11, 2024, and conducted at the Buck Institute for the Study of Aging, it became clear that the OXR1 gene, which is necessary for a long and healthy life, is affected by this diet process, and is of great importance to the brain. The research team demonstrated the mechanism that caloric restriction applies at the cellular level, and how it can delay aging processes and cognitive decline in the brain.
The researchers have already shown in their previous studies different mechanisms that help extend human life with the help of nutritional restrictions, but regarding caloric restriction a very diverse response was seen both among people and in different tissues of their body. Therefore, it was decided to investigate this issue in more depth, and it began with experiments done on about 200 varieties of flies with different genetic backgrounds. All flies were raised on one of two diets: a normal diet or a calorically restricted diet of 10% of the flies' normal diet. The researchers identified 5 genes that affected the lifespan of the flies whose caloric intake was restricted, and among them there are 2 that are also equivalent to humans.
The team however chose to study one gene, the same OXR1, whose purpose is to protect the cells from oxidative damage, but its mechanism and the way it functions were not yet 100% clear to the researchers. A decrease in the amount of OXR1 in humans leads to severe neurological damage and premature death, and in mice, an excess of this gene helped improve their survival when dealing with amyotrophic lateral sclerosis (ALS).
To understand how a gene that is active in nerve cells affects a person's lifespan, the team conducted a series of tests. What was discovered is that the OXR1 gene affects a protein complex called a retromer, which is actually a collection of proteins that are necessary for the recycling of protein and lipids in cells. "The retromer is a mechanism that is very important for nerve cells, because it determines the fate of all the proteins that will reach these cells," says Kenneth Wilson, the lead author of the study.
Dysfunction of the retromer is linked to degenerative diseases that accompany old age, including Alzheimer's and Parkinson's. What this study actually showed is that the retromer can be trained to function more efficiently, with the help of calorie restriction in the diet. "By eating less, you will actually improve the mechanism of arranging the proteins in the cells in your body, which will significantly affect your brain in old age," says Wilson. The researchers even believe that the expression of this gene can actually extend life, because these are the results observed in the experiments conducted on the flies. "Our next step is to identify which compounds increase OXR1 levels and can help the brain to age more slowly," says Lisa Ellerbee, one of the authors of the study.
"We hope that after all this we can understand why our brains suffer from degeneration in the first place," says Wilson. "Nutrition affects various processes throughout the body, and I think our work will encourage people to maintain a healthier diet, because what you eat affects you more than you think."
