Unlock the Secret to Slowing Brain Aging: This Diet Gene May Extend Lifespans

NOVATO, Calif. — The right diet can slow brain aging and add years to your life. Now, scientists know why. Researchers at the Buck Institute have discovered a significant connection between calorie restriction, brain health, and increased lifespan — all focusing on the gene OXR1.

“When people restrict the amount of food that they eat, they typically think it might affect their digestive tract or fat buildup, but not necessarily about how it affects the brain,” says Kenneth Wilson, PhD, a Buck Institute postdoc and first author of the study. “As it turns out, this is a gene that is important in the brain.”

The study, which involved fruit flies and human cells, reveals that dietary restriction can delay aging and slow the progression of neurodegenerative diseases, like Alzheimer’s and Parkinson’s, through a specific cellular mechanism. This process is primarily facilitated by the OXR1 gene, which plays a vital role in protecting brain cells from aging and causing neurological disorders.

“We found a neuron-specific response that mediates the neuroprotection of dietary restriction,” notes Buck Professor Pankaj Kapahi, PhD, co-senior author of the study, in a media release. “Strategies such as intermittent fasting or caloric restriction, which limit nutrients, may enhance levels of this gene to mediate its protective effects.”

“The gene is an important brain resilience factor protecting against aging and neurological diseases,” adds Buck Professor Lisa Ellerby, PhD, co-senior author of the study.

The researchers’ journey began with the study of about 200 strains of fruit flies under different diets. They discovered that specific genetic variants, including the OXR1 gene (known as “mustard” or “mtd” in fruit flies), significantly influenced longevity under calorie-restricted diets. Scientists have found that this gene also protects cells from oxidative damage, which can lead to severe neurological defects and premature death.

Interestingly, the team found that the OXR1 gene impacts a protein complex called the retromer, essential for recycling cellular proteins and lipids.

“The retromer is an important mechanism in neurons because it determines the fate of all proteins that are brought into the cell,” says Wilson.

This process is particularly crucial in neurons and has a link to the prevention of age-related neurodegenerative diseases. The study authors conclude that dietary restriction aids in maintaining the retromer’s ability to function, ensuring healthy brain aging and extending lifespan.

“Diet is influencing this gene. By eating less, you are actually enhancing this mechanism of proteins being sorted properly in your cells, because your cells are enhancing the expression of OXR1,” Wilson explains.

Looking forward, the researchers want to identify compounds that can increase OXR1 levels in humans, potentially delaying brain aging and adding years to people’s lives.

“Hopefully from this we can get more of an idea of why our brains degenerate in the first place,” Wilson concludes. “Diet impacts all the processes in your body. I think this work supports efforts to follow a healthy diet, because what you eat is going to affect more than you know.”

The groundbreaking study is published in the journal Nature Communications.

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