• As we get older, our brain naturally ages, and the ability to perform certain tasks like memory and learning declines.
  • Previous research shows that living a healthy lifestyle that includes eating right can help slow brain aging.
  • Researchers from the Buck Institute for Research on Aging have found that restricting the amount of food a person eats may also help protect the brain from aging.
  • The research identified a specific gene that is enhanced through calorie restriction, aiding processes necessary for healthy brain aging.

As we get older, our body — including our brain — naturally begins to age. Certain tasks that the brain performs, such as memory and learning, begin to decline.

According to the National Institute on Aging, previous research shows that living a healthy lifestyle that includes physical activity, stress management, fostering social connections, and eating right, can help slow brain aging.

Now researchers from the Buck Institute for Research on Aging in Novato, CA, have found that restricting the amount of food a person eats may also help protect the brain from aging, via models of both fruit flies and human cells.

The research — recently published in the journal Nature Communications — identified a specific gene that is enhanced through calorie restriction, aiding processes necessary for healthy brain aging.

According to Dr. Lisa Ellerby, professor at the Buck Institute for Research on Aging, adjunct professor of gerontology at the USC Leonard Davis School of Gerontology, and co-senior author of this study, the team decided to study the impact of calorie restriction on brain aging because dietary restriction is a significant intervention for the aging process and the brain is a particularly vulnerable organ during aging.

“Therefore, understanding factors that are modulated by dietary restriction and are protective in the brain is a significant research direction in the field,” Dr. Ellerby told Medical News Today. “Plus, many people are doing various forms of caloric restriction, in particular, intermittent fasting. This was a beginning step in understanding how those efforts might impact brain aging.”

For example, a review of research published in February 2021 reported that dietary restriction may help protect the brain against neuroinflammation and neurodegeneration.

“Age-related disease is arguably the greatest biomedical challenge in the 21st century,” Dr. Ellerby said.

“Age is the largest risk factor for developing diseases of the brain. Postponing or decreasing the rate of aging could retard multiple age-related diseases and thus neurological diseases. In terms of Alzheimer’s and Parkinson’s disease, there are no available treatments to actually treat the diseases, so it’s important that we understand ways to prevent or slow the progression of neurodegenerative diseases.”

– Dr. Lisa Ellerby

For this study, Dr. Ellerby and her team used both fruit fly models and human cells to examine how calorie restriction might affect how the brain ages.

The team used a fruit fly model of 160 different fly strains with different genetic backgrounds. Flies were either raised on a normal diet or a diet that was only 10% of its normal nutrition.

From there, researchers identified five genes that had specific variants that significantly impacted longevity under dietary restriction.

One of those is the “mustard” gene in fruit flies that correlates to the oxidation resistance 1 (OXR1) gene in humans and rodents.

Previous research shows that a depletion of OXR1 gene products is a shared feature of neurodegenerative conditions like Parkinson’s disease and diabetic retinopathy, while studies in mice show that overexpression of OXR1 may be protective against amyotrophic lateral sclerosis (ALS).

Additionally, scientists found the OXR1 gene affects the retromer, which sorts proteins and decides which can be reused by the body and which cannot.

“Recycling is important in our daily life,” Dr. Ellerby explained. “A cell does a similar process — it needs to recycle damaged components. The retromer is a cellular complex known to recycle proteins and lipids.”

“It was surprising [that] a protein known as OXR1 [expressed by the OXR1 gene] is involved in the retromer function,” she continued. “In past research, this protein was thought to be involved in responding to oxidative stress or detoxification.”

Dr. Ellerby said she and her colleagues believe these findings may be used in the future to help identify potential therapeutic targets to potentially slow aging and age-related neurodegenerative diseases.

“Finding factors that make the brain resilient or prevent the aging process will be important to slowing aging,” she continued. “It is possible that simple changes in our diet can increase the levels of OXR1 in the brain and this would be protective.”

“We boosted OXR1 in the flies via genetic manipulation,” Dr. Ellerby added. “We are planning to identify small molecules that increase the expression of OXR1 to design a therapeutic for the aging brain.”

MNT also spoke with Dr. Clifford Segil, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, about this study.

After reading this research, Dr. Segil commented that it remains challenging to elucidate which findings can translate into providing neurologists with something to advise their patients to do to promote healthy eating.

“Dietary restriction was noted to have clear mechanisms of action with enhanced metabolism and fat burning with age and dietary restriction in the brain is something that should be pursued in more complicated organisms than fruit flies and yeast, though the research has to start in these simple organisms,” he explained.

“Dietary and caloric restriction, I believe, are worthy of further studies to determine if our excessive cultural caloric intake provides us with more harm than benefits. A healthy diet decreases the [chances] of having a stroke or cerebrovascular disease also,” added Dr. Segil.

He further pointed out that, with the current trend of injectable medications being used on a widespread basis for weight loss, large numbers of people are going to be effectively diet-restricted.

“This cohort may be an excellent group to use as data in future research to determine what dietary restriction can do to help avoid neurodegenerative diseases like Alzheimer’s or Parkinson’s disease,” he added.

“I would like a bench [of] scientists to take the results from this study and use it in more complicated organisms than fruit flies and yeasts. I would like to see this group of scientists collaborate with another group of scientists who could use human patients using injectable weight loss medications — GLP-1 agents — to design a study with human clinical data,” said Dr. Segil.

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