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Scientists from the Buck Institute for Research on Aging have identified a crucial gene, OXR1, that plays a pivotal role in extending lifespan and promoting healthy brain aging through dietary restriction.

This breakthrough, published in Nature Communications, not only sheds light on the long-standing mystery of how caloric restriction benefits the brain but also opens new avenues for potential treatments against neurodegenerative diseases.

Kenneth Wilson, Ph.D., a postdoctoral researcher at Buck and the first author of the study, emphasized the surprising impact of diet on brain health.

"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," he was quoted as saying by Medical Xpress.

The gene OXR1, previously underappreciated in brain function, has now been shown to be a critical player in neuronal health and longevity.

The Buck Institute team, including co-senior authors Professors Pankaj Kapahi, Ph.D., and Lisa Ellerby, Ph.D., demonstrated how dietary restriction triggers a neuron-specific response that underpins neuroprotection.

Their research, conducted on fruit flies and human cells, revealed that the gene 'mustard' (mtd) in fruit flies and its human and mouse counterpart, OXR1, is integral in protecting cells from oxidative damage.

A series of in-depth tests unveiled that OXR1 affects the retromer complex, 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," Wilson explained.

This discovery is particularly significant as retromer dysfunction is linked to age-related neurodegenerative diseases, such as Alzheimer's and Parkinson's, which dietary restriction has been shown to protect against.

The variability in response to dietary restriction, a focal point of the study, was explored by examining around 200 strains of fruit flies with different genetic backgrounds on varied diets.

The researchers identified five genes, including mtd/OXR1, which significantly affected longevity under dietary restriction. Intriguingly, boosting mtd in flies led to increased lifespan, suggesting that enhanced OXR1 expression in humans might also promote longevity.

"Our next step is to identify specific compounds that increase the levels of OXR1 during aging to delay brain aging," stated Ellerby, highlighting the future direction of their research.

This groundbreaking study not only underscores the profound impact of diet on brain health and aging but also suggests that dietary choices may have more far-reaching effects than previously understood.

"Diet impacts all the processes in your body," Wilson concluded. "I think this work supports efforts to follow a healthy diet, because what you eat is going to affect more than you know."

As researchers continue to unravel the complexities of aging and neurodegeneration, this study marks a significant advancement in understanding the interplay between genetics, diet, and brain health.