Eating Less Shown to Significantly Boost Lifespan and Slow Down Brain Aging

Scientists at the Buck Institute have made a significant discovery in the realm of cognitive health, brain aging, and longevity. Their study delved into the effects of dietary restriction, or eating less, on slowing cognitive decline and prolonging human lifespan.

The researchers pinpointed a neuron-specific response controlled by a gene called OXR1, which gets boosted by practices like intermittent fasting and low-calorie diets.

Dr. Kenneth Wilson, the first author of the study, highlighted, “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. As it turns out, this is a gene that is important in the brain.”

How Eating Less Helps You Live Longer

The study, utilizing fruit flies and human cells, uncovered the mechanisms through which dietary restriction hinders aging and slows the progression of neurodegenerative brain diseases.

“We found a neuron-specific response that mediates the neuroprotection of dietary restriction,” said Professor Pankaj Kapahi. “Strategies such as intermittent fasting or caloric restriction, which limit nutrients, may enhance levels of this gene to mediate its protective effects.”

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

While it was known that dietary restriction improves lifespan and health span, the researchers sought to understand the variations in response across individuals and tissues.

Scanning around 200 fly strains with diverse genetic backgrounds and diets, they identified five genes, two of which had human counterparts, significantly influencing longevity under dietary restriction.

Dietary Restriction and Brain Health

Focusing on the "mustard" (mtd) gene in fruit flies and its human equivalent, OXR1, researchers explored its role in shielding cells from oxidative damage.

The loss of OXR1 in humans leads to severe neurological defects and early death, while excess in mice enhances survival in ALS models.

Further investigations highlighted the connection between brain aging, neurodegeneration, and lifespan. OXR1 was found to impact the retromer complex, crucial for recycling cellular proteins and lipids and maintaining neurons.

“The retromer is an important mechanism in neurons because it determines the fate of all proteins brought into the cell,” stated Wilson. Retromer dysfunction is linked to age-related brain issues, which dietary restriction can protect against.

Findings and Implications

Kapahi’s team revealed the crucial role of dietary habits in brain health and longevity. Their findings center on the discovery that dietary restriction significantly slows brain aging, mainly through the activity of the mtd/OXR1 gene, critical for maintaining the retromer pathway.

Kapahi emphasizes, “This work shows that the retromer pathway, instrumental in reusing cellular proteins, is essential in protecting neurons under conditions of limited nutrients.”

The research indicates that mtd/OXR1 is vital for preserving retromer function and maintaining neuronal health, promoting healthy brain aging, and extending lifespan under dietary restrictions.

Exploring the impact of diet on this gene, Wilson notes, “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.”

Eat Less, Stay Smart, and Live Longer

The research also found that increasing mtd levels in flies extended their lifespan, hinting at potential life-extending benefits in humans with increased OXR1 expression.

The study suggests that dietary choices profoundly affect cellular health, brain functionality, and longevity.

“Our next step is to identify specific compounds that increase the levels of OXR1 during aging to delay brain aging,” reveals Ellerby, hinting at potential therapeutic developments.

Wilson reflects on the broader implications, stating, “Hopefully from this, we can get more of an idea of why our brains degenerate in the first place.” This underscores the quest for a deeper understanding of brain aging processes.

In conclusion, Wilson emphasizes the overall impact of diet, “Diet impacts all the processes in your body. I think this work supports efforts to follow a healthy diet because what you eat will affect more than you know.”

This statement serves as a reminder of the far-reaching consequences of dietary choices, not just for brain health but for overall well-being. The study is published in the journal Nature Communications.

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