Eating less food is proven to dramatically increase lifespan • Earth.com

Scientists at the Buck Institute have made a breakthrough discovery in the field of cognitive health, brain aging and longevity. The study focused on the role of dietary restriction (eating less) in slowing cognitive decline and extending human lifespan.

The experts identified a neuron-specific response mediated by a gene called OXR1, which is enhanced by strategies like intermittent fasting and low-calorie diets. 

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

How eating less helps you live longer

The research, conducted using fruit flies and human cells, has revealed how dietary restriction delays 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.”

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

While the Buck team had previously established that lifespan and healthspan can be improved with dietary restriction, they found a lot of variability in response to reduced calories across individuals and different tissues. The current study was initiated to investigate the reasons for this variability.

The experts scanned about 200 strains of flies with varying genetic backgrounds and diets. They identified five genes, including two with human genetic 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, the researchers explored its role in protecting cells from oxidative damage.

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

The connection between brain aging, neurodegeneration, and lifespan was further investigated through in-depth tests.  

OXR1 was found to impact the retromer complex, which is crucial for recycling cellular proteins and lipids and maintaining neurons.

This pathway is vital in protecting neurons under nutrient limitations, as confirmed by the team’s findings. 

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

Retromer dysfunction is linked to age-related brain problems, including Alzheimer’s and Parkinson’s diseases, which dietary restriction can protect against.

Findings and implications

The research led by Kapahi’s team revealed the pivotal role of dietary habits in brain health and longevity. Their findings hinge on the discovery that dietary restriction significantly slows brain aging.

This occurs primarily through the activity of a gene known as mtd/OXR1, which plays a crucial role in maintaining the retromer – a cellular pathway involved in recycling proteins.

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

The team’s research indicates that mtd/OXR1 is vital not only for preserving retromer function but also for maintaining neuronal health, promoting healthy brain aging, and extending lifespan under dietary restrictions.

Further 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, live longer

The team’s research also discovered that increasing mtd levels in flies led to an extended lifespan. This finding has led researchers to speculate that in humans, increased expression of OXR1 might have similar life-extending benefits.

In summary, the study’s revelations suggests that dietary choices have a profound impact on our 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, indicating the potential for future therapeutic developments.

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

In his concluding remarks, Wilson emphasizes the overarching 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 is going to affect more than you know.”

This statement serves as a reminder of the far-reaching consequences of our 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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