April 20, 2024
Brain Aging

Scientists Discover How Restricting Calories Slows Brain Aging and Increases Lifespan

In a recent study conducted by the Buck Institute for Research on Aging, scientists have identified a gene called OXR1 that plays a crucial role in the lifespan extension and protection against brain aging observed in individuals who practice dietary restriction. While the health benefits and increased lifespan associated with calorie restriction have been known for some time, the specific mechanisms through which it affects brain health have remained elusive.

Kenneth Wilson, Ph.D., a postdoc at the Buck Institute and the lead author of the study, emphasized that when people think about the impact of dietary restriction, they often focus on its effects on digestion and weight. However, this research reveals that the gene OXR1 is particularly significant for maintaining brain health.

The study also unveils the intricate cellular mechanisms by which dietary restriction can delay aging and slow down the progression of neurodegenerative diseases. The researchers conducted their experiments using fruit flies and human cells, successfully identifying potential therapeutic targets for slowing down the aging process and age-related neurological conditions.

Commenting on the findings, one of the co-senior authors of the study, Buck Professor Pankaj Kapahi, Ph.D., highlighted the discovery of a neuron-specific response that mediates the neuroprotective effects of dietary restriction. According to Kapahi, strategies such as intermittent fasting and caloric restriction may elevate the levels of the OXR1 gene, thereby enhancing its protective capabilities.

The researchers concluded that the OXR1 gene is a crucial factor in maintaining resilience against brain aging and neurological diseases. Lisa Ellerby, Ph.D., another co-senior author of the study, acknowledged that while previous research has showcased the mechanisms through which dietary restriction can enhance lifespan and healthspan, there is still considerable variability in individuals’ responses to calorie reduction. This study aimed to shed light on the reasons behind these differences.

The research team initially examined around 200 strains of fruit flies with different genetic backgrounds. The flies were subjected to two different diets: a normal diet and a restricted diet that consisted of only 10% of the regular nutrition. Through their analysis, the scientists identified five genes, two of which were linked to human genetics, that significantly affected longevity under dietary restriction.

Of these genes, the team focused on one called mustard (mtd) in fruit flies and Oxidation Resistance 1 (OXR1) in humans and mice. this gene primarily protects cells from oxidative damage, but its precise mechanism of action was not fully understood. However, the loss of OXR1 in humans leads to severe neurological defects and premature death, while delivering extra OXR1 in mice improves survival in a model of amyotrophic lateral sclerosis (ALS).

To delve deeper into the effects of the OXR1 gene on overall lifespan, the scientists conducted a series of comprehensive tests. Their analysis revealed that the gene influences a complex known as the retromer, which comprises proteins essential for recycling cellular proteins and lipids.

According to Wilson, the retromer plays a critical role in neurons as it determines the fate of all the proteins that enter the cell. Dysfunction in the retromer has been associated with age-related neurodegenerative diseases like Alzheimer’s and Parkinson’s, which are protected by dietary restriction.

Overall, the study demonstrates how dietary restriction slows down brain aging through the actions of mtd/OXR1 in preserving retromer function. According to Kapahi, this research highlights the importance of the retromer pathway, which is involved in reusing cellular proteins, in protecting neurons when nutrient availability is limited. Moreover, the team discovered that mtd/OXR1 is essential for neuronal function, healthy brain aging, and the lifespan extension observed with dietary restriction.

Notably, the study also revealed that increasing mtd in fruit flies resulted in longer lifespans, leading the researchers to speculate that excess expression of OXR1 in humans could potentially extend lifespan. Ellerby indicated that their next steps involve identifying specific compounds that can increase OXR1 levels during aging to delay brain aging. The ultimate goal, according to Wilson, is to gain a better understanding of the underlying causes of brain degeneration.

In conclusion, this study underscores the profound impact that diet has on various biological processes within the body. Wilson emphasized the importance of maintaining a healthy diet, as it can have far-reaching effects beyond what is commonly known. The findings of this research not only contribute to our understanding of the positive effects of calorie restriction but also offer potential avenues for interventions that can delay brain aging and improve overall healthspan.

1. Source: Coherent Market Insights, Public sources, Desk research
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