Consume Less, Live Longer: Eating Less Boosts Lifespan and Enhances Brain Health

In a recent study, researchers have unveiled a groundbreaking revelation about the connection between dietary restriction, brain health, and aging. The key player in this discovery is the OXR1 gene, which plays a critical role in prolonging lifespan and ensuring the aging process of the brain remains healthy, especially when subjected to dietary restrictions.

Through extensive investigations involving fruit flies and human cells, scientists have pinpointed the OXR1 gene's significance in safeguarding neurons and preserving the function of the retromer, a complex responsible for recycling cellular proteins. This newfound understanding of OXR1's involvement in neuronal protection sheds light on potential therapeutic interventions for age-related neurodegenerative diseases and strategies for extending lifespan.

Here are some key facts emerging from this research:

The OXR1 gene is indispensable for reaping the benefits of extended lifespan through dietary restriction, with a specific emphasis on maintaining brain health as one ages.

Studies have demonstrated that OXR1 plays a crucial role in influencing the retromer complex. This complex is essential for recycling cellular proteins, contributing significantly to overall neuronal function and health.

The research, which involved both fruit flies and human cells, not only enhances our understanding of OXR1 but also proposes promising avenues for the development of new treatments targeting neurodegenerative diseases associated with aging and strategies for promoting healthy aging.

In essence, this breakthrough discovery regarding the OXR1 gene opens up exciting possibilities for advancing our knowledge of brain health, aging, and potential interventions to enhance both. As scientists delve deeper into these findings, the prospect of healthier aging and combating neurodegenerative diseases becomes more promising.

Researchers at the Buck Institute have made a groundbreaking discovery shedding light on the connection between restricting calories and its positive impact on health and lifespan. While the benefits of calorie restriction have long been acknowledged, the specific mechanisms, especially in safeguarding the brain, have remained elusive. The scientists at Buck have identified a crucial player in this process – a gene known as OXR1.

Kenneth Wilson, Ph.D., a postdoc at Buck and the first author of the study, emphasized that when people cut back on food, they generally consider its effects on the digestive system or fat accumulation, not necessarily thinking about the impact on the brain. However, the study published on January 11, 2024, in Nature Communications reveals that OXR1 plays a vital role in the brain, making it essential for healthy brain aging.

The researchers not only uncovered the significance of OXR1 but also elucidated the intricate cellular mechanism through which dietary restriction can impede aging and slow the progression of neurodegenerative diseases. The study, conducted on fruit flies and human cells, also pinpointed potential targets for therapeutic interventions aimed at slowing aging and age-related neurodegenerative conditions.

Professor Pankaj Kapahi, Ph.D., a co-senior author of the study, highlighted a neuron-specific response that underlies the neuroprotection observed with dietary restriction. Strategies like intermittent fasting or caloric restriction, which limit nutrients, may boost the levels of OXR1, thereby enhancing its protective effects.

OXR1 emerged as a critical factor in promoting brain resilience against aging and neurological diseases, according to Professor Lisa Ellerby, Ph.D., another co-senior author of the study.

The team's earlier work had revealed mechanisms enhancing lifespan and healthspan through dietary restriction. However, due to the considerable variability in individuals' responses to reduced calories, the researchers initiated this project to understand the reasons behind these diverse responses.

The study involved examining approximately 200 strains of flies with distinct genetic backgrounds. These flies were raised on either a normal diet or one with dietary restriction, equivalent to only 10% of normal nutrition. The researchers identified five genes, including OXR1, with specific variants significantly influencing longevity under dietary restriction. Notably, two of these genes had human counterparts.

The chosen gene for in-depth exploration, referred to as "mustard" (mtd) in fruit flies and "Oxidation Resistance 1" (OXR1) in humans and mice, was

In a quest to understand the influence of a gene active in neurons on overall lifespan, a team conducted a series of thorough tests. Their findings revealed a connection between the OXR1 gene and a crucial cellular process known as the retromer, which consists of proteins essential for recycling cellular proteins and lipids.

The retromer plays a pivotal role in neurons as it dictates the destiny of all proteins entering the cell," explained Wilson.

Dysfunction in the retromer has been linked to age-related neurodegenerative diseases, such as Alzheimer's and Parkinson's, particularly those shielded by dietary restriction.

The study unfolds the narrative of how dietary restriction retards brain aging through the influence of mtd/OXR1 in preserving the retromer.

This research underscores the significance of the retromer pathway, which engages in reusing cellular proteins, in shielding neurons under nutrient constraints," noted Kapahi.

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