Scientists identify how dietary restriction slows brain aging and increases lifespan


According to an article on, Scientists at the Buck Institute have delved into the mechanisms behind the health benefits and increased lifespan associated with dietary restriction, focusing on the role of the OXR1 gene. While dietary restriction is known to improve health and longevity, its specific effects on the brain have remained largely mysterious. The researchers discovered that OXR1 plays a vital role in the extension of lifespan seen with dietary restriction, particularly in the context of healthy brain aging.

Kenneth Wilson, a Buck postdoc and the study’s first author, emphasized the significance of understanding the impact of dietary restriction on the brain, noting that people often consider its effects on the digestive tract or fat buildup rather than its influence on the brain. The study, published in Nature Communications, not only sheds light on the role of OXR1 in lifespan extension but also uncovers a detailed cellular mechanism through which dietary restriction can delay aging and slow the progression of neurodegenerative diseases.

The research, conducted using fruit flies and human cells, identifies a neuron-specific response that mediates the neuroprotection associated with dietary restriction. Pankaj Kapahi, a Buck Professor and co-senior author of the study, suggests that strategies like intermittent fasting or caloric restriction, which limit nutrients, may enhance levels of the OXR1 gene, thereby mediating protective effects. OXR1 is identified as a crucial brain resilience factor protecting against aging and neurological diseases, according to Lisa Ellerby, another co-senior author of the study.

To explore the variability in individuals’ responses to dietary restriction, the researchers scanned about 200 strains of flies with different genetic backgrounds, identifying five genes, including OXR1, that significantly affected longevity under dietary restriction. The study focuses on OXR1, also known as “mustard” (mtd) in fruit flies, which protects cells from oxidative damage. Loss of OXR1 in humans results in severe neurological defects and premature death, while extra OXR1 in mice improves survival in a model of amyotrophic lateral sclerosis (ALS).

The researchers also found that increasing mtd/OXR1 in flies extended their lifespan, suggesting that excess expression of OXR1 in humans might contribute to lifespan extension. The next step involves identifying specific compounds that can increase OXR1 levels during aging to delay brain aging. The study underscores the interconnectedness of diet and gene expression, emphasizing the broader impact of diet on various bodily processes. Overall, the research supports the idea that following a healthy diet can influence more than just physical health and may contribute to understanding why brains degenerate over time. The study was supported by funds from the National Institutes of Health (NIH), the Larry L. Hillblom Foundation, and the National Centers of Competence in Research (NCCR).

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