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California, January 17, 2024
A recent study conducted by scientists at the Buck Institute for Research on Ageing in California has uncovered a crucial link between dietary patterns, brain ageing, and lifespan extension. The study emphasizes the role of a gene called OXR1, which plays a significant part in the benefits of dietary restriction, such as intermittent fasting or calorie restriction, on both brain health and overall longevity. The findings, published in the journal Nature Communications, shed light on the importance of understanding the cellular mechanisms underlying the effects of dietary choices on ageing and neurodegenerative diseases.
The researchers at the Buck Institute delved into the intricate details of how dietary restriction impacts ageing and neurodegenerative diseases using fruit flies and human cells as models. The study not only identified the key gene, OXR1, but also revealed a neuron-specific response responsible for the neuroprotection associated with dietary restriction.
Kenneth Wilson, a postdoctoral student at the Institute, highlighted the surprising connection between dietary restriction and brain health: “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.”
The team’s investigation involved examining approximately 200 strains of fruit flies with varying genetic backgrounds. These flies were subjected to different diets – a normal diet and a dietary restriction that amounted to only 10% of normal nutrition. The loss of the OXR1 gene in humans was found to lead to severe neurological defects and premature death. In mice, an excess of OXR1 demonstrated improved survival in a model of amyotrophic lateral sclerosis (ALS).
The study also uncovered the intricate cellular mechanism through which OXR1 operates, influencing a complex called the retromer. The retromer is a set of proteins crucial for recycling cellular proteins and lipids. Dysfunction in the retromer has been associated with age-related neurodegenerative diseases like Alzheimer’s and Parkinson’s, both conditions protected by dietary restriction.
Professor Pankaj Kapahi from the Buck Institute highlighted the potential therapeutic implications of the findings: “Strategies such as intermittent fasting or caloric restriction, which limit nutrients, may enhance levels of this gene to mediate its protective effects.”
In essence, the study suggests that the OXR1 gene acts as a key player in maintaining neuronal function, supporting healthy brain ageing, and contributing to the lifespan extension observed with dietary restriction. The researchers believe that by understanding how diet influences the expression of OXR1, individuals may explore strategies to enhance the proper sorting of proteins in their cells, promoting overall cellular health and longevity.
