Unlocking the Mystery: How a Specific Gene Links Diet, Brain Health, and Longer Life
In a groundbreaking revelation, scientists at the Buck Institute in Novato, California, have unraveled the connection between the right diet, brain health, and increased lifespan. Their focus zeroes in on the OXR1 gene, shedding light on why caloric restriction can be a key factor in slowing brain aging and potentially extending one's life.
Kenneth Wilson, PhD, a postdoc at the Buck Institute and the first author of the study, emphasizes the unexpected importance of the OXR1 gene in the brain when people restrict their food intake. Contrary to common assumptions about diet impacting the digestive tract or fat accumulation, this gene emerges as a crucial player in brain health.
The research, conducted with fruit flies and human cells, unveils a specific cellular mechanism through which dietary restriction can not only delay aging but also slow the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's. At the core of this process is the OXR1 gene, acting as a guardian, protecting brain cells from aging and the onset of neurological disorders.
Buck Professor Pankaj Kapahi, PhD, co-senior author of the study, highlights the discovery of a neuron-specific response that mediates the neuroprotection observed in dietary restriction. Strategies like intermittent fasting or caloric restriction, which limit nutrients, may boost the levels of the OXR1 gene, thereby enhancing its protective effects.
"The gene is an important brain resilience factor protecting against aging and neurological diseases," adds Buck Professor Lisa Ellerby, PhD, co-senior author of the study.
The research journey commenced with the study of around 200 strains of fruit flies subjected to different diets. The identification of genetic variants, including the OXR1 gene (referred to as "mustard" or "mtd" in fruit flies), significantly influencing longevity under calorie-restricted diets was a pivotal discovery. The gene's role in shielding cells from oxidative damage, preventing severe neurological defects and premature death, became apparent.
Interestingly, the study reveals that the OXR1 gene influences a protein complex known as the retromer, crucial for recycling cellular proteins and lipids. Neurons heavily depend on the retromer to determine the fate of proteins brought into the cell, making it a key player in preventing age-related neurodegenerative diseases.
Wilson explains, "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."
Looking ahead, the researchers aim to identify compounds that can elevate OXR1 levels in humans, potentially serving as a mechanism to delay brain aging and extend lifespan. Wilson concludes, "Hopefully from this, we can get more of an idea of why our brains degenerate in the first place. 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."