In a groundbreaking study led by Professor Pankaj Kapahi and postdoc Kenneth Wilson from the Buck Institute, the protective effects of dietary restriction on the brain have been attributed to the OXR1 gene. While the health and lifespan benefits of calorie restriction are well-established, this research sheds light on the crucial role of OXR1 in regulating these protective effects specifically within the brain.
Previously, calorie restriction was primarily associated with impacts on the digestive tract or fat accumulation. However, the study reveals that OXR1, active in the brain, contributes significantly to the observed extension of lifespan resulting from dietary restriction.
Key Player in Healthy Brain Aging
Known as “mustard” (mtd) in fruit flies and “Oxidation Resistance 1” (OXR1) in humans and mice, this gene has been identified as a key factor in promoting healthy aging within the brain. By investigating cellular mechanisms in fruit flies and human cells, the researchers unveiled a neuron-specific response responsible for the neuroprotection linked to dietary restriction, offering a potential avenue for therapeutic interventions in aging and age-related neurodegenerative diseases.
The Research Study
To comprehend the diverse responses to dietary restriction, approximately 200 fly strains with different genetic backgrounds were examined. Two genes, including OXR1, were pinpointed as having significant variants influencing longevity under dietary restriction. The loss of OXR1 in humans has been linked to severe neurological defects and premature death, while mice with extra OXR1 displayed improved survival in an amyotrophic lateral sclerosis (ALS) model.
The Complex Mechanisms of OXR1
The study delved into the intricate workings of OXR1 and its impact on a cellular complex called the retromer, 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, conditions that are alleviated by dietary restriction.
Dietary Restriction and the Aging Brain
The research underscores how dietary restriction slows brain aging through OXR1’s action in preserving retromer function. Kenneth Wilson explained, “Diet is influencing this gene. By eating less, you are enhancing this mechanism of proteins being sorted properly in your cells because your cells are enhancing the expression of OXR1.”
Increasing Lifespan through OXR1
The researchers observed that elevating mtd/OXR1 in flies resulted in a longer lifespan, suggesting potentially parallel effects in humans. The next phase involves identifying specific compounds that can increase OXR1 levels during aging, with the goal of delaying brain aging.
Implications for Health and Longevity
This groundbreaking research underscores the profound impact of diet on brain health and longevity. Professor Kenneth Wilson emphasized, “Diet impacts all the processes in your body. I think this work supports efforts to follow a healthy diet because what you eat will affect more than you know.”
With identified therapeutic targets, the study opens new frontiers for comprehending the complexities of brain aging and neuroprotection.