Scientists at the Buck Institute for Research on Aging have made a groundbreaking discovery in the realm of dietary restriction and its effects on aging, particularly in the brain.
Their study, published in Nature Communications, highlights the significant role of a gene called OXR1 in prolonging lifespan and ensuring healthy brain aging.
Kenneth Wilson, Ph.D., a Buck postdoc and the first author of the study, emphasizes the common misconception that dietary restriction primarily impacts the digestive tract or fat storage, overlooking its profound effects on the brain.
This research shifts the focus to the brain, spotlighting the OXR1 gene’s crucial role.
The team’s research, conducted on fruit flies and human cells, reveals how dietary restriction can delay aging and slow down neurodegenerative diseases’ progression.
They identified a neuron-specific response that mediates the neuroprotective effects of dietary restriction, suggesting that strategies like intermittent fasting might enhance OXR1 gene levels to offer this protection.
“The gene is an important brain resilience factor protecting against aging and neurological diseases,” notes Buck Professor Lisa Ellerby, Ph.D., co-senior author of the study.
The research began with examining about 200 strains of fruit flies on normal and restricted diets, leading to the identification of five genes with significant impacts on longevity under dietary restriction.
Two of these genes have human counterparts, with the team choosing to focus on the “mustard” (mtd) gene in fruit flies and “Oxidation Resistance 1” (OXR1) in humans and mice.
OXR1 is known to protect cells from oxidative damage, with its loss in humans resulting in severe neurological defects and premature death. Conversely, extra OXR1 in mice improves survival in amyotrophic lateral sclerosis (ALS) models.
The study explored how OXR1 impacts the retromer, a protein complex crucial for recycling cellular proteins and lipids.
Dysfunctions in the retromer are linked to age-related neurodegenerative diseases like Alzheimer’s and Parkinson’s, which are mitigated by dietary restriction.
The researchers discovered that mtd/OXR1 maintains retromer function, necessary for neuronal health, brain aging, and lifespan extension under dietary restriction.
“Diet is influencing this gene. By eating less, you are actually enhancing this mechanism of proteins being sorted properly in your cells,” explains Wilson.
This research opens new avenues for aging and brain health, suggesting that enhancing OXR1 levels could be a potential strategy to extend lifespan and delay brain aging.
It underscores the broader impacts of diet on bodily processes, reinforcing the importance of healthy eating habits for more than just physical health, but for brain health and longevity as well.
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The research findings can be found in Nature Communications.
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